Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C14H19BCl2N2O4 |
Molecular Weight | 361.029 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(C)C[C@H](NC(=O)CNC(=O)C1=C(Cl)C=CC(Cl)=C1)B(O)O
InChI
InChIKey=MXAYKZJJDUDWDS-LBPRGKRZSA-N
InChI=1S/C14H19BCl2N2O4/c1-8(2)5-12(15(22)23)19-13(20)7-18-14(21)10-6-9(16)3-4-11(10)17/h3-4,6,8,12,22-23H,5,7H2,1-2H3,(H,18,21)(H,19,20)/t12-/m0/s1
DescriptionSources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208462lbl.pdfhttps://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208462s001lbl.pdf | http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003844/WC500217620.pdfCurator's Comment: description was created based on several sources, including
https://clinicaltrials.gov/ct2/show/NCT02630030 | https://www.ncbi.nlm.nih.gov/pubmed/24486586 | https://www.ncbi.nlm.nih.gov/pubmed/25016815 | https://www.ncbi.nlm.nih.gov/pubmed/25605842
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/208462lbl.pdfhttps://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208462s001lbl.pdf | http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003844/WC500217620.pdf
Curator's Comment: description was created based on several sources, including
https://clinicaltrials.gov/ct2/show/NCT02630030 | https://www.ncbi.nlm.nih.gov/pubmed/24486586 | https://www.ncbi.nlm.nih.gov/pubmed/25016815 | https://www.ncbi.nlm.nih.gov/pubmed/25605842
Ixazomib (MLN2238) is an active metabolite of orally bioavailable proteasome inhibitor ixazomib citrate (MLN9708), which hydrolyzes upon administration. Ixazomib citrate was approved under the name Ninlaro for the treatment of multiple myeloma in patients who have received at least one prior therapy. In vitro studies has shown that ixazomib preferentially binds and inhibits the chymotrypsin-like activity of the beta 5 subunit of the 20S proteasome.
CNS Activity
Sources: https://clinicaltrials.gov/ct2/show/NCT02630030http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003844/WC500217620.pdf
Curator's Comment: Following oral administration, a tissue distribution study in rats revealed that the brain and spinal cord were amongst the tissues with the lowest levels, suggesting that the penetration of ixazomib through the blood-brain barrier appears to be limited. However, the relevance to humans is unknown.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: P28074|||Q86T01 Gene ID: 5693.0 Gene Symbol: PSMB5 Target Organism: Homo sapiens (Human) |
0.93 nM [Ki] | ||
Target ID: P28074|||Q86T01 Gene ID: 5693.0 Gene Symbol: PSMB5 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/25605842 |
3.4 nM [IC50] | ||
Target ID: P49721 Gene ID: 5690.0 Gene Symbol: PSMB2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/25605842 |
3500.0 nM [IC50] | ||
Target ID: P20618 Gene ID: 5689.0 Gene Symbol: PSMB1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/25605842 |
31.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | NINLARO Approved UseNINLARO is a proteasome inhibitor indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. Launch Date1.44797755E12 |
|||
Primary | NINLARO Approved UseINDICATIONS AND USAGE. NINLARO is a proteasome inhibitor indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. Launch Date1.44797755E12 |
|||
Primary | NINLARO Approved UseINDICATIONS AND USAGE. NINLARO is a proteasome inhibitor indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. Launch Date1.44797755E12 |
|||
Primary | NINLARO Approved UseINDICATIONS AND USAGE. NINLARO is a proteasome inhibitor indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. Launch Date1.44797755E12 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
77 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26872892 |
4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered: |
IXAZOMIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
22.8 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26872892 |
4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered: |
IXAZOMIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT |
|
77 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26872892/ |
4 mg 3 times / 2 weeks multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
IXAZOMIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
25.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27196567/ |
3 mg single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered: |
IXAZOMIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
22.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26872892/ |
4 mg 3 times / 2 weeks multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
IXAZOMIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1470 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26872892 |
4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered: |
IXAZOMIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
999 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/26872892 |
4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered: |
IXAZOMIB blood | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT |
|
1470 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26872892/ |
4 mg 3 times / 2 weeks multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
IXAZOMIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
575 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27196567/ |
3 mg single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered: |
IXAZOMIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
999 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26872892/ |
4 mg 3 times / 2 weeks multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
IXAZOMIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: HIGH-FAT |
|
1161.92 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
1.33 mg/m^2 1 times / 3 days multiple, intravenous dose: 1.33 mg/m^2 route of administration: intravenous experiment type: multiple co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
1542.63999999999 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
1.76 mg/m^2 1 times / 3 days multiple, intravenous dose: 1.76 mg/m^2 route of administration: intravenous experiment type: multiple co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
191.87 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
1 mg/m^2 single, intravenous dose: 1 mg/m^2 route of administration: intravenous experiment type: single co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
301 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
0.5 mg/m^2 1 times / 3 days multiple, intravenous dose: 0.5 mg/m^2 route of administration: intravenous experiment type: multiple co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
3800 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
2.34 mg/m^2 1 times / 3 days multiple, intravenous dose: 2.34 mg/m^2 route of administration: intravenous experiment type: multiple co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
391.46 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
1.33 mg/m^2 single, intravenous dose: 1.33 mg/m^2 route of administration: intravenous experiment type: single co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
522.74 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
1.76 mg/m^2 single, intravenous dose: 1.76 mg/m^2 route of administration: intravenous experiment type: single co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
579.91 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
1 mg/m^2 1 times / 3 days multiple, intravenous dose: 1 mg/m^2 route of administration: intravenous experiment type: multiple co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
60.9 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
0.25 mg/m^2 1 times / 3 days multiple, intravenous dose: 0.25 mg/m^2 route of administration: intravenous experiment type: multiple co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
620 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
2.34 mg/m^2 single, intravenous dose: 2.34 mg/m^2 route of administration: intravenous experiment type: single co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
91.6 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
0.5 mg/m^2 single, intravenous dose: 0.5 mg/m^2 route of administration: intravenous experiment type: single co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
144.69 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
1.33 mg/m^2 1 times / 3 days multiple, intravenous dose: 1.33 mg/m^2 route of administration: intravenous experiment type: multiple co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
104.84 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
1.76 mg/m^2 1 times / 3 days multiple, intravenous dose: 1.76 mg/m^2 route of administration: intravenous experiment type: multiple co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
90.8 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
2.34 mg/m^2 1 times / 3 days multiple, intravenous dose: 2.34 mg/m^2 route of administration: intravenous experiment type: multiple co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
171.9 h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT00830869 |
1 mg/m^2 1 times / 3 days multiple, intravenous dose: 1 mg/m^2 route of administration: intravenous experiment type: multiple co-administered: |
IXAZOMIB plasma | Homo sapiens population: unhealthy age: Adults sex: food status: |
|
9.5 day EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28290121/ |
multiple, oral |
IXAZOMIB plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27196567/ |
3 mg single, oral dose: 3 mg route of administration: Oral experiment type: SINGLE co-administered: |
IXAZOMIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
1% |
IXAZOMIB plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
1.76 mg/m2 3 times / month multiple, intravenous Dose: 1.76 mg/m2, 3 times / month Route: intravenous Route: multiple Dose: 1.76 mg/m2, 3 times / month Sources: |
unhealthy, 45 years (range: 23–73 years) n = 7 Health Status: unhealthy Condition: non-hematologic malignancies Age Group: 45 years (range: 23–73 years) Sex: M+F Population Size: 7 Sources: |
DLT: Neutropenia... Dose limiting toxicities: Neutropenia (grade 4, 1 patient) Sources: |
3.11 mg/m2 3 times / month multiple, intravenous Highest studied dose Dose: 3.11 mg/m2, 3 times / month Route: intravenous Route: multiple Dose: 3.11 mg/m2, 3 times / month Sources: |
unhealthy, 56 years (range: 27–72 years) n = 5 Health Status: unhealthy Condition: non-hematologic malignancies Age Group: 56 years (range: 27–72 years) Sex: M+F Population Size: 5 Sources: |
DLT: Acute renal failure, Diarrhea... Dose limiting toxicities: Acute renal failure (grade 3, 1 patient) Sources: Diarrhea (grade 2-3, 2 patients) Vomiting (grade 2-3, 2 patients) Fatigue (grade 2, 1 patient) Nausea (grade 2, 1 patient) |
5.5 mg 3 times / month multiple, oral Highest studied dose Dose: 5.5 mg, 3 times / month Route: oral Route: multiple Dose: 5.5 mg, 3 times / month Sources: |
unhealthy, 66.0 years (range: 54–77 years) n = 5 Health Status: unhealthy Condition: relapsed or refractory light-chain (AL) amyloidosis Age Group: 66.0 years (range: 54–77 years) Sex: M+F Population Size: 5 Sources: |
DLT: Diarrhea, Renal failure... Dose limiting toxicities: Diarrhea (grade 3, 1 patient) Sources: Renal failure (grade 2, 1 patient) Failure respiratory (grade 2, 1 patient) |
4 mg 3 times / month multiple, oral MTD|RP2D|Recommended Dose: 4 mg, 3 times / month Route: oral Route: multiple Dose: 4 mg, 3 times / month Sources: |
unhealthy, 66.0 years (range: 54–77 years) n = 6 Health Status: unhealthy Condition: relapsed or refractory light-chain (AL) amyloidosis Age Group: 66.0 years (range: 54–77 years) Sex: M+F Population Size: 6 Sources: |
DLT: Thrombocytopenia... Dose limiting toxicities: Thrombocytopenia (grade 3, 1 patient) Sources: |
2.34 mg/m2 3 times / month multiple, intravenous MTD Dose: 2.34 mg/m2, 3 times / month Route: intravenous Route: multiple Dose: 2.34 mg/m2, 3 times / month Sources: |
unhealthy, 69.5 years (range: 47–75 years) n = 10 Health Status: unhealthy Condition: non-hematologic malignancies Age Group: 69.5 years (range: 47–75 years) Sex: M+F Population Size: 10 Sources: |
DLT: Neutropenia... Dose limiting toxicities: Neutropenia (grade 3, 1 patient) Sources: |
3.95 mg/m2 1 times / week multiple, oral Highest studied dose Dose: 3.95 mg/m2, 1 times / week Route: oral Route: multiple Dose: 3.95 mg/m2, 1 times / week Sources: |
unhealthy, 64.0 years (range: 40-76 years) n = 4 Health Status: unhealthy Condition: relapsed/refractory multiple myeloma Age Group: 64.0 years (range: 40-76 years) Sex: M+F Population Size: 4 Sources: |
DLT: Nausea, Vomiting... Dose limiting toxicities: Nausea (grade 3, 1 patient) Sources: Vomiting (grade 3, 1 patient) Diarrhea (grade 3, 1 patient) Erythema multiforme (grade 3, 1 patient) |
2.97 mg/m2 1 times / week multiple, oral MTD Dose: 2.97 mg/m2, 1 times / week Route: oral Route: multiple Dose: 2.97 mg/m2, 1 times / week Sources: |
unhealthy, 64.0 years (range: 40-76 years) Health Status: unhealthy Condition: relapsed/refractory multiple myeloma Age Group: 64.0 years (range: 40-76 years) Sex: M+F Sources: |
DLT: Nausea, Vomiting... Dose limiting toxicities: Nausea (grade 3, 1 patient) Sources: Vomiting (grade 3, 1 patient) Diarrhea (grade 3, 1 patient) |
4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Other AEs: Upper respiratory tract infection, Upper respiratory tract infection... Other AEs: Upper respiratory tract infection (grade 1-2, 19%) Sources: Upper respiratory tract infection (grade 3, <1%) Peripheral neuropathies (grade 1-2, 28%) Peripheral neuropathies (grade 3, 2%) Diarrhea (grade 1-2, 42%) Diarrhea (grade 3, 6%) Constipation (grade 1-2, 34%) Constipation (grade 3, <1%) Nausea (grade 1-2, 26%) Nausea (grade 3, 2%) Vomiting (grade 1-2, 22%) Vomiting (grade 3, 1%) Rash (grade 1-2, 19%) Rash (grade 3, 3%) Back pain (grade 1-2, 21%) Back pain (grade 3, <1%) Edema peripheral (grade 1-2, 25%) Edema peripheral (grade 3, 2%) Thrombocytopenia (grade 1-2, 78%) Thrombocytopenia (grade 3, 26%) Neutropenia (grade 1-2, 67%) Neutropenia (grade 3, 26%) Blurred vision (all grades, 3%) Dry eye (5%) Conjunctivitis (6%) |
4 mg 1 times / week multiple, oral MTD Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Sources: |
unhealthy, 66.0 years (range: 54–77 years) n = 6 Health Status: unhealthy Condition: relapsed/refractory AL amyloidosis Age Group: 66.0 years (range: 54–77 years) Sex: M+F Population Size: 6 Sources: |
DLT: Thrombocytopenia... Dose limiting toxicities: Thrombocytopenia (grade 3, 1 patient) Sources: |
5.5 mg 1 times / week multiple, oral Dose: 5.5 mg, 1 times / week Route: oral Route: multiple Dose: 5.5 mg, 1 times / week Sources: |
unhealthy, 66.0 years (range: 54–77 years) n = 5 Health Status: unhealthy Condition: relapsed/refractory AL amyloidosis Age Group: 66.0 years (range: 54–77 years) Sex: M+F Population Size: 5 Sources: |
DLT: Diarrhea, Renal failure... Dose limiting toxicities: Diarrhea (grade 3, 1 patient) Sources: Renal failure (grade 2, 1 patient) Dyspnea (grade 2, 1 patient) |
2.97 mg/m2 1 times / week multiple, oral Recommended Dose: 2.97 mg/m2, 1 times / week Route: oral Route: multiple Dose: 2.97 mg/m2, 1 times / week Co-administed with:: lenalidomide(25mg, PO, 1-21 day) Sources: Page: C16005dexamethasone(40mg, PO, 1-21 day, Days 1, 8, 15, 22) |
unhealthy, adult n = 31 Health Status: unhealthy Condition: cancer Age Group: adult Sex: M+F Population Size: 31 Sources: Page: C16005 |
Disc. AE: Thrombocytopenia, Diarrhea... Other AEs: Renal failure... AEs leading to discontinuation/dose reduction: Thrombocytopenia (1 patient) Other AEs:Diarrhea (1 patient) Nausea and vomiting (1 patient) Hypercalcemia (1 patient) Dyspnea (1 patient) Renal failure (2 patients) Sources: Page: C16005 |
4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: Page: p. 55dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy n = 360 Health Status: unhealthy Population Size: 360 Sources: Page: p. 55 |
Disc. AE: Diarrhea, Fatigue... AEs leading to discontinuation/dose reduction: Diarrhea Sources: Page: p. 55Fatigue (0.8%) Asthenia (0.8%) Peripheral sensory neuropathy (0.6%) Septic shock (0.6%) |
4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: Page: p. 56dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy n = 360 Health Status: unhealthy Population Size: 360 Sources: Page: p. 56 |
Disc. AE: Thrombocytopenia... AEs leading to discontinuation/dose reduction: Thrombocytopenia (8.6%) Sources: Page: p. 56 |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Neutropenia | grade 4, 1 patient DLT |
1.76 mg/m2 3 times / month multiple, intravenous Dose: 1.76 mg/m2, 3 times / month Route: intravenous Route: multiple Dose: 1.76 mg/m2, 3 times / month Sources: |
unhealthy, 45 years (range: 23–73 years) n = 7 Health Status: unhealthy Condition: non-hematologic malignancies Age Group: 45 years (range: 23–73 years) Sex: M+F Population Size: 7 Sources: |
Fatigue | grade 2, 1 patient DLT |
3.11 mg/m2 3 times / month multiple, intravenous Highest studied dose Dose: 3.11 mg/m2, 3 times / month Route: intravenous Route: multiple Dose: 3.11 mg/m2, 3 times / month Sources: |
unhealthy, 56 years (range: 27–72 years) n = 5 Health Status: unhealthy Condition: non-hematologic malignancies Age Group: 56 years (range: 27–72 years) Sex: M+F Population Size: 5 Sources: |
Nausea | grade 2, 1 patient DLT |
3.11 mg/m2 3 times / month multiple, intravenous Highest studied dose Dose: 3.11 mg/m2, 3 times / month Route: intravenous Route: multiple Dose: 3.11 mg/m2, 3 times / month Sources: |
unhealthy, 56 years (range: 27–72 years) n = 5 Health Status: unhealthy Condition: non-hematologic malignancies Age Group: 56 years (range: 27–72 years) Sex: M+F Population Size: 5 Sources: |
Diarrhea | grade 2-3, 2 patients DLT |
3.11 mg/m2 3 times / month multiple, intravenous Highest studied dose Dose: 3.11 mg/m2, 3 times / month Route: intravenous Route: multiple Dose: 3.11 mg/m2, 3 times / month Sources: |
unhealthy, 56 years (range: 27–72 years) n = 5 Health Status: unhealthy Condition: non-hematologic malignancies Age Group: 56 years (range: 27–72 years) Sex: M+F Population Size: 5 Sources: |
Vomiting | grade 2-3, 2 patients DLT |
3.11 mg/m2 3 times / month multiple, intravenous Highest studied dose Dose: 3.11 mg/m2, 3 times / month Route: intravenous Route: multiple Dose: 3.11 mg/m2, 3 times / month Sources: |
unhealthy, 56 years (range: 27–72 years) n = 5 Health Status: unhealthy Condition: non-hematologic malignancies Age Group: 56 years (range: 27–72 years) Sex: M+F Population Size: 5 Sources: |
Acute renal failure | grade 3, 1 patient DLT |
3.11 mg/m2 3 times / month multiple, intravenous Highest studied dose Dose: 3.11 mg/m2, 3 times / month Route: intravenous Route: multiple Dose: 3.11 mg/m2, 3 times / month Sources: |
unhealthy, 56 years (range: 27–72 years) n = 5 Health Status: unhealthy Condition: non-hematologic malignancies Age Group: 56 years (range: 27–72 years) Sex: M+F Population Size: 5 Sources: |
Failure respiratory | grade 2, 1 patient DLT, Disc. AE |
5.5 mg 3 times / month multiple, oral Highest studied dose Dose: 5.5 mg, 3 times / month Route: oral Route: multiple Dose: 5.5 mg, 3 times / month Sources: |
unhealthy, 66.0 years (range: 54–77 years) n = 5 Health Status: unhealthy Condition: relapsed or refractory light-chain (AL) amyloidosis Age Group: 66.0 years (range: 54–77 years) Sex: M+F Population Size: 5 Sources: |
Renal failure | grade 2, 1 patient DLT, Disc. AE |
5.5 mg 3 times / month multiple, oral Highest studied dose Dose: 5.5 mg, 3 times / month Route: oral Route: multiple Dose: 5.5 mg, 3 times / month Sources: |
unhealthy, 66.0 years (range: 54–77 years) n = 5 Health Status: unhealthy Condition: relapsed or refractory light-chain (AL) amyloidosis Age Group: 66.0 years (range: 54–77 years) Sex: M+F Population Size: 5 Sources: |
Diarrhea | grade 3, 1 patient DLT |
5.5 mg 3 times / month multiple, oral Highest studied dose Dose: 5.5 mg, 3 times / month Route: oral Route: multiple Dose: 5.5 mg, 3 times / month Sources: |
unhealthy, 66.0 years (range: 54–77 years) n = 5 Health Status: unhealthy Condition: relapsed or refractory light-chain (AL) amyloidosis Age Group: 66.0 years (range: 54–77 years) Sex: M+F Population Size: 5 Sources: |
Thrombocytopenia | grade 3, 1 patient DLT, Disc. AE |
4 mg 3 times / month multiple, oral MTD|RP2D|Recommended Dose: 4 mg, 3 times / month Route: oral Route: multiple Dose: 4 mg, 3 times / month Sources: |
unhealthy, 66.0 years (range: 54–77 years) n = 6 Health Status: unhealthy Condition: relapsed or refractory light-chain (AL) amyloidosis Age Group: 66.0 years (range: 54–77 years) Sex: M+F Population Size: 6 Sources: |
Neutropenia | grade 3, 1 patient DLT |
2.34 mg/m2 3 times / month multiple, intravenous MTD Dose: 2.34 mg/m2, 3 times / month Route: intravenous Route: multiple Dose: 2.34 mg/m2, 3 times / month Sources: |
unhealthy, 69.5 years (range: 47–75 years) n = 10 Health Status: unhealthy Condition: non-hematologic malignancies Age Group: 69.5 years (range: 47–75 years) Sex: M+F Population Size: 10 Sources: |
Diarrhea | grade 3, 1 patient DLT, Disc. AE |
3.95 mg/m2 1 times / week multiple, oral Highest studied dose Dose: 3.95 mg/m2, 1 times / week Route: oral Route: multiple Dose: 3.95 mg/m2, 1 times / week Sources: |
unhealthy, 64.0 years (range: 40-76 years) n = 4 Health Status: unhealthy Condition: relapsed/refractory multiple myeloma Age Group: 64.0 years (range: 40-76 years) Sex: M+F Population Size: 4 Sources: |
Erythema multiforme | grade 3, 1 patient DLT, Disc. AE |
3.95 mg/m2 1 times / week multiple, oral Highest studied dose Dose: 3.95 mg/m2, 1 times / week Route: oral Route: multiple Dose: 3.95 mg/m2, 1 times / week Sources: |
unhealthy, 64.0 years (range: 40-76 years) n = 4 Health Status: unhealthy Condition: relapsed/refractory multiple myeloma Age Group: 64.0 years (range: 40-76 years) Sex: M+F Population Size: 4 Sources: |
Nausea | grade 3, 1 patient DLT, Disc. AE |
3.95 mg/m2 1 times / week multiple, oral Highest studied dose Dose: 3.95 mg/m2, 1 times / week Route: oral Route: multiple Dose: 3.95 mg/m2, 1 times / week Sources: |
unhealthy, 64.0 years (range: 40-76 years) n = 4 Health Status: unhealthy Condition: relapsed/refractory multiple myeloma Age Group: 64.0 years (range: 40-76 years) Sex: M+F Population Size: 4 Sources: |
Vomiting | grade 3, 1 patient DLT, Disc. AE |
3.95 mg/m2 1 times / week multiple, oral Highest studied dose Dose: 3.95 mg/m2, 1 times / week Route: oral Route: multiple Dose: 3.95 mg/m2, 1 times / week Sources: |
unhealthy, 64.0 years (range: 40-76 years) n = 4 Health Status: unhealthy Condition: relapsed/refractory multiple myeloma Age Group: 64.0 years (range: 40-76 years) Sex: M+F Population Size: 4 Sources: |
Diarrhea | grade 3, 1 patient DLT, Disc. AE |
2.97 mg/m2 1 times / week multiple, oral MTD Dose: 2.97 mg/m2, 1 times / week Route: oral Route: multiple Dose: 2.97 mg/m2, 1 times / week Sources: |
unhealthy, 64.0 years (range: 40-76 years) Health Status: unhealthy Condition: relapsed/refractory multiple myeloma Age Group: 64.0 years (range: 40-76 years) Sex: M+F Sources: |
Nausea | grade 3, 1 patient DLT, Disc. AE |
2.97 mg/m2 1 times / week multiple, oral MTD Dose: 2.97 mg/m2, 1 times / week Route: oral Route: multiple Dose: 2.97 mg/m2, 1 times / week Sources: |
unhealthy, 64.0 years (range: 40-76 years) Health Status: unhealthy Condition: relapsed/refractory multiple myeloma Age Group: 64.0 years (range: 40-76 years) Sex: M+F Sources: |
Vomiting | grade 3, 1 patient DLT, Disc. AE |
2.97 mg/m2 1 times / week multiple, oral MTD Dose: 2.97 mg/m2, 1 times / week Route: oral Route: multiple Dose: 2.97 mg/m2, 1 times / week Sources: |
unhealthy, 64.0 years (range: 40-76 years) Health Status: unhealthy Condition: relapsed/refractory multiple myeloma Age Group: 64.0 years (range: 40-76 years) Sex: M+F Sources: |
Dry eye | 5% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Conjunctivitis | 6% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Blurred vision | all grades, 3% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Rash | grade 1-2, 19% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Upper respiratory tract infection | grade 1-2, 19% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Back pain | grade 1-2, 21% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Vomiting | grade 1-2, 22% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Edema peripheral | grade 1-2, 25% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Nausea | grade 1-2, 26% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Peripheral neuropathies | grade 1-2, 28% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Constipation | grade 1-2, 34% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Diarrhea | grade 1-2, 42% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Neutropenia | grade 1-2, 67% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Thrombocytopenia | grade 1-2, 78% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Vomiting | grade 3, 1% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Edema peripheral | grade 3, 2% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Nausea | grade 3, 2% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Peripheral neuropathies | grade 3, 2% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Neutropenia | grade 3, 26% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Thrombocytopenia | grade 3, 26% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Rash | grade 3, 3% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Diarrhea | grade 3, 6% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Back pain | grade 3, <1% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Constipation | grade 3, <1% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Upper respiratory tract infection | grade 3, <1% | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy, 66 years (range: 38 - 91 years) n = 360 Health Status: unhealthy Condition: relapsed and/or refractory multiple myeloma Age Group: 66 years (range: 38 - 91 years) Sex: M+F Population Size: 360 Sources: |
Thrombocytopenia | grade 3, 1 patient DLT, Disc. AE |
4 mg 1 times / week multiple, oral MTD Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Sources: |
unhealthy, 66.0 years (range: 54–77 years) n = 6 Health Status: unhealthy Condition: relapsed/refractory AL amyloidosis Age Group: 66.0 years (range: 54–77 years) Sex: M+F Population Size: 6 Sources: |
Dyspnea | grade 2, 1 patient DLT |
5.5 mg 1 times / week multiple, oral Dose: 5.5 mg, 1 times / week Route: oral Route: multiple Dose: 5.5 mg, 1 times / week Sources: |
unhealthy, 66.0 years (range: 54–77 years) n = 5 Health Status: unhealthy Condition: relapsed/refractory AL amyloidosis Age Group: 66.0 years (range: 54–77 years) Sex: M+F Population Size: 5 Sources: |
Renal failure | grade 2, 1 patient DLT |
5.5 mg 1 times / week multiple, oral Dose: 5.5 mg, 1 times / week Route: oral Route: multiple Dose: 5.5 mg, 1 times / week Sources: |
unhealthy, 66.0 years (range: 54–77 years) n = 5 Health Status: unhealthy Condition: relapsed/refractory AL amyloidosis Age Group: 66.0 years (range: 54–77 years) Sex: M+F Population Size: 5 Sources: |
Diarrhea | grade 3, 1 patient DLT, Disc. AE |
5.5 mg 1 times / week multiple, oral Dose: 5.5 mg, 1 times / week Route: oral Route: multiple Dose: 5.5 mg, 1 times / week Sources: |
unhealthy, 66.0 years (range: 54–77 years) n = 5 Health Status: unhealthy Condition: relapsed/refractory AL amyloidosis Age Group: 66.0 years (range: 54–77 years) Sex: M+F Population Size: 5 Sources: |
Diarrhea | 1 patient Disc. AE |
2.97 mg/m2 1 times / week multiple, oral Recommended Dose: 2.97 mg/m2, 1 times / week Route: oral Route: multiple Dose: 2.97 mg/m2, 1 times / week Co-administed with:: lenalidomide(25mg, PO, 1-21 day) Sources: Page: C16005dexamethasone(40mg, PO, 1-21 day, Days 1, 8, 15, 22) |
unhealthy, adult n = 31 Health Status: unhealthy Condition: cancer Age Group: adult Sex: M+F Population Size: 31 Sources: Page: C16005 |
Dyspnea | 1 patient Disc. AE |
2.97 mg/m2 1 times / week multiple, oral Recommended Dose: 2.97 mg/m2, 1 times / week Route: oral Route: multiple Dose: 2.97 mg/m2, 1 times / week Co-administed with:: lenalidomide(25mg, PO, 1-21 day) Sources: Page: C16005dexamethasone(40mg, PO, 1-21 day, Days 1, 8, 15, 22) |
unhealthy, adult n = 31 Health Status: unhealthy Condition: cancer Age Group: adult Sex: M+F Population Size: 31 Sources: Page: C16005 |
Hypercalcemia | 1 patient Disc. AE |
2.97 mg/m2 1 times / week multiple, oral Recommended Dose: 2.97 mg/m2, 1 times / week Route: oral Route: multiple Dose: 2.97 mg/m2, 1 times / week Co-administed with:: lenalidomide(25mg, PO, 1-21 day) Sources: Page: C16005dexamethasone(40mg, PO, 1-21 day, Days 1, 8, 15, 22) |
unhealthy, adult n = 31 Health Status: unhealthy Condition: cancer Age Group: adult Sex: M+F Population Size: 31 Sources: Page: C16005 |
Nausea and vomiting | 1 patient Disc. AE |
2.97 mg/m2 1 times / week multiple, oral Recommended Dose: 2.97 mg/m2, 1 times / week Route: oral Route: multiple Dose: 2.97 mg/m2, 1 times / week Co-administed with:: lenalidomide(25mg, PO, 1-21 day) Sources: Page: C16005dexamethasone(40mg, PO, 1-21 day, Days 1, 8, 15, 22) |
unhealthy, adult n = 31 Health Status: unhealthy Condition: cancer Age Group: adult Sex: M+F Population Size: 31 Sources: Page: C16005 |
Thrombocytopenia | 1 patient Disc. AE |
2.97 mg/m2 1 times / week multiple, oral Recommended Dose: 2.97 mg/m2, 1 times / week Route: oral Route: multiple Dose: 2.97 mg/m2, 1 times / week Co-administed with:: lenalidomide(25mg, PO, 1-21 day) Sources: Page: C16005dexamethasone(40mg, PO, 1-21 day, Days 1, 8, 15, 22) |
unhealthy, adult n = 31 Health Status: unhealthy Condition: cancer Age Group: adult Sex: M+F Population Size: 31 Sources: Page: C16005 |
Renal failure | 2 patients | 2.97 mg/m2 1 times / week multiple, oral Recommended Dose: 2.97 mg/m2, 1 times / week Route: oral Route: multiple Dose: 2.97 mg/m2, 1 times / week Co-administed with:: lenalidomide(25mg, PO, 1-21 day) Sources: Page: C16005dexamethasone(40mg, PO, 1-21 day, Days 1, 8, 15, 22) |
unhealthy, adult n = 31 Health Status: unhealthy Condition: cancer Age Group: adult Sex: M+F Population Size: 31 Sources: Page: C16005 |
Peripheral sensory neuropathy | 0.6% Disc. AE |
4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: Page: p. 55dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy n = 360 Health Status: unhealthy Population Size: 360 Sources: Page: p. 55 |
Septic shock | 0.6% Disc. AE |
4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: Page: p. 55dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy n = 360 Health Status: unhealthy Population Size: 360 Sources: Page: p. 55 |
Asthenia | 0.8% Disc. AE |
4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: Page: p. 55dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy n = 360 Health Status: unhealthy Population Size: 360 Sources: Page: p. 55 |
Fatigue | 0.8% Disc. AE |
4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: Page: p. 55dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy n = 360 Health Status: unhealthy Population Size: 360 Sources: Page: p. 55 |
Diarrhea | Disc. AE | 4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: Page: p. 55dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy n = 360 Health Status: unhealthy Population Size: 360 Sources: Page: p. 55 |
Thrombocytopenia | 8.6% Disc. AE |
4 mg 1 times / week multiple, oral Recommended Dose: 4 mg, 1 times / week Route: oral Route: multiple Dose: 4 mg, 1 times / week Co-administed with:: lenalidomide(25 mg on Days 1 throughn21) Sources: Page: p. 56dexamethasone(40 mg on Days 1, 8, 15, and 22 of a 28-day cycle) |
unhealthy n = 360 Health Status: unhealthy Population Size: 360 Sources: Page: p. 56 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Drug as perpetrator
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
major | ||||
minor | ||||
minor | ||||
minor | ||||
minor | ||||
no | ||||
weak | ||||
yes | unlikely Comment: Smoking is known to be a moderate CYP1A2 inducer. Based on population PK analyses of smokers in the Phase 3 Study C16010, smoking status (n=33 current smokers) was not found to be a significant covariate affecting ixazomib PK Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208462Orig1s000ClinPharmR.pdf#page=8 Page: 8.0 |
|||
yes | yes (co-administration study) Comment: Clinical DDI studies with strong CYP3A4 inhibitors ketoconazole and clarithromycin did not show clinically meaningful effects on ixazomib systemic exposure. On the other hand, clinical study with the strong CYP3A4 inducer rifampin showed significant decrease in ixazomib exposure (AUC v74%, CMAX |54%). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208462Orig1s000ClinPharmR.pdf#page=5 Page: 5.0 |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/208462Orig1s000PharmR.pdf#page=14 Page: 14.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Intracellular protein degradation: from a vague idea, through the lysosome and the ubiquitin-proteasome system, and onto human diseases and drug targeting (Nobel lecture). | 2005 Sep 19 |
|
Bortezomib-mediated 26S proteasome inhibition causes cell-cycle arrest and induces apoptosis in CD-30+ anaplastic large cell lymphoma. | 2007 Apr |
|
Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. | 2010 Mar 1 |
|
An evidence-based review of ixazomib citrate and its potential in the treatment of newly diagnosed multiple myeloma. | 2014 |
|
Ixazomib for the treatment of multiple myeloma. | 2015 |
|
The investigational proteasome inhibitor ixazomib for the treatment of multiple myeloma. | 2015 |
|
Therapeutic landscape of carfilzomib and other modulators of the ubiquitin-proteasome pathway. | 2015 Mar 1 |
Patents
Sample Use Guides
Recommended starting dose of 4 mg taken orally on Days 1, 8, and 15 of a 28-day cycle. Dose should be taken at least one hour before or at least two hours after food.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24486586
Osteoblasts were generated from mesenchymal osteoprogenitors by culture in osteogenic medium (containing 5 mmol/L b-glycerophosphate, 50 mkg/mL ascorbic acid, and 80 nmol/L dexamethasone). Mesenchymal stem cell (MSC, passage 2–3) or the hMSC–TERT cell line were exposed to different MLN2238 or bortezomib concentrations and cultured in osteogenic medium for 11 or 21 days for alkaline phosphatase (ALP) activity and matrix mineralization assays, respectively. ALP activity was quantified by hydrolysis of p-nitrophenylphosphate into p-nitrophenol (Sigma-Aldrich), whereas mineralization was assessed by quantitative measurement of Alizarin Red staining.
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C2160
Created by
admin on Sat Dec 17 00:07:08 UTC 2022 , Edited by admin on Sat Dec 17 00:07:08 UTC 2022
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WHO-ATC |
L01XX50
Created by
admin on Sat Dec 17 00:07:08 UTC 2022 , Edited by admin on Sat Dec 17 00:07:08 UTC 2022
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NDF-RT |
N0000175604
Created by
admin on Sat Dec 17 00:07:08 UTC 2022 , Edited by admin on Sat Dec 17 00:07:08 UTC 2022
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EU-Orphan Drug |
EU/3/12/1060
Created by
admin on Sat Dec 17 00:07:08 UTC 2022 , Edited by admin on Sat Dec 17 00:07:08 UTC 2022
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Code System | Code | Type | Description | ||
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5067
Created by
admin on Sat Dec 17 00:07:08 UTC 2022 , Edited by admin on Sat Dec 17 00:07:08 UTC 2022
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PRIMARY | |||
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25183872
Created by
admin on Sat Dec 17 00:07:08 UTC 2022 , Edited by admin on Sat Dec 17 00:07:08 UTC 2022
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PRIMARY | |||
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1072833-77-2
Created by
admin on Sat Dec 17 00:07:08 UTC 2022 , Edited by admin on Sat Dec 17 00:07:08 UTC 2022
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PRIMARY | |||
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Ixazomib
Created by
admin on Sat Dec 17 00:07:08 UTC 2022 , Edited by admin on Sat Dec 17 00:07:08 UTC 2022
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PRIMARY | |||
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1723735
Created by
admin on Sat Dec 17 00:07:08 UTC 2022 , Edited by admin on Sat Dec 17 00:07:08 UTC 2022
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PRIMARY | RxNorm | ||
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C97940
Created by
admin on Sat Dec 17 00:07:08 UTC 2022 , Edited by admin on Sat Dec 17 00:07:08 UTC 2022
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PRIMARY | |||
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DB09570
Created by
admin on Sat Dec 17 00:07:08 UTC 2022 , Edited by admin on Sat Dec 17 00:07:08 UTC 2022
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PRIMARY | |||
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SUB121332
Created by
admin on Sat Dec 17 00:07:08 UTC 2022 , Edited by admin on Sat Dec 17 00:07:08 UTC 2022
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PRIMARY | |||
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71050168A2
Created by
admin on Sat Dec 17 00:07:08 UTC 2022 , Edited by admin on Sat Dec 17 00:07:08 UTC 2022
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PRIMARY | |||
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71050168A2
Created by
admin on Sat Dec 17 00:07:08 UTC 2022 , Edited by admin on Sat Dec 17 00:07:08 UTC 2022
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PRIMARY | |||
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90942
Created by
admin on Sat Dec 17 00:07:08 UTC 2022 , Edited by admin on Sat Dec 17 00:07:08 UTC 2022
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PRIMARY | |||
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Ixazomib
Created by
admin on Sat Dec 17 00:07:08 UTC 2022 , Edited by admin on Sat Dec 17 00:07:08 UTC 2022
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PRIMARY | |||
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9411
Created by
admin on Sat Dec 17 00:07:08 UTC 2022 , Edited by admin on Sat Dec 17 00:07:08 UTC 2022
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PRIMARY | |||
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DTXSID701025662
Created by
admin on Sat Dec 17 00:07:08 UTC 2022 , Edited by admin on Sat Dec 17 00:07:08 UTC 2022
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PRIMARY | |||
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M11904
Created by
admin on Sat Dec 17 00:07:08 UTC 2022 , Edited by admin on Sat Dec 17 00:07:08 UTC 2022
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PRIMARY | |||
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YY-46
Created by
admin on Sat Dec 17 00:07:08 UTC 2022 , Edited by admin on Sat Dec 17 00:07:08 UTC 2022
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PRIMARY |
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