Brief Summary

The purpose of this study was to determine the safety and tolerability of dasatinib when given in combination with lenalidomide and a low dose dexamethasone for the treatment of relapsed or refractory multiple myeloma.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P50-P75 for phase_1 multiple-myeloma

Timeline

Completed

Started May 2008

Typical duration for phase_1 multiple-myeloma

Geographic Reach

3 countries

4 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

4.5 years study duration

First Submitted

Initial submission to the registry

November 16, 2007

Completed

3 days until next milestone

First Posted

Study publicly available on registry

November 19, 2007

Completed

5 months until next milestone

Study Start

First participant enrolled

May 1, 2008

Completed

3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2011

Completed

10 months until next milestone

Results Posted

Study results publicly available

July 20, 2012

Completed

3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2012

Completed

Last Updated

August 4, 2016

Status Verified

November 1, 2013

Enrollment Period

3.4 years

First QC Date

November 16, 2007

Results QC Date

June 15, 2012

Last Update Submit

July 6, 2016

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (7)

Recommended Phase II Dose (RP2D) of the Combination (Dasatinib + Lenalidomide + Dexamethasone)
The RP2D was based on the MTD which was defined as the maximum combined dose producing dose limiting toxicity (DLT) in \< 33% of participants treated at the individual dose levels in the combination. The MTD is considered the last dose level combination tested just below the maximum administered dose (MAD) level combination and for which DLTs were observed in less than or equal to 33% of participants during the escalation and expansion phase. If MTD was not reached Please refer to Outcome Measure 2 for the complete definition of DLT.
From the date of first dose to end of treatment (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]).
Number of Participants With Dose-limiting Toxicity (DLT)
DLTs: At least possibly drug-related AEs occurring during the first cycle of treatment and are:GR4 neutropenia \>5 days/neutropenic fever;platelet count \<10000mm\^3 on \>1 occasion;GR4 fatigue,or 2-point decline in ECOG performance status;\>=GR3 nausea,diarrhea,and vomiting despite medical intervention;Any other clinically significant non-hematologic toxicity of \>=GR3 considered not related to underlying MM;Any GR3/4 laboratory abnormality requiring hospitalization;dose interruption of either dasatinib and/or lenalidomide for \>15 days due to any toxicity related to treatment with the combination.
From the date of first dose until at least 30 days after the last dose of study drug (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]).
Number of Participants in the Dose Escalation Phase Who Reached Maximum Tolerated Dose (MTD) of Dasatinib With Lenalidomide and Dexamethasone
The MTD is considered the last dose level combination tested just below the maximum administered dose (MAD) level combination and for which DLTs were observed in less than 33% of participants during the escalation and expansion phase. Please refer to outcome 2 for the complete definition of DLT. If the MTD was not reached at the highest dose administered as defined by protocol, the highest dose (dasatinib 140 mg QD + lenalidomide 25 mg QD) administered was selected for the dose expansion phase of the study.
From the date of first dose to end of treatment (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]).
Number of Participants Who Died, Serious Adverse Events (SAEs), Adverse Events (AEs) and AEs Leading to Study Drug Discontinuation
AE: New untoward medical occurrence or worsening of a preexisting medical condition that does not have causal relationship with this treatment. SAE: Untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, drug dependency/abuse; life-threatening, an important medical event, a congenital anomaly/birth defect; requires inpatient hospitalization/prolongs existing hospitalization. Grade 1= Mild; Grade 2= Moderate; Grade 3= Severe; Grade 4 = Life-threatening or disabling.
Baseline (pretreatment), from the date of first dose until at least 30 days after the last dose of study drug (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]).
Number of Participants With Hematology Abnormalities (Worst On-study Grade vs Baseline): Leukopenia, Neutropenia, Thrombocytopenia, and Anemia
As per NCI CTCAE Version 3.0 criteria. Grade (GR)1=Mild; GR2=Moderate; GR3=Severe; GR4=Life-threatening or disabling. White blood cell (WBC):GR1=\<LLN(lower limit of normal)-3.0\*10\^9/L; GR2=\<3.0-2.0\*10\^9/L; GR3:\<2.0-1.0\*10\^9/L; GR4:\<1.0\*10\^9/L. LLN=lower limit of normal. Absolute Neutrophil Count (ANC): GR1=\<LLN-1.5\*10\^9/L; GR2=\<1.5-1.0\*10\^9/L; GR3:\<1.0-0.5\*10\^9/L; GR4:\<0.5\*10\^9/L. Hemoglobin: GR1=\<LLN-10.0g/dL; GR2=\<10.0-8.0g/dL; GR3:\<8.0-6.5g/dL; GR4:\<6.5g/dL. Platelets: GR1=\<LLN-75.0\*10\^9/L; GR2=\<75.0-50.0\*10\^9/L; GR3:\<50.0-25.0\*10\^9/L; GR4:\<25.0\*10\^9/L. BL=Baseline; PBL=post baseline.
Baseline (pretreatment); Cycles 1 and 2 (within 24 hours of Days 1, 4, 8, 11, 15, 18, 21, and 25); beyond Cycle 2 (within 24 hours of Days 1 and 15,off treatment visit ) (median duration of dasatinib treatment=5.2 mo [range 0 to 33 mo])
Number of Participants With Serum Chemistry Abnormalities (Worst On-study Grade vs Baseline): Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Total Bilirubin (TB), and Serum Creatinine (SC)
Grading as per NCI CTCAE Version 3.0 criteria. GR1=Mild; GR2=Moderate; GR3=Severe; GR4=Life-threatening or disabling. Aspartate aminotransferase (AST) and alanine aminotransferase(ALT): GR1=\>ULN-2.5\*ULN (upper limit of normal); GR2=\>2.5-5.0\*ULN; GR3=\>5.0-20.0\*ULN; GR4:\>20.0\*ULN; TB:GR1=\>ULN-1.5\*ULN, GR2=\>1.5-3.0\*ULN, GR3=\>3-10\*ULN, GR4=\>10\*ULN; SC: GR1=\>ULN-1.5\*ULN, GR2=\>1.5-3.0\*ULN, GR3=\>3.0-6.0\*ULN, GR4=\>6.0\*ULN. BL=Baseline; PBL=post baseline.
Baseline (pretreatment); Cycles 1 and 2 (within 24 hours of Days 1, 4, 8, 11, 15, 18, 21, and 25); beyond Cycle 2 (within 24 hours of Days 1 and 15,off treatment visit ) (median duration of dasatinib treatment=5.2 mo [range 0 to 33 mo])
Number of Participants With Serum Chemistry Abnormalities (Worst On-study Grade vs Baseline): High Calcium, Low Calcium, Low Magnesium, and Low Phosphorus
Grading as per NCI CTCAE Version 3.0 criteria. GR1=Mild; GR2=Moderate; GR3=Severe; GR4=Life-threatening or disabling. Calcium (low): GR1: \<LLN - 8.0 mg/dL, GR2: \<8.0 - 7.0 mg/dL, GR3: \<7.0 - 6.0 mg/dL, GR4: \<6.0 mg/dL. Calcium (High): GR1: \>ULN - 11.5 mg/dL, GR2: \>11.5 - 12.5 mg/dL, GR3: \>12.5 - 13.5 mg/dL, GR4: \>13.5 mg/dL. Magnesium (Low): GR1: \<LLN - 1.2 mg/dL, GR2: \<1.2 - 0.9 mg/dL, GR3: \<0.9 - 0.7 mg/dL, GR4: \<0.7 mg/dL. Phosphorus (low): GR1: \<LLN - 2.5 mg/dL, GR2: \<2.5 - 2.0 mg/dL, GR3: \<2.0 - 1.0 mg/dL, GR4: \<1.0 mg/dL. BL=Baseline; PBL=post baseline.
Baseline (pretreatment); Cycles 1 and 2 (within 24 hours of Days 1, 4, 8, 11, 15, 18, 21, and 25); beyond Cycle 2 (within 24 hours of Days 1 and 15,off treatment visit ) (median duration of dasatinib treatment=5.2 mo [range 0 to 33 mo])

Secondary Outcomes (3)

Number of Participants With Complete Response and Very Good Partial Response
Baseline, At the end of the treatment period (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]).
Number of Participants With Partial Response
Baseline, at the end of the treatment period (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]).
Number of Participants With Minimal Response
Baseline, at the end of the treatment period (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]).

Study Arms (5)

Dasatinib, 70 mg + Lenalidomide, 15 mg + Dexamethasone, 40 mg

EXPERIMENTAL

Participants received a combination of dasatinib, 70 mg QD, lenalidomide, 15 mg QD, and dexamethasone, 40 mg QD, weekly on Days 1, 8, 15, and 22, in 28-day cycles.

Drug: Dasatinib, 70 mg + Lenalidomide, 15 mg + Dexamethasone, 40 mg

Dasatinib, 70 mg + Lenalidomide, 20 mg + Dexamethasone, 40 mg

EXPERIMENTAL

Participants received a combination of dasatinib, 70 mg QD, lenalidomide, 20 mg QD, and dexamethasone, 40 mg QD, weekly on Days 1, 8, 15, and 22, in 28-day cycles.

Drug: Dasatinib, 70 mg + Lenalidomide, 20 mg + Dexamethasone, 40 mg

Dasatinib, 100 mg + Lenalidomide, 20 mg + Dexamethasone, 40 mg

EXPERIMENTAL

Participants received a combination of dasatinib, 100 mg QD, lenalidomide, 20 mg QD, and dexamethasone, 40 mg QD, weekly on Days 1, 8, 15, and 22, in 28-day cycles.

Drug: Dasatinib, 100 mg + Lenalidomide, 20 mg + Dexamethasone, 40 mg

Dasatinib, 100 mg + Lenalidomide, 25 mg + Dexamethasone, 40 mg

EXPERIMENTAL

Participants received a combination of dasatinib, 100 mg QD, lenalidomide, 25 mg QD, and dexamethasone, 40 mg QD, weekly on Days 1, 8, 15, and 22, in 28-day cycles.

Drug: Dasatinib, 100 mg + Lenalidomide, 25 mg + Dexamethasone, 40 mg

Dasatinib, 140 mg + Lenalidomide, 25 mg + Dexamethasone, 40 mg

EXPERIMENTAL

Participants received a combination of dasatinib, lenalidomide, and dexamethasone in varying doses in 28-day cycles.

Drug: Dasatinib, 140 mg + Lenalidomide, 25 mg + Dexamethasone, 40 mg

Interventions

Dasatinib, 70 mg + Lenalidomide, 15 mg + Dexamethasone, 40 mgDRUG

Participants received dasatinib, 70 mg once daily (QD), for 28 days plus lenalidomide, 15 mg QD, for 21 days plus dexamethasone, 40 mg QD, weekly on Days 1, 8, 15, and 22.