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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00560391




Registration number
NCT00560391
Ethics application status
Date submitted
16/11/2007
Date registered
19/11/2007
Date last updated
4/08/2016

Titles & IDs
Public title
Dasatinib in Combination With Revlimid (and Dexamethasone)
Scientific title
A Phase I Single Arm Dose Escalation Study of the Combination of Dasatinib (Sprycel®) With Lenalidomide (Revlimid®) and Dexamethasone in Subjects With Relapsed and/ or Refractory Multiple Myeloma
Secondary ID [1] 0 0
CA180-180
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Dasatinib, 70 mg + Lenalidomide, 15 mg + Dexamethasone, 40 mg
Treatment: Drugs - Dasatinib, 70 mg + Lenalidomide, 20 mg + Dexamethasone, 40 mg
Treatment: Drugs - Dasatinib, 100 mg + Lenalidomide, 20 mg + Dexamethasone, 40 mg
Treatment: Drugs - Dasatinib, 100 mg + Lenalidomide, 25 mg + Dexamethasone, 40 mg
Treatment: Drugs - Dasatinib, 140 mg + Lenalidomide, 25 mg + Dexamethasone, 40 mg

Experimental: Dasatinib, 70 mg + Lenalidomide, 15 mg + Dexamethasone, 40 mg - 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.

Experimental: Dasatinib, 70 mg + Lenalidomide, 20 mg + Dexamethasone, 40 mg - 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.

Experimental: Dasatinib, 100 mg + Lenalidomide, 20 mg + Dexamethasone, 40 mg - 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.

Experimental: Dasatinib, 100 mg + Lenalidomide, 25 mg + Dexamethasone, 40 mg - 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.

Experimental: Dasatinib, 140 mg + Lenalidomide, 25 mg + Dexamethasone, 40 mg - Participants received a combination of dasatinib, lenalidomide, and dexamethasone in varying doses in 28-day cycles.


Treatment: Drugs: Dasatinib, 70 mg + Lenalidomide, 15 mg + Dexamethasone, 40 mg
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.

Treatment: Drugs: Dasatinib, 70 mg + Lenalidomide, 20 mg + Dexamethasone, 40 mg
Participants received dasatinib, 70 mg QD, for 28 days plus lenalidomide, 20 mg QD, for 21 days, plus dexamethasone, 40 mg QD, weekly on Days 1, 8, 15, and 22.

Treatment: Drugs: Dasatinib, 100 mg + Lenalidomide, 20 mg + Dexamethasone, 40 mg
Participants received dasatinib, 100 mg QD, for 28 days, plus lenalidomide, 20 mg QD, for 21 days, plus dexamethasone, 40 mg QD, weekly on Days 1, 8, 15, and 22.

Treatment: Drugs: Dasatinib, 100 mg + Lenalidomide, 25 mg + Dexamethasone, 40 mg
Participants received dasatinib, 100 mg QD, for 28 days, plus lenalidomide, 25 mg QD, for 21 days, plus dexamethasone, 40 mg QD, weekly on Days 1, 8, 15, and 22.

Treatment: Drugs: Dasatinib, 140 mg + Lenalidomide, 25 mg + Dexamethasone, 40 mg
Participants received dasatinib, 140 mg QD, for 28 days, plus lenalidomide, 25 mg QD, for 21 days, plus dexamethasone, 40 mg QD, weekly on Days 1, 8, 15, and 22. Cohort includes 4 participants who received treatment during the dose-finding phase and 13 participants who received treatment in the dose-expansion phase.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Recommended Phase II Dose (RP2D) of the Combination (Dasatinib + Lenalidomide + Dexamethasone)
Timepoint [1] 0 0
From the date of first dose to end of treatment (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]).
Primary outcome [2] 0 0
Number of Participants With Dose-limiting Toxicity (DLT)
Timepoint [2] 0 0
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]).
Primary outcome [3] 0 0
Number of Participants in the Dose Escalation Phase Who Reached Maximum Tolerated Dose (MTD) of Dasatinib With Lenalidomide and Dexamethasone
Timepoint [3] 0 0
From the date of first dose to end of treatment (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]).
Primary outcome [4] 0 0
Number of Participants Who Died, Serious Adverse Events (SAEs), Adverse Events (AEs) and AEs Leading to Study Drug Discontinuation
Timepoint [4] 0 0
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]).
Primary outcome [5] 0 0
Number of Participants With Hematology Abnormalities (Worst On-study Grade vs Baseline): Leukopenia, Neutropenia, Thrombocytopenia, and Anemia
Timepoint [5] 0 0
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])
Primary outcome [6] 0 0
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)
Timepoint [6] 0 0
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])
Primary outcome [7] 0 0
Number of Participants With Serum Chemistry Abnormalities (Worst On-study Grade vs Baseline): High Calcium, Low Calcium, Low Magnesium, and Low Phosphorus
Timepoint [7] 0 0
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 outcome [1] 0 0
Number of Participants With Complete Response and Very Good Partial Response
Timepoint [1] 0 0
Baseline, At the end of the treatment period (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]).
Secondary outcome [2] 0 0
Number of Participants With Partial Response
Timepoint [2] 0 0
Baseline, at the end of the treatment period (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]).
Secondary outcome [3] 0 0
Number of Participants With Minimal Response
Timepoint [3] 0 0
Baseline, at the end of the treatment period (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]).

Eligibility
Key inclusion criteria
* Able to provide written informed consent
* Men and women age = 18 years
* Confirmed diagnosis of multiple myeloma (MM) with measurable disease assessed within 1 month prior to treatment initiation
* Evidence of relapsed or refractory disease and at least one prior therapy for MM
* Eastern Cooperative Oncology Group Scale (ECOG) Performance Status of 0 - 2
* Last MM treatment at least 21 days prior to treatment initiation• Bone marrow transplant (BMT) at least 3 months prior to treatment initiation
* Required baseline hematology and chemistry parameters
* Resolution of acute toxicity due to prior therapy to Grade <2 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Women who are pregnant or breastfeeding
* Men whose sexual partners are women of child bearing potential (WOCBP) or WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least one month (4 weeks) before and for at least one month (4 weeks) after the last dose of study medication.
* Clinically significant cardiac disease (New York Heart Association [NYHA] Class III or IV)
* Abnormal corrected QT interval using Fridericia's formula (QTcF) interval prolonged (> 450 msec)
* Medications that are generally considered to have a risk of causing "Torsades de Pointes"
* Malabsorption syndrome or uncontrolled gastrointestinal toxicities
* Clinically significant pleural effusion in the previous 12 months or current ascites
* Clinically-significant coagulation or platelet function disorder
* Dementia, chronic medical or psychiatric condition, or laboratory abnormality
* Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality, serious uncontrolled medical disorder or active infection
* Intolerance to dasatinib and/or lenalidomide
* Subjects with a history of severe rash, hypersensitivity reaction or anaphylaxis related to prior thalidomide treatment

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/11/2012
Sample size
Target
Accrual to date
Final
35
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Local Institution - Prahran
Recruitment postcode(s) [1] 0 0
3181 - Prahran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
France
State/province [2] 0 0
Toulouse Cedex 03
Country [3] 0 0
France
State/province [3] 0 0
Vandoeuvre Les Nancy

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/study/NCT00560391
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00560391