Clinical trial NCT00560391: Dasatinib in Combination With Revlimid (and Dexamethasone)
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2007-11-19
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

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

Primary outcomes:
measure: Recommended Phase II Dose (RP2D) of the Combination (Dasatinib + Lenalidomide + Dexamethasone)
timeFrame: From the date of first dose to end of treatment (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]).
measure: Number of Participants With Dose-limiting Toxicity (DLT)
timeFrame: 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]).
measure: Number of Participants in the Dose Escalation Phase Who Reached Maximum Tolerated Dose (MTD) of Dasatinib With Lenalidomide and Dexamethasone
timeFrame: From the date of first dose to end of treatment (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]).
measure: Number of Participants Who Died, Serious Adverse Events (SAEs), Adverse Events (AEs) and AEs Leading to Study Drug Discontinuation
timeFrame: 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]).
measure: Number of Participants With Hematology Abnormalities (Worst On-study Grade vs Baseline): Leukopenia, Neutropenia, Thrombocytopenia, and Anemia
timeFrame: 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])
measure: 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)
timeFrame: 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])
measure: Number of Participants With Serum Chemistry Abnormalities (Worst On-study Grade vs Baseline): High Calcium, Low Calcium, Low Magnesium, and Low Phosphorus
timeFrame: 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:
measure: Number of Participants With Complete Response and Very Good Partial Response
timeFrame: Baseline, At the end of the treatment period (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]).
measure: Number of Participants With Partial Response
timeFrame: Baseline, at the end of the treatment period (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]).
measure: Number of Participants With Minimal Response
timeFrame: Baseline, at the end of the treatment period (median duration of dasatinib treatment=5.2 months [range 0 to 33 months]).
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Prahran
country: Australia
facility: Local Institution
state: Victoria
city: Toulouse Cedex 03
country: France
facility: Local Institution
city: Vandoeuvre Les Nancy
country: France
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: