Safety Study of Dasatinib With Bortezomib (Velcade®) and Dexamethasone for Multiple Myeloma

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Primary Purpose

Status

Terminated

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Dasatinib

Bortezomib

Dexamethasone

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

Confirmed diagnosis of multiple myeloma with measurable disease
Evidence of relapsed or refractory disease and at least 2 prior therapies for multiple myeloma
Eastern Cooperative Oncology Group Performance Status of 0 - 2
Last treatment for multiple myeloma not within 21 days prior to study treatment initiation
Bone marrow transplant not within 3 months prior to study treatment initiation
Required baseline hematology and chemistry parameters.

Key Exclusion Criteria:

Clinically significant cardiac disease (New York Heart Association Class III or IV)
Abnormal QT interval corrected for heart rate using Fridericia's formula prolonged (>450 msec) after electrolytes have been corrected on baseline electrocardiogram
Malabsorption syndrome or uncontrolled gastrointestinal toxicities
Dementia, chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation
Clinically significant pleural effusion in the previous 12 months or current ascites
Clinically significant coagulation or platelet function disorder
Intolerance to dasatinib and/or bortezomib
Acute diffuse infiltrative pulmonary disease
Prior or concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer, adequately treated Stage I or II cancer currently in complete remission, cervical carcinoma in situ, or any other cancer from which the participant has been disease-free for 3 years.

Sites / Locations

Orlando Health, Inc. M.D. Anderson Cancer Center Orlando
Winship Cancer Institute, Emory University
Local Institution
Local Institution
Local Institution
Local Institution
Local Institution

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dasatinib + Bortezomib + Dexamethasone

Arm Description

Phase I dose escalation study

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose (MTD) and Recommended MTD of Dasatinib in Combination With Bortezomib and Dexamethasone

MTD is defined as the dose level combination below the dose level that produces a dose-limiting toxicity in at least 2 out of 6 or fewer participants in that cohort. If MTD is not reached, the recommended MTD is the maximum dose that the participants received.

MTD and Recommended MTD of Bortezomib in Combination With Dasatinib and Dexamethasone

MTD is defined as the dose level combination below the dose level that produces a dose-limiting toxicity in at least 2 out of 6 or fewer participants in that cohort. If MTD is not reached, the recommended dose is the maximum dose that the participants received.

Secondary Outcome Measures

Best Overall Tumor Response Rate (RR) As Assessed Using International Uniform Response Criteria for Multiple Myeloma and Criteria of the European Bone Marrow Transplant Registry

S=serum; U=urine; MP=M-protein; ST=soft tissue, PC=plasmacytomas; IF=immunofixation; BL=baseline. RR calculated on best response any time. CR=MP undetectable by IF, ≤5% plasma cells in bone marrow, and no ST PC. VGPR=MP detectable by IF, or ≥90% drop in S MP and U MP<100 mg/24h. PR= ≥50% drop in S MP and ≥90% drop in U MP or U protein <200 mg/24h, ≥50% drop in BL ST PC size. MR= ≥25% to <50% drop in S MP and ≥50% to <90% drop in U MP and ≥25% to <50% drop in BL ST PC. SD=Not CR, VGPR, PR, or MR. PD= ≥25% rise in S or U M-component; new/increased size of bone lesions, ST PC, or hypercalcemia.

Duration of Response

Duration of response calculated for those with best response=CR (M-protein [MP] undetectable by immunofixation [IF], ≤5% plasma cells in bone marrow, no soft tissue plasmacytomas); VGPR (MP detectable by IF, or ≥90% drop in serum [S] MP and urine [U] MP<100 mg/24h); PR(≥50% drop in S MP and ≥90% drop in U MP or U protein <200 mg/24h, ≥50% drop in BL ST PC size); or MR (≥25% to <50% drop in S MP and ≥50% to <90% drop in U MP and ≥25% to <50% drop in BL ST PC). Duration of response calculated from day criteria for CR, VGPR, PR, and MR were met until progression or death, whichever came first.

Progression-free Survival

Progression-free survival was defined as the time from start of treatment until progression or death, whichever occurred first. Participants were to be followed-up for 12 months following the last dose of dasatinib for progression and survival. PFS was analyzed for the all-treated population.

Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, AEs, and Drug-related AEs by Grade

An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related=possibly, probably, or certainly related to or of unknown relationship to study treatment. Grade 3=severe; Grade 4=life-threatening.

Full Information

NCT ID

NCT00560352

First Posted

November 16, 2007

Last Updated

February 1, 2017

Sponsor

Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT00560352

Brief Title

Safety Study of Dasatinib With Bortezomib (Velcade®) and Dexamethasone for Multiple Myeloma

Official Title

A Phase I Study of Dasatinib With Bortezomib (Velcade®) and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

Study Type

Interventional

2. Study Status

Record Verification Date

July 2012

Overall Recruitment Status

Terminated

Study Start Date

February 2008 (undefined)

Primary Completion Date

February 2011 (Actual)

Study Completion Date

February 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

No

5. Study Description

Brief Summary

The purpose of this study is to determine the safety and tolerability of dasatinib with bortezomib in the treatment of relapsed or refractory multiple myeloma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

16 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dasatinib + Bortezomib + Dexamethasone

Arm Type

Experimental

Arm Description

Phase I dose escalation study

Intervention Type

Drug

Intervention Name(s)

Dasatinib

Other Intervention Name(s)

Sprycel, BMS-354825

Intervention Description

Tablets; oral; approximately 2 years on study, depending on response; 50 mg once daily (QD), 100 mg QD, 140 mg QD

Intervention Type

Drug

Intervention Name(s)

Bortezomib

Other Intervention Name(s)

Velcade®

Intervention Description

Powder; intravenous; approximately 2 years on study, depending on response; 1.0 mg/m^2 QD, 1.3 mg/m^2 QD

Intervention Type

Drug

Intervention Name(s)

Dexamethasone

Intervention Description

Tablets; oral; approximately 2 years on study, depending on response; 20 mg QD

Primary Outcome Measure Information:

Title

Maximum Tolerated Dose (MTD) and Recommended MTD of Dasatinib in Combination With Bortezomib and Dexamethasone

Description

MTD is defined as the dose level combination below the dose level that produces a dose-limiting toxicity in at least 2 out of 6 or fewer participants in that cohort. If MTD is not reached, the recommended MTD is the maximum dose that the participants received.

Time Frame

Days 1 to 21

Title

MTD and Recommended MTD of Bortezomib in Combination With Dasatinib and Dexamethasone

Description

MTD is defined as the dose level combination below the dose level that produces a dose-limiting toxicity in at least 2 out of 6 or fewer participants in that cohort. If MTD is not reached, the recommended dose is the maximum dose that the participants received.

Time Frame

Days 1 to 21

Secondary Outcome Measure Information:

Title

Best Overall Tumor Response Rate (RR) As Assessed Using International Uniform Response Criteria for Multiple Myeloma and Criteria of the European Bone Marrow Transplant Registry

Description

S=serum; U=urine; MP=M-protein; ST=soft tissue, PC=plasmacytomas; IF=immunofixation; BL=baseline. RR calculated on best response any time. CR=MP undetectable by IF, ≤5% plasma cells in bone marrow, and no ST PC. VGPR=MP detectable by IF, or ≥90% drop in S MP and U MP<100 mg/24h. PR= ≥50% drop in S MP and ≥90% drop in U MP or U protein <200 mg/24h, ≥50% drop in BL ST PC size. MR= ≥25% to <50% drop in S MP and ≥50% to <90% drop in U MP and ≥25% to <50% drop in BL ST PC. SD=Not CR, VGPR, PR, or MR. PD= ≥25% rise in S or U M-component; new/increased size of bone lesions, ST PC, or hypercalcemia.

Time Frame

Day 1 until last tumor assessment (maximum reached: 9 months)

Title

Duration of Response

Description

Duration of response calculated for those with best response=CR (M-protein [MP] undetectable by immunofixation [IF], ≤5% plasma cells in bone marrow, no soft tissue plasmacytomas); VGPR (MP detectable by IF, or ≥90% drop in serum [S] MP and urine [U] MP<100 mg/24h); PR(≥50% drop in S MP and ≥90% drop in U MP or U protein <200 mg/24h, ≥50% drop in BL ST PC size); or MR (≥25% to <50% drop in S MP and ≥50% to <90% drop in U MP and ≥25% to <50% drop in BL ST PC). Duration of response calculated from day criteria for CR, VGPR, PR, and MR were met until progression or death, whichever came first.

Time Frame

First occurrence of response to disease progression or death, whichever occurred first (maximum reached: 12.2 months)

Title

Progression-free Survival

Description

Progression-free survival was defined as the time from start of treatment until progression or death, whichever occurred first. Participants were to be followed-up for 12 months following the last dose of dasatinib for progression and survival. PFS was analyzed for the all-treated population.

Time Frame

Day 1 to disease progression or death, whichever came first (maximum reached: 14 months)

Title

Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, AEs, and Drug-related AEs by Grade

Description

An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related=possibly, probably, or certainly related to or of unknown relationship to study treatment. Grade 3=severe; Grade 4=life-threatening.

Time Frame

Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Key Inclusion Criteria: Confirmed diagnosis of multiple myeloma with measurable disease Evidence of relapsed or refractory disease and at least 2 prior therapies for multiple myeloma Eastern Cooperative Oncology Group Performance Status of 0 - 2 Last treatment for multiple myeloma not within 21 days prior to study treatment initiation Bone marrow transplant not within 3 months prior to study treatment initiation Required baseline hematology and chemistry parameters. Key Exclusion Criteria: Clinically significant cardiac disease (New York Heart Association Class III or IV) Abnormal QT interval corrected for heart rate using Fridericia's formula prolonged (>450 msec) after electrolytes have been corrected on baseline electrocardiogram Malabsorption syndrome or uncontrolled gastrointestinal toxicities Dementia, chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation Clinically significant pleural effusion in the previous 12 months or current ascites Clinically significant coagulation or platelet function disorder Intolerance to dasatinib and/or bortezomib Acute diffuse infiltrative pulmonary disease Prior or concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer, adequately treated Stage I or II cancer currently in complete remission, cervical carcinoma in situ, or any other cancer from which the participant has been disease-free for 3 years.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bristol-Myers Squibb

Organizational Affiliation

Bristol-Myers Squibb

Official's Role

Study Director

Facility Information:

Facility Name

Orlando Health, Inc. M.D. Anderson Cancer Center Orlando

City

Orlando

State/Province

Florida

ZIP/Postal Code

32806

Country

United States

Facility Name

Winship Cancer Institute, Emory University

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Facility Name

Local Institution

City

Nantes

State/Province

Cedex 1

ZIP/Postal Code

44093

Country

France

Facility Name

Local Institution

City

Lille Cedex

ZIP/Postal Code

59037

Country

France

Facility Name

Local Institution

City

Bari

ZIP/Postal Code

70124

Country

Italy

Facility Name

Local Institution

City

Bologna

ZIP/Postal Code

40138

Country

Italy

Facility Name

Local Institution

City

Salamanca

ZIP/Postal Code

37007

Country

Spain

Multiple Myeloma

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial