Back to resultsDoxil® + Melphalan + Velcade (DMV) in Relapsed/Refractory Multiple Myeloma (DMV)
Primary Purpose
Multiple Myeloma, Patient Participation
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Doxil, melphalan, bortezomib
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring myeloma, DMV
Eligibility Criteria
Inclusion Criteria:
Disease Characteristics:
- Patient previously diagnosed with multiple myeloma; Durie-Salmon Stage I, II, or III based on standard criteria
- Progressive disease. For non-secretory multiple myeloma, progressive disease is defined as bone marrow biopsy with > 25% increase in plasma cells or an absolute increase of at least 10% over prior known level. Alternatively, development of new or worsening of existing lytic bone lesions or soft tissue plasmacytomas, or hypercalcemia (serum calcium >11.5 mg/dL), or relapse from complete response.
Patient Characteristics:
- 18 yrs or older
- Patient has given voluntary written informed consent.
- Unless post-menopausal or surgically sterilized, a female must be willing to use an acceptable method of birth control
- Male patient must agree to use an acceptable method for contraception for the duration of the study.
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
- Life expectancy is at least 3 months.
• Absolute Neutrophil Count (ANC) over 1,000/ul without the use of colony stimulating factors
- Platelets over 50,000/ul without transfusion support 7 days
- Bilirubin 2.0 mg/dl or less
- aspartate aminotransferase (AST) 4 times or less upper limit normal Prior Therapy for Multiple Myeloma: Patients must have had at least 2 prior therapeutic regimens
Exclusion Criteria:
- Pregnant or breast feeding
- History of allergic reaction to compounds containing boron or mannitol.
- Active uncontrolled viral (including HIV), bacterial, or fungal infection.
- Grade III or IV toxicity due to previous anti-neoplastic therapy
- More than Grade 2 motor or sensory neuropathy
- Myocardial infarction within 6 months of enrollment or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled arrhythmias, or electrocardiographic evidence of acute ischemia.
- For any patients whose lifetime cumulative doxorubicin dose exceeds 400mg/m2, patients with left ventricular ejection fraction (LVEF) less than 35% by multigated acquisition (MUGA) .
- Concurrent administration of liposomal doxorubicin, melphalan, and bortezomib (single or two drug combinations of these are permissible)
- Less than 3 weeks since most recent chemotherapy or concurrent chemotherapy
- Use of corticosteroids (mroe than 10 mg prednisone/day or equivalent)
Sites / Locations
- University of California, San Francisco
- St. Vincent's Comprehensive Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Doxil® + Melphalan + Velcade (DMV)
Arm Description
Outcomes
Primary Outcome Measures
Number of Participants With Dose Limiting Toxicities (DLT) (Phase 1)
Safety assessments will be evaluated as the proportion of patients experiencing the following: treatment-related grade 3 or higher toxicity (hematologic and nonhematologic) and treatment-related death.
Maximum Tolerated Dose (MTD) (Phase 1)
The MTD will be considered the dose below where <= 3 patients experience a DLT and the dose that two cycles can be given without meeting toxicity criteria.
Secondary Outcome Measures
Number of All Treatment-related Toxicities at the MTD (Phase 1)
NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3 will be used to determine all treatment related toxicities at the MTD. Participants entered at the MTD Dose level from the phase I portion of the study will also be included in this analysis
Overall Response Rate
At each cycle, participants will be assessed for treatment response: Complete Response (CR), Near CR(nCR), Partial Response (PR), Minimal Response (MR), Stable Disease (SD), or Progressive Disease (PD) on at least 2 measurements at minimum of a 4 week interval. The overall response rate will use the best response of CR, nCR, PR, MR, or SD. In order to qualify for responses, the following events may NOT have occurred - new/increased size of plasmacytomas or bone lesions, recurrence or persistence of hypercalcemia. Collapse of bony structure from previous disease will not constitute progression or failure to respond. Participants entered at the MTD Dose level from the phase I portion of the study will also be included in this analysis
Time to Response (Phase 2)
Efficacy of DMV as determined by time to first observed response. Participants entered at the MTD Dose level from the phase I portion of the study will also be included in this analysis
Progression-free Survival (Phase 2)
Efficacy of DMV as determined by progression free survival. Participants entered at the MTD Dose level from the phase I portion of the study will also be included in this analysis
Overall Survival (Phase 2)
Overall survival is defined as the amount of time from start of study therapy until death, or study completion. Participants entered at the MTD Dose level from the phase I portion of the study will also be included in this analysis
Full Information
NCT ID
NCT00985907
First Posted
September 25, 2009
Last Updated
June 4, 2020
Sponsor
University of California, San Francisco
1. Study Identification
Unique Protocol Identification Number
NCT00985907
Brief Title
Doxil® + Melphalan + Velcade (DMV) in Relapsed/Refractory Multiple Myeloma
Acronym
DMV
Official Title
Phase I/II Study of Liposomal Doxorubicin (Doxil®)/Melphalan/Bortezomib (Velcade®) in Relapsed/Refractory Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Terminated
Why Stopped
Low Accrual
Study Start Date
October 28, 2004 (Actual)
Primary Completion Date
October 7, 2008 (Actual)
Study Completion Date
January 12, 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The median overall survival (OS) of relapsed/refractory multiple myeloma (MM) is less than nine months. However, phase II data with the proteasome inhibitor bortezomib (Velcade®) has been heartening, with 35% overall response rates and median survival of 16 months. In-vitro data has shown that this agent dramatically increases the sensitivity to chemotherapeutic agents. Liposomal doxorubicin (Doxil), melphalan, and bortezomib all have different mechanisms of action and toxicity profiles. Clinical studies employing two drug combinations with these agents in patients with refractory MM have found favorable efficacy (nearly no progression of disease) and tolerance data. Thus, the investigators are initiating a phase I/II study to examine the safety and efficacy of combining all three agents into the regimen DMV (Doxil® + melphalan + Velcade).
Detailed Description
Dose Level 1: Doxil 10 mg/m2, Melphalan 5 mg/m2, Velcade 0.7 mg/m2
Dose Level 2: Doxil 10 mg/m2, Melphalan 10 mg/m2, Velcade 0.7 mg/m2
Dose Level 3: Doxil 20 mg/m2, Melphalan 10 mg/m2, Velcade 0.7 mg/m2
Dose Level 4: Doxil 20 mg/m2, Melphalan 10 mg/m2, Velcade 1.0 mg/m2
Adjunctive therapy with a bisphosphonate, either pamidronate or zoledronic acid, will be given monthly.
Dose Escalation Schedule: Dose escalation will occur only after patients have completed at least two cycles at a given dose level.
If 0/3 experience DLT (as defined in attachment Section 6.0), the next three patients will be escalated by one dose level.
If 1/3 experience DLT, 3 additional patients enrolled at this dose level.
If 0, 1, or 2 of these additional patients experience DLT (i.e. total 3/6), the dose will be escalated.
If 3/3 experience DLT (i.e. total 4/6) then the next lower dose will be considered the MTD..
If 2/3 experience DLT, 3 additional patients enrolled at this dose level.
If 0 or 1 of these additional patients experience DLT (i.e. total 3/6), the dose will be escalated.
If 2 or more/3 experience DLT (i.e. total more than 3/6) then the next lower dose level is MTD
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma, Patient Participation
Keywords
myeloma, DMV
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Doxil® + Melphalan + Velcade (DMV)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Doxil, melphalan, bortezomib
Other Intervention Name(s)
Doxil, melphalan, Velcade
Intervention Description
Doxil®: IV over 30-60 min, Day 1 q28d
Melphalan: IV over 30 min, Day 1 q28d
Velcade®: IV bolus, Day 1, 4, 8, 11 q28d
Dose Level 1: Doxil 10 mg/m2, Melphalan 5 mg/m2, Velcade 0.7 mg/m2
Dose Level 2: Doxil 10 mg/m2, Melphalan 10 mg/m2, Velcade 0.7 mg/m2
Dose Level 3: Doxil 20 mg/m2, Melphalan 10 mg/m2, Velcade 0.7 mg/m2
Dose Level 4: Doxil 20 mg/m2, Melphalan 10 mg/m2, Velcade 1.0 mg/m2
Primary Outcome Measure Information:
Title
Number of Participants With Dose Limiting Toxicities (DLT) (Phase 1)
Description
Safety assessments will be evaluated as the proportion of patients experiencing the following: treatment-related grade 3 or higher toxicity (hematologic and nonhematologic) and treatment-related death.
Time Frame
Up to 2 cycles of treatment, approximately 56 days
Title
Maximum Tolerated Dose (MTD) (Phase 1)
Description
The MTD will be considered the dose below where <= 3 patients experience a DLT and the dose that two cycles can be given without meeting toxicity criteria.
Time Frame
Up to 1 year
Secondary Outcome Measure Information:
Title
Number of All Treatment-related Toxicities at the MTD (Phase 1)
Description
NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3 will be used to determine all treatment related toxicities at the MTD. Participants entered at the MTD Dose level from the phase I portion of the study will also be included in this analysis
Time Frame
5 years
Title
Overall Response Rate
Description
At each cycle, participants will be assessed for treatment response: Complete Response (CR), Near CR(nCR), Partial Response (PR), Minimal Response (MR), Stable Disease (SD), or Progressive Disease (PD) on at least 2 measurements at minimum of a 4 week interval. The overall response rate will use the best response of CR, nCR, PR, MR, or SD. In order to qualify for responses, the following events may NOT have occurred - new/increased size of plasmacytomas or bone lesions, recurrence or persistence of hypercalcemia. Collapse of bony structure from previous disease will not constitute progression or failure to respond. Participants entered at the MTD Dose level from the phase I portion of the study will also be included in this analysis
Time Frame
Up to 5 years
Title
Time to Response (Phase 2)
Description
Efficacy of DMV as determined by time to first observed response. Participants entered at the MTD Dose level from the phase I portion of the study will also be included in this analysis
Time Frame
28 days
Title
Progression-free Survival (Phase 2)
Description
Efficacy of DMV as determined by progression free survival. Participants entered at the MTD Dose level from the phase I portion of the study will also be included in this analysis
Time Frame
Up to 5 years
Title
Overall Survival (Phase 2)
Description
Overall survival is defined as the amount of time from start of study therapy until death, or study completion. Participants entered at the MTD Dose level from the phase I portion of the study will also be included in this analysis
Time Frame
Up to 5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Disease Characteristics:
Patient previously diagnosed with multiple myeloma; Durie-Salmon Stage I, II, or III based on standard criteria
Progressive disease. For non-secretory multiple myeloma, progressive disease is defined as bone marrow biopsy with > 25% increase in plasma cells or an absolute increase of at least 10% over prior known level. Alternatively, development of new or worsening of existing lytic bone lesions or soft tissue plasmacytomas, or hypercalcemia (serum calcium >11.5 mg/dL), or relapse from complete response.
Patient Characteristics:
18 yrs or older
Patient has given voluntary written informed consent.
Unless post-menopausal or surgically sterilized, a female must be willing to use an acceptable method of birth control
Male patient must agree to use an acceptable method for contraception for the duration of the study.
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
Life expectancy is at least 3 months.
• Absolute Neutrophil Count (ANC) over 1,000/ul without the use of colony stimulating factors
Platelets over 50,000/ul without transfusion support 7 days
Bilirubin 2.0 mg/dl or less
aspartate aminotransferase (AST) 4 times or less upper limit normal Prior Therapy for Multiple Myeloma: Patients must have had at least 2 prior therapeutic regimens
Exclusion Criteria:
Pregnant or breast feeding
History of allergic reaction to compounds containing boron or mannitol.
Active uncontrolled viral (including HIV), bacterial, or fungal infection.
Grade III or IV toxicity due to previous anti-neoplastic therapy
More than Grade 2 motor or sensory neuropathy
Myocardial infarction within 6 months of enrollment or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled arrhythmias, or electrocardiographic evidence of acute ischemia.
For any patients whose lifetime cumulative doxorubicin dose exceeds 400mg/m2, patients with left ventricular ejection fraction (LVEF) less than 35% by multigated acquisition (MUGA) .
Concurrent administration of liposomal doxorubicin, melphalan, and bortezomib (single or two drug combinations of these are permissible)
Less than 3 weeks since most recent chemotherapy or concurrent chemotherapy
Use of corticosteroids (mroe than 10 mg prednisone/day or equivalent)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Martin, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
St. Vincent's Comprehensive Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10011
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Doxil® + Melphalan + Velcade (DMV) in Relapsed/Refractory Multiple Myeloma
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