Doxil® + Melphalan + Velcade (DMV) in Relapsed/Refractory Multiple Myeloma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00985907
First received: September 25, 2009
Last updated: October 2, 2012
Last verified: October 2012
  Purpose

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).


Condition Intervention Phase
Multiple Myeloma
Drug: Doxil, melphalan, bortezomib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Liposomal Doxorubicin (Doxil®)/Melphalan/Bortezomib (Velcade®) in Relapsed/Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • To evaluate the safety and tolerability of four dose levels of liposomal doxorubicin, melphalan, and bortezomib in patients with relapsed/refractory MM [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • To identify a maximum tolerated dose (MTD) of liposomal doxorubicin, melphalan, and bortezomib in patients with relapsed/refractory MM [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the efficacy of DMV using: the overall response rate, and the time to response, progression-free survival, and overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Tabulate all toxicities of DMV at the MTD by NCI criteria [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Enrollment: 13
Study Start Date: June 2004
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Doxil® + Melphalan + Velcade (DMV) Drug: Doxil, melphalan, bortezomib

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

Other Name: 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 zolendronic 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.

  1. If 0/3 experience DLT (as defined in attachment Section 6.0), the next three patients will be escalated by one dose level.
  2. 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..
  3. 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
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Disease Characteristics:

  1. Patient previously diagnosed with MM;
  2. 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 CR.

Patient Characteristics:

  1. 18 yrs or older
  2. Patient has given voluntary written informed consent.
  3. Unless post-menopausal or surgically sterilized, a female must be willing to use an acceptable method of birth control
  4. Male patient must agree to use an acceptable method for contraception for the duration of the study.
  5. ECOG Performance Status 0-2.
  6. Life expectancy is at least 3 months.
  7. • 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
    • 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
  • MI 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 LVEF less than 35% by 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00985907

Locations
United States, California
UCSF
San Francisco, California, United States, 94143
United States, New York
St. Vincent's Comprehensive Cancer Center
New York, New York, United States
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Thomas Martin, MD University of California, San Francisco
  More Information

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00985907     History of Changes
Other Study ID Numbers: 2408
Study First Received: September 25, 2009
Last Updated: October 2, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
myeloma
DMV

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Doxorubicin
Bortezomib
Melphalan
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Protease Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 28, 2014