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

NCT00985907 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: 04262NCI-2011-01238
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

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).

Conditions

Multiple Myeloma; Patient Participation

Keywords

myeloma; DMV

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to 2 cycles of treatment, approximately 56 days

• 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.

  Up to 1 year

Secondary Outcomes (5)

• Number of All Treatment-related Toxicities at the MTD (Phase 1)

  5 years

• Overall Response Rate

  Up to 5 years

• Time to Response (Phase 2)

  28 days

• Progression-free Survival (Phase 2)

  Up to 5 years

• Overall Survival (Phase 2)

  Up to 5 years

Study Arms (1)

Doxil® + Melphalan + Velcade (DMV)

EXPERIMENTAL

Drug: Doxil, melphalan, bortezomib

Interventions

Doxil, melphalan, bortezomib DRUG

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

Also known as: Doxil, melphalan, Velcade

Doxil® + Melphalan + Velcade (DMV)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (2)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

St. Vincent's Comprehensive Cancer Center

New York, New York, 10011, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Patient Participation; Neoplasms, Plasma Cell

Interventions

liposomal doxorubicin; Melphalan; Bortezomib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Enrollment was terminated early due to low accrual in Phase 1. No participants were enrolled in Phase 2. Participant flow, baseline, and adverse event data was electronically transferred from a legacy clinical trials database by phase group only.

Results Point of Contact

• Title: Dr. Thomas Martin, MD
• Organization: University of California, San Francisco

Tom.Martin@ucsf.edu

(415) 353-9365

Study Officials

• Thomas Martin, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2009
• First Posted: September 29, 2009
• Study Start: October 28, 2004
• Primary Completion: October 7, 2008
• Study Completion: January 12, 2010
• Last Updated: June 17, 2020
• Results First Posted: June 17, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)