TerminatedNCT00985907DMVUpdated Jun 17, 2020Results posted

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

A Phase 1/2 interventional study of Doxil, melphalan, bortezomib in Multiple Myeloma and Patient Participation, sponsored by University of California, San Francisco. Terminated at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-06-17.

Sponsored by University of California, San Francisco · Phase 1/2, Interventional, and Treatment

Why this study was terminated

Low Accrual

From the registry’s dates

Registered 4 years 10 months after the study started (first participant enrolled Oct 2004, registered Sep 2009).

Phase: Phase 1/2
Study type: Interventional
Enrollment: 13
Allocation: Not applicable
Ages: 18 Years and older
Sex: All

Study 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).

Read the 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

Conditions studied

Multiple Myeloma
Patient Participation

Browse trials for

Keywords

myeloma
DMV

In context

Multiple Myeloma

3,632 studies on the registry are indexed under Multiple Myeloma; 745 are open to participants now.

This study's enrollment of 13 is below the median of 41 across 2,907 interventional studies indexed under Multiple Myeloma.

Browse Multiple Myeloma studies →

Lead sponsor

University of California, San Francisco is the lead sponsor of 2,132 studies on the registry; 375 are open to participants now.

Of its 262 completed or terminated interventional studies of FDA-regulated products, 196 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

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

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)

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 13 participants (actual)

Study arms

Experimental
Doxil® + Melphalan + Velcade (DMV)
Drug: Doxil, melphalan, bortezomib

Interventions

DrugDoxil, 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
Also known as: Doxil, melphalan, Velcade

What researchers measure

Primary outcomes

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.
Time frame: 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.
Time frame: Up to 1 year

Secondary outcomes

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
Time frame: 5 years
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 frame: Up to 5 years
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
Time frame: 28 days
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
Time frame: Up to 5 years
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
Time frame: Up to 5 years

Results

Posted Jun 17, 2020

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.

Participant flow

Participant flow — Overall Study
Milestone	Phase 1
Started	13
Completed	0
Not completed	13

Outcome measures

PrimaryNumber 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.

Time frame:: Up to 2 cycles of treatment, approximately 56 days
Reported as:: Count of participants · Participants

Number of Participants With Dose Limiting Toxicities (DLT) (Phase 1)
Participants	Doxil® + Melphalan + Velcade (DMV)
Number of Participants With Dose Limiting Toxicities (DLT) (Phase 1)	0

PrimaryMaximum 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.

Time frame:: Up to 1 year