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Multiple MyelomaPhase 1/2DMVNCT00985907

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

A Phase 1/2 study testing Doxil, melphalan, bortezomib in people with Multiple Myeloma and Patient Participation, run by University of California, San Francisco at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma, Patient Participation
What is being tested?
Doxil, melphalan, bortezomib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
2 sitesUnited States
Study dates
28 Oct 2004to 12 Jan 2010
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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.
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  • 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)

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • St. Vincent's Comprehensive Cancer Center

    New York, New York, 10011

  • University of California, San Francisco

    San Francisco, California, 94143

Other trials in United States

About this study

Official title: Phase I/II Study of Liposomal Doxorubicin (Doxil®)/Melphalan/Bortezomib (Velcade®) in Relapsed/Refractory Multiple Myeloma

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.

  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..
  1. 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
Being tested
Doxil, melphalan, bortezomib
Keywords
myeloma, DMV
Medical subject headings
Multiple Myeloma, Patient Participation, Neoplasms, Plasma Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Doxil, melphalan, bortezomibDrug

    Also called Doxil, melphalan, Velcade

    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

Study groups in NCT00985907
Study groupRoleWhat they receive
Doxil® + Melphalan + Velcade (DMV)ExperimentalNot described
Receives: Drug: Doxil, melphalan, bortezomib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 2 cycles of treatment, approximately 56 days

  2. 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.

    Measured: Up to 1 year

Secondary outcomes (5)

  1. 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

    Measured: 5 years

  2. 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

    Measured: Up to 5 years

  3. 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

    Measured: 28 days

  4. 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

    Measured: Up to 5 years

  5. 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

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Sep 2009 (estimated)
  2. Study start28 Oct 2004
  3. Primary completion7 Oct 2008
  4. Study completion12 Jan 2010

Why it stopped: Low Accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00985907
Sponsor's protocol ID
04262
Other IDs
NCI-2011-01238
Acronym
DMV
Status last verified
Jun 2020
First submitted
25 Sep 2009
Last updated
17 Jun 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Doxil, melphalan, bortezomib in people with Multiple Myeloma and Patient Participation, run by University of California, San Francisco at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose Limiting Toxicities (DLT) (Phase 1) (time frame: Up to 2 cycles of treatment, approximately 56 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00985907.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2020.

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