Combination of Revlimid, Melphalan and Dexamethasone as First Line Treatment for Multiple Myeloma

June 21, 2017 updated by: NYU Langone Health

Phase II Study of Revlimid (Lenalidomide), Melphalan, and Dexamethasone (ReMeDex) for Newly Diagnosed Multiple Myeloma Patients Not Undergoing Autologous Transplantation

This study is to determine whether addition of Revlimid to standard therapy will increase overall and complete response rates compared to historical standard frontline therapy and whether this combination treatment has fewer side effects than similar combination induction treatment.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Current multiple myeloma therapies, typically an induction regimen followed by consolidation therapy with high dose chemotherapy and autologous stem cell rescue (autologous transplantation), can induce remission but relapse and death are inevitable. A growing body of literature suggests that consolidation therapy with autologous transplantation does not confer additional survival benefit and may have increased procedure-related morbidity and mortality in patients over 65 years old. Autologous transplantation is no longer recommended as standard care for this population. In addition, certain patients may not be eligible for autologous transplantation due to co-morbid medical conditions or may elect not to undergo the procedure for personal reasons.

The historic standard of care for multiple myeloma patients who were not eligible for autologous transplantation for consolidation was induction therapy with melphalan/ prednisone (MP), often followed by some form of maintenance therapy after achievement of complete or partial remission. A recent phase 3 study showed that the addition of thalidomide to MP (MPT) demonstrated higher overall and complete response rates. For patients who are eligible for autologous transplantation, thalidomide/ dexamethasone (Thal Dex) induction therapy is considered the standard of care, but a phase 2 study of lenalidomide (Revlimid)/ dexamethasone (Rev Dex) induction therapy demonstrated higher overall and complete response rates compared to Thal Dex. In addition, lenalidomide has a favorable side effect profile compared to thalidomide. Based on these data, we hypothesize that the combination of Revlimid/ melphalan/ dexamethasone (ReMeDex) induction therapy for myeloma patients who are not planned for autologous transplantation due to age restriction or other factors may demonstrate higher overall and/ or complete response rates with fewer side effects.

Study Type

Interventional

Enrollment (Actual)

8

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10016
        • Bellevue Hospital
      • New York, New York, United States, 10016
        • NYU Tisch Hospital
      • New York, New York, United States, 10016
        • NYU Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Newly Diagnosed multiple myeloma, ISS stage I-III requiring therapy: Serum M-protein ≥1 gm/dL (≥10 gm/L), Urine M-protein ≥200 mg/24 hr, Serum FLC assay: involved FLC ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal
  • Previously untreated except prior treatment with corticosteroid less than one full cycle of pulsed dose dexamethasone (40 mg daily days 1-4, 9-12, and 17-20) or equivalent is allowed. Concomitant administration of IV bisphosphonates, Zometa (zoledronic acid, up to 4 mg IVSS over 30 minutes every four weeks) or Aredia (alendronate, up to 90 mg IVSS over 4 hours every four weeks), for prophylaxis against skeletal complications due to lytic bone disease or for acute management of hypercalcemia is allowed. Concomitant external beam radiation therapy for local management of lytic bone disease is allowed.
  • Age ≥ 18 years old
  • Life expectancy ≥ 12 weeks
  • Eastern Cooperative Oncology Group (ECOG) Performance Status will be employed. ECOG 0-2 accepted.
  • WBC ≥ 3.0 X 103/ µL, ANC ≥ 1.5 X 103/ µl, Hgb ≥ 8.0 gm/ dL, Plt ≥ 75 X 103/ µl, Serum Creatinine ≤ 2.0 mg/ dL
  • Ability to understand and the willingness to sign a written informed consent document.
  • All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. See Appendix A: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.
  • Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).

Exclusion Criteria:

  • Prior therapy with Revlimid®, Thalomid (thalidomide), Velcade (bortezomib), Alkeran (melphalan) excluded. Prior therapy with corticosteroid allowed as defined in inclusion criteria.
  • No prior or concurrent treatment with an investigational agent.
  • Active Hepatitis B or C excluded, New York Heart Association grade III/IV congestive heart failure excluded, History of bleeding disorder excluded, History of platelet function disorder, History of deep vein thrombosis or other thromboembolic event excluded
  • Prior history of allergic reaction to IMiD™ compounds (Thalidomide, Lenalidomide) excluded.
  • Concomitant treatment with nonsteroidal antiinflammatory drugs (NSAIDs)(with the exception of aspirin) or other nephrotoxic agents is excluded.
  • Serum creatinine > 2.0 mg/ dL is excluded
  • Pregnancy and breastfeeding excluded
  • Known HIV+ patients are excluded.
  • Other active hematologic or solid tumor or history of such disease requiring therapy of any form within five years of screening is excluded.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ReMeDex

Treatment phase (28 days/cycle x 6 cycles):

Lenalidomide: 10 mg/day orally on days 1-21, followed by 7 days of rest. Melphalan: 4 mg/m2 daily on days 1-4. Dexamethasone: 40 mg daily on days 1, 8, 15 and 22.

Maintenance Phase (for subjects who achieve partial response or better at the end of the treatment phase):

lenalidomide: 10 mg/day orally on days 1-21 followed by 7 days of rest (28 days/cycle) for a maximum of 24 cycles.
Drug: Dexamethasone
Drug: Melphalan
Drug: Lenalidomide (Revlimid)
Other Names:
  • Revlimid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Toxicity, Time to Progression & Progression Free Survival
Time Frame: every 28 days during therapy and every month after therapy for 2 years

Toxicity will be scored using CTCAE version 3.0 for toxicity and adverse event reporting.

Progressive Disease: requires any one or more of the following:

  1. Increase of ≥25% from baseline in Serum M-component and/or (the absolute increase must be ≥0.5 g/dl)b
  2. Urine M-component and/or (the absolute increase must be ≥200 mg/24 h
  3. Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels. The absolute increase must be >10 mg/dl.
  4. Bone marrow plasma cell percentage: the absolute % must be ≥10%c
  5. Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas
  6. Development of hypercalcemia (corrected serum calcium >11.5 mg/dl or 2.65 mmol/l) that can be attributed solely to the plasma cell proliferative disorder
every 28 days during therapy and every month after therapy for 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NYU Langone Health

Collaborators

Celgene

Investigators

  • Principal Investigator: Hearn J Cho, MD, NYU Langone Health

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2008

Primary Completion (Actual)

October 1, 2011

Study Completion (Actual)

October 1, 2011

Study Registration Dates

First Submitted

February 12, 2009

First Submitted That Met QC Criteria

February 12, 2009

First Posted (Estimate)

February 13, 2009

Study Record Updates

Last Update Posted (Actual)

July 19, 2017

Last Update Submitted That Met QC Criteria

June 21, 2017

Last Verified

June 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 07-919
  • Celgene # RV-MM-PI-289 (Other Identifier: Celgene)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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