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

This study has been terminated.
(Due to slow accrual)
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT00843310
First received: February 12, 2009
Last updated: August 13, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: Lenalidomide (Revlimid)
Drug: Melphalan
Drug: Dexamethasone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Revlimid (Lenalidomide), Melphalan, and Dexamethasone (ReMeDex) for Newly Diagnosed Multiple Myeloma Patients Not Undergoing Autologous Transplantation

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • Overall and Complete Response Rates [ Time Frame: every 28 days during therapy and every month after therapy for 2 years ] [ Designated as safety issue: No ]

    Response rate is defined as the percentage of patients who achieved response out of the total enrolled patients. Response is evaluated using the International Uniform Response Criteria by the International Myeloma Working Group.

    Overall response = stringent complete response+complete response+very good partial response+partial response;

    Complete response = stringent complete response+complete response



Secondary Outcome Measures:
  • Drug Toxicity Rates [ Time Frame: during therapy and 30 days after ] [ Designated as safety issue: Yes ]
    Percentage of participantswho experienced an adverse event among the treated population.

  • Time to Progression [ Time Frame: every 28 days during therapy and every month after therapy for 2 years ] [ Designated as safety issue: No ]
    Progression of disease is evaluated using the International Uniform Response Criteria by the International Myeloma Working Group.

  • Progression Free Survival [ Time Frame: every 28 days during therapy and every month after therapy for 2 years ] [ Designated as safety issue: No ]

Enrollment: 8
Study Start Date: November 2008
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: Lenalidomide (Revlimid)
Other Name: Revlimid
Drug: Melphalan Drug: Dexamethasone

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.

  Eligibility

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

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.
  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: NCT00843310

Locations
United States, New York
NYU Cancer Center
New York, New York, United States, 10016
NYU Tisch Hospital
New York, New York, United States, 10016
Bellevue Hospital
New York, New York, United States, 10016
Sponsors and Collaborators
New York University School of Medicine
Celgene Corporation
Investigators
Principal Investigator: Hearn J Cho, MD New York University School of Medicine
  More Information

No publications provided

Responsible Party: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT00843310     History of Changes
Other Study ID Numbers: 07-919, Celgene # RV-MM-PI-289
Study First Received: February 12, 2009
Results First Received: August 13, 2013
Last Updated: August 13, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by New York University School of Medicine:
multiple myeloma
frontline treatment
first-line treatment

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
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Lenalidomide
Melphalan
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids

ClinicalTrials.gov processed this record on September 18, 2014