Clinical trial NCT00843310: Combination of Revlimid, Melphalan and Dexamethasone as First Line Treatment for Multiple Myeloma
Official title: Phase II Study of Revlimid (Lenalidomide), Melphalan, and Dexamethasone (ReMeDex) for Newly Diagnosed Multiple Myeloma Patients Not Undergoing Autologous Transplantation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: multiple myeloma
frontline treatment
first-line treatment
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
Collaborators: name: Celgene
First posted: 2009-02-13
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
measure: Toxicity, Time to Progression & Progression Free Survival
timeFrame: every 28 days during therapy and every month after therapy for 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Bellevue Hospital
state: New York
city: New York
country: United States
facility: NYU Cancer Center
state: New York
city: New York
country: United States
facility: NYU Tisch Hospital
state: New York
Study officials:
affiliation: NYU Langone Health
name: Hearn J Cho, MD
role: PRINCIPAL_INVESTIGATOR
References: