Melphalan, Prednisone, and Thalidomide or Lenalidomide in Treating Patients With Newly Diagnosed Multiple Myeloma
|Stage I Multiple Myeloma Stage II Multiple Myeloma Stage III Multiple Myeloma||Drug: melphalan Drug: prednisone Drug: thalidomide Drug: lenalidomide||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||An Intergroup Phase III Randomized Controlled Trial Comparing Melphalan, Prednisone and Thalidomide (MPT) Versus Melphalan, Prednisone and Lenalidomide (Revlimid™) (MPR) in Newly Diagnosed Multiple Myeloma Patients Who Are Not Candidates for High-Dose Therapy|
- Progression-Free Survival (PFS) [ Time Frame: Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually for 10 years from the date of randomization. ]PFS is defined as the time from randomization to the earlier of progression or death of any cause.
- Overall Survival [ Time Frame: Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually for 10 years from the date of randomization. ]Overall survival was defined as time from randomization to death from any cause.
- Very Good Partial Response (VGPR) Rate [ Time Frame: Assessed every cycle (1 cycle=28 days) for the first 12 cycles, and then every 2 cycles while on treatment. Post treatment assessed every 3 months < 2 years from study entry, every 6 months if 2-5 years, every 12 months if 6-10 years from study entry. ]Response evaluation was based on the International Myeloma Working Group (IMWG) response criteria. VGPR rate was defined as patients achieving at least VGPR which include patients who achieving complete response (CR) and VGPR. CR refers to patients who have complete disappearance of an M-protein and no evidence of myeloma in the bone marrow. VGPR refers to patients who meet the following criteria: Serum and urine M-component detectable by immunofixation but not on electrophoresis; Or 90% or greater reduction in serum M-component plus urine M-component <100 mg per 24 hours; If the serum and urine M protein are unmeasurable and the immunoglobulin free light chain parameter is being used to measure response, a ≥ 90% decrease in the difference between involved and uninvolved free light chain (FLC) levels is required in place of the M protein criteria.
- Change in Functional Assessment of Cancer Therapy-Neurotoxicity Trial Outcome Index (FACT-Ntx TOI) Score From Baseline to Cycle 12 [ Time Frame: Administered at registration, the beginning of cycle 7 d1, the end of cycle 12 d28, then at the end of cycle 18, 24, and 38 d28. For patients who discontinue treatment early, assessed at time of discontinuation and at the next quarterly follow-up visit. ]A combined scale was used to assess the quality of life (QOL) comprising of the well established and validated functional well-being (FWB) and physical well-being (PWB) components of FACT-G version 4 (14 questions), which will address the physical and functional well-being of multiple myeloma patients plus the FACT-neurotoxicity (NTX, 11 questions), which will evaluate symptoms of neurotoxicity. This pooled scale is referred to as the FACT Ntx TOI. The FACT-Ntx TOI has 25 items and the score ranges from 0 (worst possible outcome) to 100 (best possible outcome).
|Study Start Date:||February 2008|
|Estimated Study Completion Date:||November 2021|
|Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
Active Comparator: Arm I (MPT-T)
Patients receive melphalan, prednisone and thalidomide induction plus thalidomide maintenance (MPT-T).
INDUCTION THERAPY: Patients receive melphalan 9mg/m^2 PO and prednisone 100 mg PO QD on days 1-4, and thalidomide 100 mg PO QD on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Patients receive thalidomide 100 mg PO QD and continue in the absence of disease progression.
Other Names:Drug: prednisone
Other Names:Drug: thalidomide
Experimental: Arm II (mPR-R)
Patients receive lower-dose melphalan, prednisone and lenalidomide (Revlimid®) induction plus lenalidomide maintenance (mPR-R).
INDUCTION THERAPY: Patients receive melphalan 5mg/m^2 PO and prednisone 100 mg PO QD on days 1-4, and lenalidomide 10 mg PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Patients receive lenalidomide 10 mg PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression.
Other Names:Drug: prednisone
Other Names:Drug: lenalidomide
I. To compare progression-free survival between patients receiving melphalan, prednisone, and thalidomide versus melphalan, prednisone, and lenalidomide in newly diagnosed multiple myeloma patients who are not candidates for high-dose therapy.
I. To compare overall survival between the arms.
II. To compare response rates and depth of response.
III. To compare the incidence of toxicities. IV. To validate the translocation (TC) classification of myeloma as a prognostic tool using gene expression profiling at diagnosis.
I. To compare quality-of-life (QOL) change between arms based on the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT-Ntx) Trial Outcome Index (TOI) from baseline to the end of course 24 (maintenance therapy).
II. To examine the impact of differential treatment responses, if observed, on QOL based on the FACT-Ntx TOI up to cycle 38 (maintenance therapy).
III. To obtain prospective data on myeloma specific QOL attributes.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
INDUCTION THERAPY: Patients receive melphalan orally (PO) and prednisone PO once daily (QD) on days 1-4, and thalidomide PO QD on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Patients receive thalidomide PO QD and continue in the absence of disease progression.
INDUCTION THERAPY: Patients receive melphalan PO and prednisone PO QD on days 1-4, and lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Patients receive lenalidomide PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression.
After completion of study treatment, patients will be followed periodically for 10 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00602641
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|Principal Investigator:||Alexander Stewart||Mayo Clinic|