Overview

This trial is active, not recruiting.

Conditions stage i multiple myeloma, stage ii multiple myeloma, stage iii multiple myeloma
Treatments melphalan, prednisone, thalidomide, lenalidomide
Phase phase 3
Sponsor National Cancer Institute (NCI)
Start date February 2008
End date January 2014
Trial size 306 participants
Trial identifier NCT00602641, E1A06, NCI-2009-00522, U10CA021115

Summary

This randomized phase III trial studies melphalan and prednisone with thalidomide to see how well it works compared to melphalan and prednisone together with lenalidomide in treating patients with newly diagnosed multiple myeloma. Drugs used in chemotherapy, such as melphalan and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Thalidomide and lenalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. It is not yet known whether melphalan and prednisone are more effective when given together with thalidomide or lenalidomide in treating multiple myeloma.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
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.
melphalan Alkeran
Given PO
prednisone DeCortin
Given PO
thalidomide Kevadon
Given PO
(Experimental)
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.
melphalan Alkeran
Given PO
prednisone DeCortin
Given PO
lenalidomide CC-5013
Given PO

Primary Outcomes

Measure
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.

Secondary Outcomes

Measure
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.
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.
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.

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Patients must have a confirmed diagnosis of symptomatic myeloma; for the original diagnosis of myeloma patients should have met the following criteria at one point in their disease course: - Bone marrow plasmacytosis with >= 10% plasma cells or sheets of plasma cells or biopsy proven plasmacytoma - Patient must have had symptomatic disease at initial diagnosis that prompted the initiation of therapy as well as evidence of end-organ damage at the time of diagnosis namely; at least one of the following: anemia, hypercalcemia, bone disease (lytic bone lesions or pathologic fracture), or renal dysfunction - NOTE: Patients with asymptomatic smoldering myeloma (serum m protein >= 3 gm/dL or bone marrow plasma cells >= 10% or greater plus no evidence of anemia, hypercalcemia, lytic bone lesions or renal dysfunction) and monoclonal gammopathy of undetermined significance (serum m protein < 3 gm/dL and bone marrow plasma cells < 10% plus no evidence of anemia, hypercalcemia, lytic bone lesions or renal dysfunction) are not eligible - Patients must be > 65 and have declined alternative treatment OR patients who are >= 18 < 65 are eligible if they: - Are not a candidate for autologous stem cell transplantation in the opinion of the treating physician OR - Have declined transplant or other alternative treatment - Eastern Cooperative Oncology Group (ECOG) performance status =< 2 - All tests below must be performed within 28 days prior to randomization: - Serum free light chain assay - Kappa free light chain - Lambda free light chain - NOTE: The serum free light chain test is required to be done if the patient does not have measurable disease in the serum or urine; measurable disease in the serum is defined as having a serum M-spike >= 1 g/dL; measurable disease in the urine is defined as having a urine M-spike >= 200 mg/24 hr - NOTE: urine protein electrophoresis (UPEP) (on a 24 hour collection) is required, no substitute method is acceptable; urine must be followed monthly if the baseline urine M-spike is >= 200 mg/24 hr; please note that if both serum and urine m-components are present, both must be followed in order to evaluate response - Hemoglobin > 7 g/dL - Platelet count > 75,000 cells/mm^3 - Absolute neutrophil count > 1000 cells/mm^3 - Creatinine < 2.5 mg/dL and creatinine clearance (measured or calculated) > 60 mL/min - Total bilirubin =< 1.5 mg/dL - Serum glutamate pyruvate transaminase (SGPT) [alanine aminotransferase (ALT)] and serum glutamic oxaloacetic transaminase (SGOT) [aspartate aminotransferase (AST)] =< 2.5 times the upper limit of normal - Patients must be previously untreated for myeloma, although prior treatment for myeloma with prednisone or dexamethasone for less than 4 weeks total dosing alone or in combination with thalidomide or lenalidomide for less than 2 weeks total dosing is allowable - Patients may be receiving bisphosphonates or growth factors (erythropoietin) for multiple myeloma; although erythropoietin is allowed, it is strongly discouraged due to increased risk of thrombosis when employed alongside thalidomide and/or lenalidomide therapy - Patients must be willing and able to take prophylaxis with either aspirin at 325 mg/day or alternative prophylaxis with either low molecular weight heparin or coumadin Exclusion Criteria: - Pregnant or breastfeeding. The use of these drugs in this patient population is ABSOLUTELY CONTRAINDICATED; for women of childbearing potential, a negative serum pregnancy test is required within 10-14 days prior to randomization; for female patients of childbearing potential a negative serum pregnancy test must be repeated within 24 hours prior to initiation of treatment, weekly for the first 4 weeks of treatment and then every 4 weeks if the patient's periods are regular or every 2 weeks if they are not; women of childbearing potential must be willing to refrain from sexual intercourse or must be willing to employ a dual method of contraception, one of which is highly effective (intrauterine device (IUD), birth control pills, tubal ligation or partner's vasectomy) and another additional method (condom, diaphragm or cervical cap) starting 4 weeks prior to and while taking lenalidomide and thalidomide and for four weeks after discontinuing this therapy; the male partner of a female using a single form of birth control should use a condom regardless of his vasectomy status. Sexually active males must be willing to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking lenalidomide and thalidomide and for 4 weeks after stopping treatment. - Uncontrolled inter-current illness that would limit compliance with the study including: - Uncontrolled hypertension - Symptomatic congestive heart failure - Unstable angina - Uncontrolled cardiac arrhythmia - Uncontrolled psychiatric illness or social situation - Prior history of Stevens Johnson syndrome - Grade 2 or higher peripheral neuropathy - Active, uncontrolled infection - Second active malignancy requiring treatment within the last 2 years, with the exceptions of basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix

Additional Information

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
Principal investigator Alexander Stewart
Description PRIMARY OBJECTIVES: 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. SECONDARY OBJECTIVES: 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. TERTIARY OBJECTIVES: 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. ARM I: 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. ARM II: 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.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).