Melphalan, Prednisone, and Thalidomide or Lenalidomide in Treating Patients With Newly Diagnosed Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00602641
First received: January 18, 2008
Last updated: June 9, 2015
Last verified: March 2015

January 18, 2008
June 9, 2015
February 2008
January 2014   (final data collection date for primary outcome 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. ] [ Designated as safety issue: No ]
PFS is defined as the time from randomization to the earlier of progression or death of any cause.
  • Progression-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00602641 on ClinicalTrials.gov Archive Site
  • 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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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).
  • Response rates and depth of response comparison [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]
  • Quality-of-life (QOL) change comparison of arms measured by FACT-Ntx TOI from baseline to course 24 [ Designated as safety issue: No ]
  • Differential treatment response on QOL measured by FACT-Ntx TOI from baseline to course 38 [ Designated as safety issue: No ]
  • TC classification validation of myeloma as a prognostic tool using gene expression profiling [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Melphalan, Prednisone, and Thalidomide or Lenalidomide in Treating Patients With Newly Diagnosed Multiple Myeloma
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

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Stage I Multiple Myeloma
  • Stage II Multiple Myeloma
  • Stage III Multiple Myeloma
  • Drug: melphalan
    Given PO
    Other Names:
    • Alkeran
    • CB-3025
    • L-PAM
    • L-phenylalanine mustard
    • L-Sarcolysin
  • Drug: prednisone
    Given PO
    Other Names:
    • DeCortin
    • Deltra
  • Drug: thalidomide
    Given PO
    Other Names:
    • Kevadon
    • Synovir
    • THAL
    • Thalomid
  • Drug: lenalidomide
    Given PO
    Other Names:
    • CC-5013
    • IMiD-1
    • Revlimid
  • 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.

    Interventions:
    • Drug: melphalan
    • Drug: prednisone
    • 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.

    Interventions:
    • Drug: melphalan
    • Drug: prednisone
    • Drug: lenalidomide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
306
November 2021
January 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Israel
 
NCT00602641
NCI-2009-00522, E1A06, U10CA021115
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Alexander Stewart Mayo Clinic
National Cancer Institute (NCI)
March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP