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: September 15, 2014
Last verified: May 2014

January 18, 2008
September 15, 2014
February 2008
January 2014   (final data collection date for primary outcome measure)
  • Progression-free survival [ Time Frame: From randomization to the earlier of progression or death of any cause, assessed up to 10 years ] [ Designated as safety issue: No ]
    Tested using one-sided 0.95 confidence limits.
  • Mean change of the FACT-Ntx TOI score and the multiple myeloma specific subscale instruments (MMS) [ Time Frame: Baseline to up to week 96 ] [ Designated as safety issue: No ]
    Differences between treatment arms are detected by 2-sample t-test, with 80% power, at a two-sided 0.05 significance level. Analyzed according to the methods described in Schluchter and in Schluchter, Greene and Beck.
  • 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
  • Response rates (complete response + very good partial response + partial response) based on International Uniform Response Criteria for Multiple Myeloma [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Compared between arms using the Fisher's exact test.
  • Overall survival [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Estimated using the method of Kaplan and Meier. Compared between the two arms using two-sided stratified log-rank test.
  • Toxicity (rates of grade 3 or higher serious adverse events on the two arms), graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
    Compared using the Fisher's exact test.
  • Change in the FACT-Ntx TOI mean scores between patients that experience disease progression (PD) [ Time Frame: Baseline up to week 152 ] [ Designated as safety issue: No ]
    Evaluated using mixed effects model.
  • Change in the FACT-Ntx TOI mean scores between patients that do not experience PD [ Time Frame: Baseline up to week 152 ] [ Designated as safety issue: No ]
    Evaluated using mixed effects model. Analyzed according to the methods described in Schluchter and in Schluchter, Greene and Beck.
  • 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 ]
  • Reliability between the MMS subscales [ Time Frame: Up to week 96 ] [ Designated as safety issue: No ]
    Provided with descriptive statistics and calculated using Chronbach's alpha.
  • Reliability between the Ntx subscales [ Time Frame: Up to week 96 ] [ Designated as safety issue: No ]
    Provided with descriptive statistics and calculated using Chronbach's alpha.
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
  • Other: quality-of-life assessment
    Ancillary studies
    Other Name: quality of life assessment
  • Other: laboratory biomarker analysis
    Optional correlative studies
  • Active Comparator: Arm I (thalidomide)

    INDUCTION THERAPY: Patients receive melphalan PO and prednisone PO 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.

    Interventions:
    • Drug: melphalan
    • Drug: prednisone
    • Drug: thalidomide
    • Other: quality-of-life assessment
    • Other: laboratory biomarker analysis
  • Experimental: Arm II (lenalidomide)

    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.

    Interventions:
    • Drug: melphalan
    • Drug: prednisone
    • Drug: lenalidomide
    • Other: laboratory biomarker analysis
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
307
Not Provided
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
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days and again within 24 hours prior to starting cycle 1 of lenalidomide; further, they 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 starting 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; a FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months); all patients must be counseled by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure
  • Patients must not have 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
  • Patients must not have grade 2 or higher peripheral neuropathy
  • Patients must not have an active, uncontrolled infection
  • Female patients MUST NOT be 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
  • Patients must not have had a 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, NCI-2009-00522, CDR0000583984, ECOG-E1A06, E1A06, E1A06, U10CA180820, U10CA021115
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Alexander Stewart ECOG-ACRIN Cancer Research Group
National Cancer Institute (NCI)
May 2014

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