A Phase III, Randomized, Open-Label, 3-Arm Study To Determine the Efficacy and Safety of Lenalidomide (Revlimid) Plus Low-Dose Dexamethasone When Given Until Progressive Disease or for 18 Four-Week Cycles Versus the Combination of Melphalan, Prednisone, and Thalidomide Given for 12 Six-Week Cycles in Patients with Previously Untreated Multiple Myeloma Who Are Either 65 Years of Age or Older or Not Candidates for Stem Cell Transplantation (IFM 07-01) - FIRST

Phase 1

• Conditions: Multiple Myeloma; MedDRA version: 9.1Level: LLTClassification code 10028228Term: Multiple myeloma

• Registration Number: EUCTR2007-004823-39-IT
• Lead Sponsor: Celgene Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-05-20
• Last Update Posted: 29 August 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1590

Inclusion Criteria

1.Must understand and voluntarily sign informed consent form
2.Age ≥ 18 years at the time of signing consent
3.Previously untreated, symptomatic multiple myeloma as defined by the 3 criteria below:
MM diagnostic criteria (all 3 required):
Monoclonal plasma cells in the bone marrow ≥10% and/or presence of a biopsy-proven plasmacytoma
Monoclonal protein present in the serum and/or urine
Myeloma-related organ dysfunction (at least one of the following)
[C] Calcium elevation in the blood (serum calcium >10.5 mg/l or upper limit of normal)
[R] Renal insufficiency (serum creatinine >2 mg/dL)
[A] Anemia (hemoglobin <10 g/dL or 2 g < normal)
[B] Lytic bone lesions or osteoporosis
AND have measurable disease by protein electrophoresis analyses as defined by the following:
IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level  1.0 g/dL or urine M-protein level  200 mg/24 hours
IgA multiple myeloma: Serum M-protein level  0.5 g/dL or urine M-protein level  200 mg/24 hours
IgM multiple myeloma (IgM M-protein plus lytic bone disease documented by skeletal survey plain films): Serum M-protein level ≥ 1.0 g/dL or urine M-protein level ≥ 200mg/24hours
IgD multiple myeloma: Serum M-protein level  0.05 g/dL or urine M-protein level  200 mg/24 hours
Light chain multiple myeloma: Serum M-protein level  1.0 g/dL or urine M-protein level  200 mg/24 hours
AND are at least 65 years of age or older or, if younger than 65 years of age, are not candidates for stem cell transplantation because:
The patient declines to undergo stem cell transplantation
or
Stem cell transplantation is not available to the patient due to cost or other reasons
4.ECOG performance status of 0, 1, or 2 (see Appendix 21.4)
5.Able to adhere to the study visit schedule and other protocol requirements
6.Females of child-bearing potential (FCBP)2:
a. Must agree to undergo two medically supervised pregnancy tests prior to starting study therapy with either Rd or MPT. The first pregnancy test will be performed within 10-14 days prior to the start of Rd or MPT and the second pregnancy test will be performed within 24 hours prior to the start of Rd or MPT. She must also agree to ongoing pregnancy testing during the course of the study and after the end of study therapy (see Appendix 21.6). This applies even if the patient practices complete and continued sexual abstinence.
b.Must commit to either continued abstinence from heterosexual intercourse (which must be reviewed on a monthly basis) or agree to use and be able to comply with effective contraception without interruption, 28 days prior to starting study drug, during the study therapy (including during periods of dose interruptions), and for 28 days after discontinuation of study therapy (see Appendix 21.6).
7.Male Patients:
a.Must agree to use a condom during sexual contact with a FCBP, even if they have had a vasectomy, throughout study drug therapy, during any dose interruption and after cessation of study therapy (see Appendix 21.6).
b.Must agree to not donate semen during study drug therapy and for a period after end of study drug therapy (see Appendix 21.6).
8.All patients must:
a.Have an understanding that the study drug could have a potential teratogenic risk.
b.Agree to abstain from donating blood while taking study drug therapy and following discontinuation of study drug therapy (see Appendix 21.6).
c

Exclusion Criteria

1.Previous treatment with antimyeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid [i.e., less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days; such a short course of steroid treatment must not have been given within 28 days (4 weeks) of randomization]).
2.Any serious medical condition that places the patient at an unacceptable risk if he or she participates in this study.
3.Pregnant or lactating females.
4.Any of the following laboratory abnormalities:
Absolute neutrophil count (ANC) < 1,000/L (1.0 x 109/L)
Untransfused platelet count < 50,000 cells/L (50 x 109/L)
Serum SGOT/AST or SGPT/ALT > 3.0 x upper limit of normal (ULN)
5.Renal failure requiring hemodialysis or peritoneal dialysis.
6.Prior history of malignancies, other than multiple myeloma, unless the patient has been free of the disease for  3 years. Exceptions include the following:
Basal cell carcinoma of the skin
Squamous cell carcinoma of the skin
Carcinoma in situ of the cervix
Carcinoma in situ of the breast
Incidental histological finding of prostate cancer (TNM stage of T1a or T1b)
7.Patients who are unable or unwilling to undergo antithrombotic therapy.
8.Peripheral neuropathy of > grade 2 severity.
9.Known HIV positivity or active infectious hepatitis, type A, B, or C.
10.Primary AL (immunoglobulin light chain) amyloidosis and myeloma complicated by amyloidosis

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the efficacy of lenalidomide plus low-dose dexamethasone given until progressive disease to that of the combination of melphalan, prednisone, and thalidomide given for 12 six-week cycles.;Secondary Objective: To compare the efficacy of lenalidomide plus low-dose dexamethasone given for 18 four-week cycles to that of the combination of melphalan, prednisone, and thalidomide given for 12 six-week cycles. <br> To assess the safety of lenalidomide plus low-dose dexamethasone versus that of the combination of melphalan, prednisone, and thalidomide. <br> To assess the safety and efficacy of lenalidomide plus low-dose dexamethasone therapy given until progressive disease versus the safety and efficacy of lenalidomide plus low-dose dexamethasone given for 18 four-week cycles.;Primary end point(s): Progression-free survival (PFS)