Lenalidomide in Treating Patients Who Are Undergoing Autologous Stem Cell Transplant for Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00114101
First received: June 13, 2005
Last updated: June 18, 2014
Last verified: June 2014

June 13, 2005
June 18, 2014
December 2004
December 2012   (final data collection date for primary outcome measure)
Time to Progression [ Time Frame: Duration of study (up to 10years) ] [ Designated as safety issue: No ]

Time to progression (TTP) was defined as the date of transplant to date of progression or death due to any cause, whichever occurs first. TTP was estimated using the Kaplan Meier method.

Progression was defined per the International Myeloma Working Group definition as one more of the following:

  • 25% increase in serum M-component (absolute increase >= 0.5g/dl)
  • 25% increase in urine M-component (absolute increase >= 200mg/24hour
  • 25% increase in the difference between involved and uninvolved Free Light Chain levels (absolute increase >= 10mg/dl)
  • 25 % increase in bone marrow plasma cell percentage (absolute increase of >=10%)
  • Definite development of new bone lesion or soft tissue plasmacytomas
  • Development of hypercalcemia
Not Provided
Complete list of historical versions of study NCT00114101 on ClinicalTrials.gov Archive Site
Response to Autologous Hematopoietic Stem-cell Transplant (HSCT) at Day 100 [ Time Frame: Day 100 ] [ Designated as safety issue: No ]

Response was defined according to International Myeloma Working Group criteria (2006)

  • Complete Response: Complete disappearance of M-protein from serum & urine on immunofixation, normalization of Free Light Chain (FLC) ratio & <5% plasma cells in bone marrow (BM)
  • Partial Response: >= 50% reduction in serum M-Component and/or Urine M-Component >= 90% reduction or <200 mg per 24 hours; or >= 50% decrease in difference between involved and uninvolved FLC levels
  • Marginal Response: 25-49% reduction in serum M-component & urine M-component by 50-89% which still exceeds 200mg/24hour
  • Progressive Disease: Defined in primary outcome measure
  • Stable Disease: Not meeting any of the criteria above
Not Provided
Overall Survival [ Time Frame: Duration of study (up to 10 years) ] [ Designated as safety issue: Yes ]
Overall Survival was measured from the date of randomization to date of death due to any cause. OS was estimated using the Kaplan Meier method.
Not Provided
 
Lenalidomide in Treating Patients Who Are Undergoing Autologous Stem Cell Transplant for Multiple Myeloma
A Phase III Randomized, Double-Blind Study of Maintenance Therapy With CC-5013 (NSC # 703813) or Placebo Following Autologous Stem Cell Transplantation for Multiple Myeloma

This randomized phase III trial is studying lenalidomide to see how well it works compared to a placebo in treating patients who are undergoing autologous stem cell transplant for multiple myeloma. A peripheral stem cell transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Giving lenalidomide after autologous stem cell transplant may stop or slow the return of cancer. It is not yet known whether lenalidomide is more effective than a placebo when given after autologous stem cell transplant in treating multiple myeloma.

PRIMARY OBJECTIVES:

I. Compare the efficacy of lenalidomide vs placebo as maintenance therapy after autologous stem cell transplantation, in terms of prolonging time to disease progression, in patients with multiple myeloma.

SECONDARY OBJECTIVES:

I. Compare the rate of complete response in patients treated with these regimens.

II. Compare the progression-free and overall survival of patients treated with these regimens.

III. Determine the feasibility of long-term treatment with lenalidomide in these patients

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study.

PERIPHERAL BLOOD STEM CELL (PBSC) MOBILIZATION: Patients receive high-dose cyclophosphamide IV over 2-3 hours on day 1 OR IV over 1 hour every 3 hours three times on day 1. Patients also receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 5 and continuing until PBSC collection is complete. Patients then undergo leukapheresis for collection of PBSC.

AUTOLOGOUS PBSC TRANSPLANTATION (PBSCT): Approximately 2-4 weeks after PBSC collection, patients receive melphalan IV over 30-60 minutes on day -2. Patients undergo autologous PBSCT on day 0. Patients receive G-CSF SC once daily beginning on day 5 and continuing until blood counts recover.

MAINTENANCE THERAPY*: Approximately 90-100 days after completion of autologous PBSCT, patients undergo restaging. Patients with disease progression are removed from the study. Patients with responding or stable disease are stratified according to levels of beta2 microglobulin at baseline ( >= 2.5 mg/dL vs normal), prior thalidomide (yes vs no), and prior lenalidomide (yes vs no). Patients are randomized to 1 of 2 maintenance treatment arms.

ARM I: Beginning between day 100-110, patients receive oral lenalidomide once daily.

ARM II: Beginning between day 100-110, patients receive oral placebo once daily.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

[Note: *The maintenance dose is increased to a maximum dose of 3 pills over 3-6 months]

After completion of study treatment, patients are followed every 3 months for 4 years and every 6 months thereafter.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • Refractory Multiple Myeloma
  • Stage I Multiple Myeloma
  • Stage II Multiple Myeloma
  • Stage III Multiple Myeloma
  • Drug: lenalidomide
    Given orally
    Other Names:
    • CC-5013
    • IMiD-1
    • Revlimid
  • Other: placebo
    Given orally
    Other Name: PLCB
  • Procedure: peripheral blood stem cell transplantation
    Undergo transplantation
    Other Names:
    • PBPC transplantation
    • PBSC transplantation
    • peripheral blood progenitor cell transplantation
    • transplantation, peripheral blood stem cell
  • Drug: melphalan
    Given IV
    Other Names:
    • Alkeran
    • CB-3025
    • L-PAM
    • L-phenylalanine mustard
    • L-Sarcolysin
  • Drug: cyclophosphamide
    Given IV
    Other Names:
    • CPM
    • CTX
    • Cytoxan
    • Endoxan
    • Endoxana
  • Biological: filgrastim
    Given subcutaneously
    Other Names:
    • G-CSF
    • Neupogen
  • Experimental: Maintenance therapy arm I
    Beginning between day 100-110, patients receive oral lenalidomide once daily.
    Interventions:
    • Drug: lenalidomide
    • Procedure: peripheral blood stem cell transplantation
    • Drug: melphalan
    • Drug: cyclophosphamide
    • Biological: filgrastim
  • Placebo Comparator: Maintenance therapy arm II
    Beginning between day 100-110, patients receive oral placebo once daily.
    Interventions:
    • Other: placebo
    • Procedure: peripheral blood stem cell transplantation
    • Drug: melphalan
    • Drug: cyclophosphamide
    • Biological: filgrastim
McCarthy PL, Owzar K, Hofmeister CC, Hurd DD, Hassoun H, Richardson PG, Giralt S, Stadtmauer EA, Weisdorf DJ, Vij R, Moreb JS, Callander NS, Van Besien K, Gentile T, Isola L, Maziarz RT, Gabriel DA, Bashey A, Landau H, Martin T, Qazilbash MH, Levitan D, McClune B, Schlossman R, Hars V, Postiglione J, Jiang C, Bennett E, Barry S, Bressler L, Kelly M, Seiler M, Rosenbaum C, Hari P, Pasquini MC, Horowitz MM, Shea TC, Devine SM, Anderson KC, Linker C. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med. 2012 May 10;366(19):1770-81. doi: 10.1056/NEJMoa1114083.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
460
Not Provided
December 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosis of multiple myeloma:

    • Active disease requiring treatment;
    • Durie-Salmon Stage I, II, or III
  • Stable disease or responsive after >= 2 months of induction therapy initiated within the past year
  • No prior disease progression after initial therapy
  • Patients with smoldering myeloma are eligible provided disease has progressed to >= stage I
  • Performance status:

    • ECOG 0-1
  • Hematopoietic:

    • Absolute neutrophil count >= 1,000/mm^3;
    • Platelet count >= 100,000/mm^3
  • Hepatic:

    • Hepatitis B surface antigen negative;
    • Hepatitis C negative;
    • Bilirubin =< 2 mg/dL;
    • AST =< 3 times upper limit of normal (ULN);
    • Alkaline phosphatase =< 3 times ULN
  • Renal:

    • Creatinine clearance >= 40 mL/min;
    • Creatinine =< 2 mg/dL
  • Cardiovascular:

    • LVEF >= 40% by MUGA or echocardiogram
  • Pulmonary:

    • DLCO > 50% of predicted;
    • No symptomatic pulmonary disease
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective double-method contraception
  • HIV negative
  • No uncontrolled diabetes mellitus
  • No serious active infection
  • Prior thalidomide or lenalidomide allowed provided treatment duration was =< 12 months
  • No prior bone marrow or peripheral blood stem cell transplantation
  • No concurrent pegfilgrastim
  • No prior solid organ transplantation
  • Prior therapy allowed provided treatment duration was =< 12 months
  • Peripheral blood stem cell collection of >= 2 x 10^6 CD34+ cells/kg (patient body weight) and preferably 5 x 10^6 cells/kg (patient body weight);

    • Stem cells may be collected at any time prior to transplant
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00114101
NCI-2009-00439, NCI-2009-00439, CDR0000434845, CALGB 100104/ECOG 100104, CALGB-100104, U10CA031946, P30CA014236
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Philip McCarthy Cancer and Leukemia Group B
National Cancer Institute (NCI)
June 2014

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