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: September 4, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Refractory Multiple Myeloma
Stage I Multiple Myeloma
Stage II Multiple Myeloma
Stage III Multiple Myeloma
Drug: lenalidomide
Other: placebo
Procedure: peripheral blood stem cell transplantation
Drug: melphalan
Drug: cyclophosphamide
Biological: filgrastim
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III Randomized, Double-Blind Study of Maintenance Therapy With CC-5013 (NSC # 703813, IND # 70116) or Placebo Following Autologous Stem Cell Transplantation for Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Other Outcome Measures:
  • 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.


Enrollment: 462
Study Start Date: December 2004
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Maintenance therapy arm I
Beginning between day 100-110, patients receive oral lenalidomide once daily.
Drug: lenalidomide
Given orally
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
Biological: filgrastim
Given subcutaneously
Other Names:
  • G-CSF
  • Neupogen
Placebo Comparator: Maintenance therapy arm II
Beginning between day 100-110, patients receive oral placebo once daily.
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
Biological: filgrastim
Given subcutaneously
Other Names:
  • G-CSF
  • Neupogen

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00114101

  Show 114 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Philip McCarthy Cancer and Leukemia Group B
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00114101     History of Changes
Other Study ID Numbers: NCI-2009-00439, NCI-2009-00439, CDR0000434845, CALGB 100104/ECOG 100104, CALGB-100104, U10CA031946
Study First Received: June 13, 2005
Results First Received: March 28, 2013
Last Updated: September 4, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Melphalan
Lenalidomide
Lenograstim
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on April 22, 2014