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
  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) 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: 460
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
Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid
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
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
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Hide Study Locations
Locations
United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
University of California at Davis Cancer Center
Sacramento, California, United States, 95817
University of California At San Diego
San Diego, California, United States, 92103
UCSF-Mount Zion
San Francisco, California, United States, 94115
United States, Colorado
The Medical Center of Aurora
Aurora, Colorado, United States, 80012
Boulder Community Hospital
Boulder, Colorado, United States, 80301
Penrose-Saint Francis Healthcare
Colorado Springs, Colorado, United States, 80907
Exempla Saint Joseph Hospital
Denver, Colorado, United States, 80218
Colorado Cancer Research Program CCOP
Denver, Colorado, United States, 80224-2522
Porter Adventist Hospital
Denver, Colorado, United States, 80210
Rose Medical Center
Denver, Colorado, United States, 80220
Presbyterian - Saint Lukes Medical Center - Health One
Denver, Colorado, United States, 80218
Swedish Medical Center
Englewood, Colorado, United States, 80113
Saint Mary's Hospital and Regional Medical Center
Grand Junction, Colorado, United States, 81502
North Colorado Medical Center
Greeley, Colorado, United States, 80631
Saint Anthony Hospital
Lakewood, Colorado, United States, 80228
Sky Ridge Medical Center
Lone Tree, Colorado, United States, 80124
Longmont United Hospital
Longmont, Colorado, United States, 80501
McKee Medical Center
Loveland, Colorado, United States, 80539
Saint Mary Corwin Medical Center
Pueblo, Colorado, United States, 81004
North Suburban Medical Center
Thornton, Colorado, United States, 80229
Exempla Lutheran Medical Center
Wheat Ridge, Colorado, United States, 80033
United States, Delaware
Saint Francis Hospital - Wilmington
Wilmington, Delaware, United States, 19805
United States, District of Columbia
George Washington University Medical Center
Washington, District of Columbia, United States, 20037
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224-9980
United States, Georgia
Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, United States, 30342
Georgia Regents University
Augusta, Georgia, United States, 30912
United States, Illinois
Saint Joseph Medical Center
Bloomington, Illinois, United States, 61701
Graham Hospital Association
Canton, Illinois, United States, 61520
Memorial Hospital
Carthage, Illinois, United States, 62321
University of Illinois
Chicago, Illinois, United States, 60612
Cancer and Leukemia Group B
Chicago, Illinois, United States, 60606
Jesse Brown Veterans Affairs Medical Center
Chicago, Illinois, United States, 60612
University of Chicago
Chicago, Illinois, United States, 60637
Eureka Hospital
Eureka, Illinois, United States, 61530
Illinois CancerCare Galesburg
Galesburg, Illinois, United States, 61401
Galesburg Cottage Hospital
Galesburg, Illinois, United States, 61401
Mason District Hospital
Havana, Illinois, United States, 62644
Hopedale Medical Complex - Hospital
Hopedale, Illinois, United States, 61747
Kewanee Hospital
Kewanee, Illinois, United States, 61443
Mcdonough District Hospital
Macomb, Illinois, United States, 61455
Bromenn Regional Medical Center
Normal, Illinois, United States, 61761
Community Cancer Center Foundation
Normal, Illinois, United States, 61761
Illinois CancerCare-Ottawa Clinic
Ottawa, Illinois, United States, 61350
Ottawa Regional Hospital and Healthcare Center
Ottawa, Illinois, United States, 61350
Pekin Cancer Treatment Center
Pekin, Illinois, United States, 61554
Pekin Hospital
Pekin, Illinois, United States, 61554
OSF Saint Francis Medical Center
Peoria, Illinois, United States, 61637
Illinois Oncology Research Association CCOP
Peoria, Illinois, United States, 61615
Proctor Hospital
Peoria, Illinois, United States, 61614
Methodist Medical Center of Illinois
Peoria, Illinois, United States, 61603
Illinois CancerCare-Peoria
Peoria, Illinois, United States, 61615
Illinois Valley Hospital
Peru, Illinois, United States, 61354
Perry Memorial Hospital
Princeton, Illinois, United States, 61356
Saint Margaret's Hospital
Spring Valley, Illinois, United States, 61362
United States, Indiana
Indiana University Medical Center
Indianapolis, Indiana, United States, 46202
United States, Kansas
Providence Medical Center
Kansas City, Kansas, United States, 66112
Lawrence Memorial Hospital
Lawrence, Kansas, United States, 66044
Radiation Oncology Practice Corporation Southwest
Overland Park, Kansas, United States, 66210
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Minnesota
University of Minnesota Medical Center-Fairview
Minneapolis, Minnesota, United States, 55455
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
United States, Missouri
Centerpoint Medical Center LLC
Independence, Missouri, United States, 64057
Radiation Oncology Practice Corporation South
Kansas City, Missouri, United States, 64114
Radiation Oncology Practice Corporation - North
Kansas City, Missouri, United States, 64154
Saint Luke's Cancer Institute
Kansas City, Missouri, United States, 64111
Liberty Hospital
Liberty, Missouri, United States, 64068
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, New Jersey
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08903
United States, New York
Albert Einstein College of Medicine
Bronx, New York, United States, 10461
Montefiore Medical Center
Bronx, New York, United States, 10467-2490
Montefiore Medical Center-Wakefield Campus
Bronx, New York, United States, 10466
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
North Shore University Hospital
Manhasset, New York, United States, 11030
North Shore-LIJ Health System CCOP
Manhasset, New York, United States, 11030
Long Island Jewish Medical Center
New Hyde Park, New York, United States, 11040
Mount Sinai Medical Center
New York, New York, United States, 10029
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Weill Medical College of Cornell University
New York, New York, United States, 10065
University of Rochester
Rochester, New York, United States, 14642
State University of New York Upstate Medical University
Syracuse, New York, United States, 13210
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
Carolinas Medical Center
Charlotte, North Carolina, United States, 28203
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
The Jewish Hospital
Cincinnati, Ohio, United States, 45236
Case Western Reserve University
Cleveland, Ohio, United States, 44106
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Geisinger Medical Center
Danville, Pennsylvania, United States, 17822-2001
Geisinger Medical Center-Cancer Center Hazleton
Hazleton, Pennsylvania, United States, 18201
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, United States, 19104
Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, United States, 15224-1791
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15232
Geisinger Medical Group
State College, Pennsylvania, United States, 16801
Geisinger Wyoming Valley
Wilkes-Barre, Pennsylvania, United States, 18711
United States, South Carolina
Greenville Memorial Hospital
Greenville, South Carolina, United States, 29605
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Utah
LDS Hospital
Salt Lake City, Utah, United States, 84143
United States, Vermont
Central Vermont Medical Center/National Life Cancer Treatment
Berlin, Vermont, United States, 05602
University of Vermont
Burlington, Vermont, United States, 05401
United States, Washington
University of Washington Medical Center
Seattle, Washington, United States, 98195
United States, West Virginia
Saint Mary's Medical Center
Huntington, West Virginia, United States, 25702
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Marshfield Clinic
Marshfield, Wisconsin, United States, 54449
Froedtert and the Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Marshfield Clinic at James Beck Cancer Center
Rhinelander, Wisconsin, United States, 54501
Marshfield Clinic-Rice Lake Center
Rice Lake, Wisconsin, United States, 54868
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, P30CA014236
Study First Received: June 13, 2005
Results First Received: March 28, 2013
Last Updated: June 18, 2014
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 August 18, 2014