Lenalidomide in Treating Patients 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: July 29, 2015
Last verified: May 2015
  Purpose

This randomized phase III trial studies lenalidomide to see how well it works compared to a placebo in treating patients who are undergoing autologous stem cell transplant for multiple myeloma. Giving chemotherapy before a peripheral blood stem cell transplant helps kill any cancer cells that are in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Biological therapies, such as lenalidomide, may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Giving lenalidomide after autologous stem cell transplant may be an effective treatment for multiple myeloma.


Condition Intervention Phase
DS Stage I Plasma Cell Myeloma
DS Stage II Plasma Cell Myeloma
DS Stage III Plasma Cell Myeloma
Refractory Plasma Cell Myeloma
Smoldering Plasma Cell Myeloma
Procedure: Autologous Hematopoietic Stem Cell Transplantation
Other: Laboratory Biomarker Analysis
Drug: Lenalidomide
Drug: Melphalan
Procedure: Peripheral Blood Stem Cell Transplantation
Other: Placebo
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: Arm I (melphalan, autologous PBSCT, lenalidomide)
Beginning between day 100-110, patients receive lenalidomide PO once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.
Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous PBSCT
Other Name: Autologous Stem Cell Transplantation
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Lenalidomide
Given PO
Other Names:
  • CC-5013
  • CC5013
  • CDC 501
  • LENALIDOMIDE
  • Revlimid
Drug: Melphalan
Given IV
Other Names:
  • Alanine Nitrogen Mustard
  • CB-3025
  • L-PAM
  • L-Phenylalanine Mustard
  • L-Sarcolysin
  • L-Sarcolysin Phenylalanine mustard
  • L-Sarcolysine
  • MELPHALAN
  • Melphalanum
  • Phenylalanine Mustard
  • Phenylalanine Nitrogen Mustard
  • Sarcoclorin
  • Sarkolysin
  • WR-19813
Procedure: Peripheral Blood Stem Cell Transplantation
Undergo autologous PBSCT
Other Names:
  • PBPC transplantation
  • Peripheral Blood Progenitor Cell Transplantation
  • Peripheral Stem Cell Support
  • Peripheral Stem Cell Transplantation
Placebo Comparator: Arm II (melphalan, autologous PBSCT, placebo)
Beginning between day 100-110, patients receive placebo PO once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.
Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous PBSCT
Other Name: Autologous Stem Cell Transplantation
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Melphalan
Given IV
Other Names:
  • Alanine Nitrogen Mustard
  • CB-3025
  • L-PAM
  • L-Phenylalanine Mustard
  • L-Sarcolysin
  • L-Sarcolysin Phenylalanine mustard
  • L-Sarcolysine
  • MELPHALAN
  • Melphalanum
  • Phenylalanine Mustard
  • Phenylalanine Nitrogen Mustard
  • Sarcoclorin
  • Sarkolysin
  • WR-19813
Procedure: Peripheral Blood Stem Cell Transplantation
Undergo autologous PBSCT
Other Names:
  • PBPC transplantation
  • Peripheral Blood Progenitor Cell Transplantation
  • Peripheral Stem Cell Support
  • Peripheral Stem Cell Transplantation
Other: Placebo
Given PO
Other Names:
  • placebo
  • placebo therapy
  • PLCB
  • sham therapy

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the efficacy of CC-5013 (lenalidomide) in prolonging time to disease progression in patients with multiple myeloma after autologous stem cell transplant (ASCT).

SECONDARY OBJECTIVES:

I. To determine if CC-5013 will increase the complete response (CR) rate in patients with multiple myeloma following ASCT.

II. To compare the progression-free survival (PFS) and overall survival (OS) in patients with multiple myeloma who have undergone ASCT and who then are randomized to either CC-5013 or placebo.

III. To determine the feasibility of long-term administration of CC-5013 to multiple myeloma patients who have undergone ASCT.

OUTLINE:

PERIPHERAL BLOOD STEM CELL (PBSC) MOBILIZATION: Mobilization of autologous PBSC will be performed according to institutional guidelines.

AUTOLOGOUS PBSC TRANSPLANTATION (PBSCT): Patients receive melphalan intravenously (IV) over 30-60 minutes on day -2 or -1 or over 2 days on days -3 and -2 or -2 and -1. Patients undergo autologous PBSCT on day 0.

Patients are then randomized to 1 of 2 maintenance treatment arms. (Note: As of 12/17/09, no more patients will be randomized between lenalidomide and placebo. Patients who have not been randomized as of 12/17/09 will be assigned to lenalidomide.)

ARM I: Beginning between day 100-110, patients receive lenalidomide orally (PO) once daily.

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

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

After completion of study treatment, patients are followed up every 3 months for 1 year and then 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:

  • Patients must have active multiple myeloma requiring treatment (Durie-Salmon stage >= 1) and have stable disease or be responsive to at least 2 months of any induction therapy; patients with smoldering myeloma are not eligible unless the disease has progressed to >= stage 1
  • No more than 12 months of any prior therapy, including CC-5013 and thalidomide
  • Within 12 months of initiation of induction therapy
  • No prior progression after initial therapy; in addition, no more than two regimens will be allowed excluding dexamethasone alone
  • No prior peripheral blood, bone marrow, or solid organ transplant
  • Patients must have peripheral blood stem cell collection of >= 2 x 10^6 cluster of differentiation (CD)34+ 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; peripheral blood stem cell collection may occur before or after registration
  • Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Patients must have diffusing capacity of the lung for carbon monoxide (DLCO) > 50% predicted with no symptomatic pulmonary disease
  • Patients must have left ventricular ejection fraction (LVEF) >= 40% by multi gated acquisition scan (MUGA) or echocardiogram
  • Patients must not have uncontrolled diabetes mellitus
  • Patients must not have an active serious infection
  • Patients must not be human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSag), or hepatitis (Hep) C positive
  • Patients must be non-pregnant and non-nursing; women of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL 10-14 days prior to registration and repeated within 24 hours prior to the first dose of lenalidomide; in addition, women of childbearing potential taking lenalidomide must have a pregnancy test performed by the doctor weekly during the first 4 weeks of treatment, and then every 4 weeks if menses are regular and every 2 weeks if menses are irregular, and then 30 days following the last dose of lenalidomide; women of childbearing potential must either commit to continued abstinence from heterosexual intercourse or begin two acceptable methods of birth control - one highly effective method (intrauterine device [IUD], hormonal, tubal ligation, or partner's vasectomy), and one additional effective method (latex condom, diaphragm, or cervical cap) - at the same time, at least 4 weeks before she begins lenalidomide therapy; "women of childbearing" potential is defined as a sexually mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months; men must agree not to father a child and must use a latex condom during any sexual contact with women of childbearing potential while taking lenalidomide and for 4 weeks after therapy is stopped, even if they have undergone a successful vasectomy
  • Absolute neutrophil count (ANC) >= 1000/uL
  • Platelets >= 100,000/uL
  • Creatinine clearance* >= 40 cc/min

    • To be calculated by method of Cockcroft-Gault or after 24-hour urine collection
  • Creatinine =< 2 mg/dL
  • Total bilirubin =< 2 mg/dL
  • Aspartate aminotransferase (AST) =< 3 x upper limits of normal
  • Alkaline phosphatase =< 3 x upper limits of normal
  • Urine (U)-human chorionic gonadotropin (HCG) or serum HCG negative (if patient of childbearing potential)
  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

  Show 114 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Philip McCarthy Alliance for Clinical Trials in Oncology
  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, U10CA180821, U10CA031946
Study First Received: June 13, 2005
Results First Received: March 28, 2013
Last Updated: July 29, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Lenalidomide
Mechlorethamine
Melphalan
Nitrogen Mustard Compounds
Thalidomide
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents

ClinicalTrials.gov processed this record on August 26, 2015