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
Overview
- Phase
- Phase 3
- Status
- Active, not recruiting
- Enrollment
- 460
- Locations
- 140
- Primary Endpoint
- Time to Progression
Overview
Brief Summary
This randomized phase III trial studies lenalidomide to see how well it works compared to a placebo in treating patients with multiple myeloma who are undergoing autologous stem cell transplant. 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.
Detailed Description
PRIMARY OBJECTIVE:
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Exclusion Criteria
- Not provided
Arms & Interventions
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.
Intervention: Autologous Hematopoietic Stem Cell Transplantation (Procedure)
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.
Intervention: Laboratory Biomarker Analysis (Other)
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.
Intervention: Lenalidomide (Drug)
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.
Intervention: Melphalan (Drug)
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.
Intervention: Peripheral Blood Stem Cell Transplantation (Procedure)
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.
Intervention: Autologous Hematopoietic Stem Cell Transplantation (Procedure)
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.
Intervention: Laboratory Biomarker Analysis (Other)
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.
Intervention: Melphalan (Drug)
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.
Intervention: Peripheral Blood Stem Cell Transplantation (Procedure)
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.
Intervention: Placebo Administration (Other)
Outcomes
Primary Outcomes
Time to Progression
Time Frame: Duration of study (up to 10years)
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 Outcomes
- Response to Autologous Hematopoietic Stem-cell Transplant (HSCT) at Day 100(Day 100)