A Trial of Single Autologous Transplant With or Without Consolidation Therapy Versus Tandem Autologous Transplant With Lenalidomide Maintenance for Patients With Multiple Myeloma (BMT CTN 0702)
Overview
- Phase
- Phase 3
- Intervention
- Lenalidomide
- Conditions
- Multiple Myeloma
- Sponsor
- National Heart, Lung, and Blood Institute (NHLBI)
- Enrollment
- 758
- Locations
- 54
- Primary Endpoint
- Percentage of Participants With Progression-free Survival (PFS)
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The study is designed as a Phase III, multicenter trial of tandem autologous transplants plus maintenance therapy versus the strategy of single autologous transplant plus consolidation therapy with lenalidomide, bortezomib and dexamethasone (RVD) followed by maintenance therapy or single autologous transplant plus maintenance therapy as part of upfront treatment of multiple myeloma (MM). Lenalidomide will be used as maintenance therapy for three years in all arms.
Detailed Description
The primary objective of the randomized trial is to compare three-year progression-free survival (PFS) between the three treatment arms as a pairwise comparison. Mobilization therapy will not be specified for the study. Randomization to three treatment arms will be done prior to the first transplants. All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m\^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive either a second autologous PBSC transplant with the same conditioning regimen as the first transplant or consolidation therapy with RVD (lenalidomide 15 mg/day on Days 1-14, dexamethasone 40 mg on Days 1, 8 and 15, and bortezomib 1.3mg/m\^2 on Days 1, 4, 8 and 11 of every 21 day cycle, patients will receive four cycles) or maintenance with lenalidomide (15 mg daily). All patients will also receive maintenance lenalidomide which will start after the second transplant, after the first autologous transplant or after consolidation therapy depending on the treatment arm. Maintenance therapy with lenalidomide will start at 10 mg daily for three months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients meeting the criteria for symptomatic multiple myeloma (MM).
- •Patients who are 70 years of age, or younger, at time of enrollment.
- •Patients who have received at least two cycles of any regimen as initial systemic therapy and are within 2 - 12 months of the first dose of initial therapy.
- •Cardiac function: left ventricular ejection fraction at rest greater than 40 percent.
- •Hepatic: bilirubin less than 1.5x the upper limit of normal and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than 2.5x the upper limit of normal. (Patients who have been diagnosed with Gilbert's Disease are allowed to exceed the defined bilirubin value of 1.5x the upper limit of normal.)
- •Renal: Creatinine clearance of grater than or equal to 40 mL/min, estimated or calculated.
- •Pulmonary: Diffusing capacity of the lung for carbon monoxide (DLCO), forced expiratory volume in one second (FEV1), or forced vital capacity (FVC) greater than 50 percent of predicted value (corrected for hemoglobin).
- •Patients with an adequate autologous graft defined as a cryopreserved PBSC graft containing greater than or equal to 4 x 10\^6 CD34+ cells/kg patient weight. The graft may not be CD34+ selected or otherwise manipulated to remove tumor or other cells. The graft can be collected at the transplanting institution or by a referring center. The autograft must be stored so that there are two products each containing at least 2 x 10\^6 CD34+ cells/kg patient weight.
- •Signed informed consent form.
Exclusion Criteria
- •Patients who never fulfill the criteria for symptomatic MM.
- •Patients with purely non-secretory MM \[absence of a monoclonal protein (M protein) in serum as measured by electrophoresis and immunofixation and the absence of Bence Jones protein in the urine defined by use of conventional electrophoresis and immunofixation techniques\]. Patients with light chain MM detected in the serum by free light chain assay are eligible.
- •Patients with plasma cell leukemia.
- •Karnofsky performance score less than 70 percent.
- •Patients with greater than grade 2 sensory neuropathy (CTCAE).
- •Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and progression of clinical symptoms).
- •Patients seropositive for the human immunodeficiency virus (HIV).
- •Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
- •Patient has hypersensitivity to bortezomib, boron or mannitol.
- •Patient has received other investigational drugs with 14 days before enrollment.
Arms & Interventions
Tandem auto transplant
Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance
Intervention: Lenalidomide
RVD consolidation
Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance
Intervention: lenalidomide, bortezomib and dexamethasone
Lenalidomide maintenance
Initial autologous transplant followed by lenalidomide maintenance
Intervention: Lenalidomide
Outcomes
Primary Outcomes
Percentage of Participants With Progression-free Survival (PFS)
Time Frame: 38 months post-randomization
Progression-free survival is defined as survival without disease progression or initiation of non-protocol anti-myeloma therapy. To account for loss to follow-up of a few participants, the Kaplan-Meier estimator was used to estimate progression-free survival at 38 months post-randomization.
Secondary Outcomes
- Percentage of Participants With Disease Progression(38 months post-randomization)
- Number of Participants With Treatment Response(1 and 2 years post-randomization)
- Percentage of Participants With Overall Survival (OS)(38 months post-randomization)
- FACT-BMT Score(Up to 3 years post-randomization)
- Percentage of Participants With Treatment-related Mortality (TRM)(Up to 38 months post-randomization)
- MOS SF-36 Physical Component Summary(Up to 3 years post-randomization)
- MOS SF-36 Mental Component Summary(Up to 3 years post-randomization)
- FACT-G Total Score(Up to 3 years post-randomization)
- FACT-BMT Trial Outcome Index(Up to 3 years post-randomization)