Stem Cell Transplant With Lenalidomide Maintenance in Patients With Multiple Myeloma (BMT CTN 0702)

NCT ID: NCT01109004

Last Updated: 2021-12-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 758 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2018-03-03

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.

Conditions

Multiple Myeloma

Keywords

Symptomatic Multiple Myeloma; Lenalidomide; Anti-Myeloma Agents; Hematologic Disorders; Maintenance Therapy; Progression; Autologous Transplant; RVD Consolidation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tandem auto transplant

Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance

Group Type: ACTIVE_COMPARATOR

Lenalidomide

Intervention Type: DRUG

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 a second autologous PBSC transplant with the same conditioning regimen as the first transplant. All patients will also receive maintenance lenalidomide which will start after the second transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.

RVD consolidation

Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance

Group Type: ACTIVE_COMPARATOR

lenalidomide, bortezomib and dexamethasone

Intervention Type: DRUG

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 consolidation therapy with RVD (lenalidomide 15 mg/day on Days 1-14, dexamethasone 40mg on Days 1, 8 and 15, and bortezomib 1.3mg/m2 on Days 1, 4, 8 and 11 of every 21 day cycle, patients will receive four cycles). All patients will also receive maintenance lenalidomide which will start after consolidation therapy. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.

Lenalidomide maintenance

Initial autologous transplant followed by lenalidomide maintenance

Group Type: ACTIVE_COMPARATOR

Lenalidomide

Intervention Type: DRUG

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 maintenance with lenalidomide (15 mg daily). Maintenance lenalidomide will start after the first autologous transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.

Interventions

Lenalidomide

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 a second autologous PBSC transplant with the same conditioning regimen as the first transplant. All patients will also receive maintenance lenalidomide which will start after the second transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.

Intervention Type: DRUG

lenalidomide, bortezomib and dexamethasone

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 consolidation therapy with RVD (lenalidomide 15 mg/day on Days 1-14, dexamethasone 40mg on Days 1, 8 and 15, and bortezomib 1.3mg/m2 on Days 1, 4, 8 and 11 of every 21 day cycle, patients will receive four cycles). All patients will also receive maintenance lenalidomide which will start after consolidation therapy. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.

Intervention Type: DRUG

Lenalidomide

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 maintenance with lenalidomide (15 mg daily). Maintenance lenalidomide will start after the first autologous transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.

Intervention Type: DRUG

Other Intervention Names

Revlimid™; Revlimid™, Velcade®, and Decadron; Revlimid™

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.
• Patients with prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent less than 5 years previously will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs. Cancer treated with curative intent greater than 5 years previously is allowed.
• Female patients who are pregnant (positive B-HCG) or breastfeeding.
• Females of childbearing potential (FCBP) or men who have sexual contact with FCBP unwilling to use contraceptive techniques during the length of lenalidomide maintenance therapy.
• Prior allograft or prior autograft.
• Patients who have received mid-intensity melphalan (greater than 50 mg IV) as part of prior therapy.
• Patients unable or unwilling to provide informed consent.
• Prior organ transplant requiring immunosuppressive therapy.
• Patients with disease progression prior to enrollment.
• Patients who have received lenalidomide as initial therapy for MM and have experienced toxicities resulting in treatment discontinuation.
• Patients who experienced thromboembolic events while on full anticoagulation during prior therapy with lenalidomide or thalidomide.
• Patients unwilling to take deep vein thrombosis (DVT) prophylaxis.
• Patients who cannot undergo an intervention in any treatment arm due to a priori denial of medical costs coverage by third party payers.
• Patients unable to unwilling to return to the transplant center for their assigned treatments.

• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Blood and Marrow Transplant Clinical Trials Network

NETWORK

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mary Horowitz, MD

Role: STUDY_DIRECTOR

Center for International Blood and Marrow Transplant Research

Locations

Arizona Cancer Center

Tucson, Arizona, United States

City of Hope National Medical Center

Duarte, California, United States

UCSD Medical Center

La Jolla, California, United States

University of California, San Francisco

San Francisco, California, United States

Stanford Hospital and Clinics

Stanford, California, United States

Colorado Blood Cancer Institute

Denver, Colorado, United States

Christiana Care Health System

Newark, Delaware, United States

University of Florida College of Medicine

Gainesville, Florida, United States

Florida Hospital Cancer Institute

Orlando, Florida, United States

H. Lee Moffitt Cancer Center

Tampa, Florida, United States

Blood and Marrow Transplant Program at Northside Hospital

Atlanta, Georgia, United States

Georgia Health Sciences University

Augusta, Georgia, United States

St. Lukes Mountain States Tumor Institute

Boise, Idaho, United States

Rush University Medical Center

Chicago, Illinois, United States

University of Illinois

Chicago, Illinois, United States

Advocate Lutheran General Hospital

Park Ridge, Illinois, United States

University of Kansas Hospital

Kansas City, Kansas, United States

Wichita CCOP

Wichita, Kansas, United States

University of Kentucky

Lexington, Kentucky, United States

Louisiana State University Health Sciences Center

Shreveport, Louisiana, United States

DFCI, Brigham and Womens Hospital

Boston, Massachusetts, United States

DFCI, Massachusetts General Hospital

Boston, Massachusetts, United States

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Karmanos Cancer Institute/BMT

Detroit, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

Washington University, Barnes Jewish Hospital

St Louis, Missouri, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Roswell Park Cancer Center

Buffalo, New York, United States

North Shore University Hospital

Lake Success, New York, United States

Mount Sinai Medical Center

New York, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

University of North Carolina Hospital at Chapel Hill

Chapel Hill, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Jewish Hospital BMT Program

Cincinnati, Ohio, United States

University Hospitals of Cleveland

Cleveland, Ohio, United States

Ohio State/Arthur G. James Cancer Hospital

Columbus, Ohio, United States

University of Oklahoma Medical Center

Oklahoma City, Oklahoma, United States

Oregon Health & Science University

Portland, Oregon, United States

Penn State College of Medicine, The Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania, United States

Thompson Cancer Survival Center

Knoxville, Tennessee, United States

Sarah Cannon Blood & Marrow Transplant Program

Nashville, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Baylor College of Medicine/The Methodist Hospital

Houston, Texas, United States

University of Texas, MD Anderson CRC

Houston, Texas, United States

Texas Transplant Institute

San Antonio, Texas, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

West Virginia University Hospital

Morgantown, West Virginia, United States

University of Wisconsin Hospital & Clinics

Madison, Wisconsin, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

Stadtmauer EA, Pasquini MC, Blackwell B, Hari P, Bashey A, Devine S, Efebera Y, Ganguly S, Gasparetto C, Geller N, Horowitz MM, Koreth J, Knust K, Landau H, Brunstein C, McCarthy P, Nelson C, Qazilbash MH, Shah N, Vesole DH, Vij R, Vogl DT, Giralt S, Somlo G, Krishnan A. Autologous Transplantation, Consolidation, and Maintenance Therapy in Multiple Myeloma: Results of the BMT CTN 0702 Trial. J Clin Oncol. 2019 Mar 1;37(7):589-597. doi: 10.1200/JCO.18.00685. Epub 2019 Jan 17.

Reference Type: RESULT

PMID: 30653422 (View on PubMed)

Pasquini MC, Wallace PK, Logan B, Kaur M, Tario JD, Howard A, Zhang Y, Brunstein C, Efebera Y, Geller N, Giralt S, Hari P, Horowitz MM, Koreth J, Krishnan A, Landau H, Somlo G, Shah N, Stadtmauer E, Vogl DT, Vesole DH, McCarthy PL, Hahn T. Minimal Residual Disease Status in Multiple Myeloma 1 Year After Autologous Hematopoietic Cell Transplantation and Lenalidomide Maintenance Are Associated With Long-Term Overall Survival. J Clin Oncol. 2024 Aug 10;42(23):2757-2768. doi: 10.1200/JCO.23.00934. Epub 2024 May 3.

Reference Type: DERIVED

PMID: 38701390 (View on PubMed)

Other Identifiers

BMT CTN 0702

Identifier Type: OTHER

Identifier Source: secondary_id

U01HL069294-05

Identifier Type: NIH

Identifier Source: secondary_id

View Link

690

Identifier Type: OTHER

Identifier Source: secondary_id

BMTCTN0702

Identifier Type: -

Identifier Source: org_study_id

NCT02257515

Identifier Type: -

Identifier Source: nct_alias