Clinical trial NCT01109004: Stem Cell Transplant With Lenalidomide Maintenance in Patients With Multiple Myeloma (BMT CTN 0702)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: Symptomatic Multiple Myeloma
Lenalidomide
Anti-Myeloma Agents
Hematologic Disorders
Maintenance Therapy
Progression
Autologous Transplant
RVD Consolidation
Lead sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Sponsor class: NIH
Collaborators: name: Blood and Marrow Transplant Clinical Trials Network
name: National Cancer Institute (NCI)
First posted: 2010-04-22
Enrollment: 758
Sex: ALL
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percentage of Participants With Progression-free Survival (PFS)
timeFrame: 38 months post-randomization
Secondary outcomes:
measure: Percentage of Participants With Disease Progression
timeFrame: 38 months post-randomization
measure: Percentage of Participants With Overall Survival (OS)
timeFrame: 38 months post-randomization
measure: Percentage of Participants With Treatment-related Mortality (TRM)
timeFrame: Up to 38 months post-randomization
measure: Number of Participants With Treatment Response
timeFrame: 1 and 2 years post-randomization
measure: FACT-G Total Score
timeFrame: Up to 3 years post-randomization
measure: FACT-BMT Score
timeFrame: Up to 3 years post-randomization
measure: FACT-BMT Trial Outcome Index
timeFrame: Up to 3 years post-randomization
measure: MOS SF-36 Physical Component Summary
timeFrame: Up to 3 years post-randomization
measure: MOS SF-36 Mental Component Summary
timeFrame: Up to 3 years post-randomization
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: La Jolla
country: United States
facility: UCSD Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Stanford
country: United States
facility: Stanford Hospital and Clinics
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Newark
country: United States
facility: Christiana Care Health System
state: Delaware
city: Gainesville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Blood and Marrow Transplant Program at Northside Hospital
state: Georgia
city: Augusta
country: United States
facility: Georgia Health Sciences University
state: Georgia
city: Boise
country: United States
facility: St. Lukes Mountain States Tumor Institute
state: Idaho
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Lutheran General Hospital
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Hospital
state: Kansas
city: Wichita
country: United States
facility: Wichita CCOP
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Shreveport
country: United States
facility: Louisiana State University Health Sciences Center
state: Louisiana
city: Boston
country: United States
facility: DFCI, Brigham and Womens Hospital
state: Massachusetts
city: Boston
country: United States
facility: DFCI, Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute/BMT
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University, Barnes Jewish Hospital
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Center
state: New York
city: Lake Success
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Hospital at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cincinnati
country: United States
facility: Jewish Hospital BMT Program
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Columbus
country: United States
facility: Ohio State/Arthur G. James Cancer Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Medical Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Hershey
country: United States
facility: Penn State College of Medicine, The Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
city: Knoxville
country: United States
facility: Thompson Cancer Survival Center
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Blood & Marrow Transplant Program
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine/The Methodist Hospital
state: Texas
city: Houston
country: United States
facility: University of Texas, MD Anderson CRC
state: Texas
city: San Antonio
country: United States
facility: Texas Transplant Institute
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Hospital
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin Hospital & Clinics
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Center for International Blood and Marrow Transplant Research
name: Mary Horowitz, MD
role: STUDY_DIRECTOR
References:
citation: 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.