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

Multiple Myeloma Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01109004
• Other study ID #: BMTCTN0702
• Secondary ID: BMT CTN 0702U01H
• Status: Completed
• Phase: Phase 3
• Start date: May 2010
• Est. completion date: March 3, 2018

Study information

• Verified date: December 2021
• Source: National Heart, Lung, and Blood Institute (NHLBI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT02257515

Recruitment information / eligibility

• Status: Completed
• Enrollment: 758
• Est. completion date: March 3, 2018
• Est. primary completion date: January 15, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

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 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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	University of Michigan Medical Center	Ann Arbor	Michigan
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	DFCI, Brigham and Womens Hospital	Boston	Massachusetts
United States	DFCI, Massachusetts General Hospital	Boston	Massachusetts
United States	Roswell Park Cancer Center	Buffalo	New York
United States	University of North Carolina Hospital at Chapel Hill	Chapel Hill	North Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
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 Texas Southwestern Medical Center	Dallas	Texas
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Karmanos Cancer Institute/BMT	Detroit	Michigan
United States	City of Hope National Medical Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Florida College of Medicine	Gainesville	Florida
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Penn State College of Medicine, The Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Baylor College of Medicine/The Methodist Hospital	Houston	Texas
United States	University of Texas, MD Anderson CRC	Houston	Texas
United States	University of Kansas Hospital	Kansas City	Kansas
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	UCSD Medical Center	La Jolla	California
United States	North Shore University Hospital	Lake Success	New York
United States	University of Kentucky	Lexington	Kentucky
United States	University of Wisconsin Hospital & Clinics	Madison	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	West Virginia University Hospital	Morgantown	West Virginia
United States	Sarah Cannon Blood & Marrow Transplant Program	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	Christiana Care Health System	Newark	Delaware
United States	University of Oklahoma Medical Center	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Florida Hospital Cancer Institute	Orlando	Florida
United States	Advocate Lutheran General Hospital	Park Ridge	Illinois
United States	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	University of Rochester Medical Center	Rochester	New York
United States	Washington University, Barnes Jewish Hospital	Saint Louis	Missouri
United States	Texas Transplant Institute	San Antonio	Texas
United States	University of California, San Francisco	San Francisco	California
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Louisiana State University Health Sciences Center	Shreveport	Louisiana
United States	Stanford Hospital and Clinics	Stanford	California
United States	H. Lee Moffitt Cancer Center	Tampa	Florida
United States	Arizona Cancer Center	Tucson	Arizona
United States	Wichita CCOP	Wichita	Kansas
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
National Heart, Lung, and Blood Institute (NHLBI)	Blood and Marrow Transplant Clinical Trials Network, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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, Soml — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Progression-free Survival (PFS)	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.	38 months post-randomization
Secondary	Percentage of Participants With Disease Progression	Disease Progression is defined as progression of multiple myeloma, including one or more of the following: A reappearance of serum monoclonal paraprotein, with a level of at least 0.5 g/dL; 24-hour urine protein electrophoresis with at least 200 mg paraprotein/24 hours; Abnormal free light chain levels of >10 mg/dl, only in patients without measurable paraprotein in the serum and urine; At least 10% plasma cells in a bone marrow aspirate or on trephine biopsy; Definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of new bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum Ca >11.5 mg/dL or >2.8 mmol/L) not attributable to any other cause; To account for loss to follow-up of a few participants, the cumulative incidence of TRM at 38 months post-randomization was estimated using the Aalen-Johansen estimator, treating death prior to disease progression as a competing risk.	38 months post-randomization
Secondary	Percentage of Participants With Overall Survival (OS)	Overall survival is defined as survival of death from any cause. To account for loss to follow-up of a few participants, the Kaplan-Meier estimator was used to estimate overall survival at 38 months post-randomization.	38 months post-randomization
Secondary	Percentage of Participants With Treatment-related Mortality (TRM)	TRM is defined as death prior to progression of multiple myeloma. To account for loss to follow-up of a few participants, the cumulative incidence of TRM at 38 months post-randomization was estimated using the Aalen-Johansen estimator, treating disease progression as a competing risk.	Up to 38 months post-randomization
Secondary	Number of Participants With Treatment Response	The number of participants with very good partial response (VGPR) or better [complete response (CR), near CR (nCR), and stringent CR (sCR)] according to the International Uniform Response Criteria will be calculated. The "Worse than VGPR" group includes PR, stable disease, and progressive disease.; sCR requires, in addition to CR: Normal free light chain ratio (FLC), Absence of clonal cells in bone marrow CR requires, in addition to nCR: Absence of the original monoclonal paraprotein (PPN), Disappearance of soft tissue plasmacytomas nCR is defined as: < 5% plasma cells in a bone marrow aspirate, No increase in lytic bone lesions VGPR requires: Serum or urine PPN not detectable on electrophoresis OR >=90% reduction in serum PPN plus urine PPN <100 mg/24hrs, >= 50% reduction in the level of serum monoclonal PPN or reduction in 24 hour urinary monoclonal PPN either >= 90% or to <200 mg/24 hours in light chain disease, >= 50% reduction in the size of soft tissue plasmacytomas	1 and 2 years post-randomization
Secondary	FACT-G Total Score	The Functional Assessment of Cancer Therapy-General (FACT-G) is a quality of life instrument that assesses the effects of cancer therapy on a patient's physical, social/family, emotional, and functional well-being. The assessment has 27 questions, each scored on a Likert scale from 0-4. The overall score is computed by adding scores of the questions and falls in the range 0-108, with higher scores indicating higher levels of overall well-being.	Up to 3 years post-randomization
Secondary	FACT-BMT Score	The Functional Assessment of Cancer Therapy-Bone Marrow Transplant scale (FACT-BMT) is a quality of life instrument that assesses the effects of bone marrow transplantation (BMT) on a patient's physical, social/family, emotional, and functional well-being while taking into consideration BMT-specific concerns. The assessment has 37 questions, each scored on a Likert scale from 0-4. The overall score is computed by adding scores of the questions and falls in the range 0-148, with higher scores indicating higher levels of overall well-being.	Up to 3 years post-randomization
Secondary	FACT-BMT Trial Outcome Index	The Functional Assessment of Cancer Therapy (FACT) Trial Outcome Index is a quality of life instrument that assesses the impact of bone marrow transplantation (BMT) on a patient's physical and functional well-being while taking into consideration BMT-specific concerns. The assessment has 24 questions, each scored on a Likert scale from 0-4. The overall score is computed by adding scores of the questions and falls in the range 0-96, with higher scores indicating higher levels of overall well-being.	Up to 3 years post-randomization
Secondary	MOS SF-36 Physical Component Summary	The Medical Outcome Study (MOS) SF-36 Physical Component Summary is a subscale of the SF-36 intended to measure physical well-being. It is scored on a scale of 0-100, with higher scores indicating higher levels of well-being.	Up to 3 years post-randomization
Secondary	MOS SF-36 Mental Component Summary	The Medical Outcome Study (MOS) SF-36 Mental Component Summary is a subscale of the SF-36 intended to measure mental well-being. It is scored on a scale of 0-100, with higher scores indicating higher levels of well-being.	Up to 3 years post-randomization

External Links

•   Blood and Marrow Transplant Clinical Trials Network Website
•   National Marrow Donor Program