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Continued, Long-Term Follow-Up and Lenalidomide Maintenance Therapy for Patients on BMT CTN 0702 Protocol (BMT CTN 07LT)

Phase 3
Completed
Conditions
Multiple Myeloma
Interventions
Registration Number
NCT02322320
Lead Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Brief Summary

This study is designed to compare long-term outcomes among patients randomized on the BMT CTN 0702 protocol (NCT01109004), "A Trial of Single Autologous Transplant with or without Consolidation Therapy versus Tandem Autologous Transplant with Lenalidomide Maintenance for Patients with Multiple Myeloma". It is hypothesized that use of novel anti-myeloma agents will improve long-term progression-free survival (PFS) after high-dose melphalan followed by autologous hematopoietic cell transplantation (HCT) as compared to a second autologous transplantation.

Detailed Description

This study is designed to compare long-term outcomes among patients randomized on the BMT CTN 0702 protocol (NCT01109004). All patients who consent will be followed for death, progression, Second Primary Malignancies (SPMs), and Quality of Life (QOL). Patients who do not consent to the long-term follow-up mechanism or who have experienced progression on the BMT CTN 0702 study will be followed through the standard Center for International Blood and Marrow Transplant Research (CIBMTR) long-term follow-up mechanism. Additionally, patients who are eligible and are willing to continue with lenalidomide as maintenance therapy will be provided lenalidomide free of charge. These patients will continue to receive lenalidomide as maintenance therapy until disease progression or discontinuation due to toxicity, death, or withdrawal from the study. The endpoints assessed will include progression-free survival (PFS), overall survival (OS), event-free survival (EFS), incidence of second primary malignancies (SPM) and health quality of life (QOL).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
273
Inclusion Criteria

Patients fulfilling the following criteria will be eligible to provide continued long-term follow-up data as part of this study:

  1. Enrolled and randomized on the BMT CTN 0702 protocol.
  2. Alive at the completion of BMT CTN 0702 protocol specified follow-up defined as 4 years post-randomization.
  3. Patients without evidence of disease progression at the completion of BMT CTN 0702 protocol specified follow up.
  4. Signed Informed Consent Form.
  5. Patients with the ability to speak English or Spanish are eligible to participate in the HQL component of this trial.

Inclusion Criteria for Optional Long-term Lenalidomide Maintenance Therapy:

Patients fulfilling the following criteria will be eligible to provide continued long-term follow-up data AND receive long-term lenalidomide maintenance therapy as part of this study:

  1. Enrolled and randomized to BMT CTN 0702.
  2. Completion of 3 years of maintenance therapy on BMT CTN 0702.
  3. Registered in the mandatory Revlimid REMS® program (formerly the RevAssist® for Study Participants (RASP) program), and be willing and able to comply with the requirements of the Revlimid REMS® program, including counseling, pregnancy testing, and phone surveys.
  4. Signed informed consent form.
  5. Patients with the ability to speak English or Spanish are eligible to participate in the HQL component of this trial.
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Exclusion Criteria

Patients who meet any of the following criteria will be ineligible to receive long-term lenalidomide maintenance therapy as part of this study:

  1. Patients who have evidence of disease progression prior to enrollment.
  2. Patients who were discontinued from BMT CTN 0702 lenalidomide maintenance therapy, for any reason, prior to the completion of the 3 years of 0702 maintenance.
  3. Female patients who are pregnant (positive - Beta Human Chorionic Gonadotropin) or breastfeeding.
  4. 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.
  5. Patients who experienced thromboembolic events while on full anticoagulation during prior therapy with lenalidomide.
  6. Patients unwilling to take Deep Vein Thrombosis (DVT) prophylaxis.
  7. Patients who developed a second primary malignancy, excluding non-melanoma skin cancers after initiation of lenalidomide maintenance therapy on BMT CTN 0702.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Tandem Auto TransplantLenalidomideInitial autologous transplant followed by a second autologous transplant and lenalidomide maintenance
RVD ConsolidationLenalidomideInitial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance
Lenalidomide MaintenanceLenalidomideInitial autologous transplant followed by lenalidomide maintenance
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With Progression-free Survival (PFS)5 years post-randomization in BMT CTN 0702

This analysis includes all randomized subjects from the BMT CTN 0702 protocol classified according to their randomized treatment assignment (intention-to-treat). 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, the Kaplan-Meier estimator was used to estimate progression-free survival during the 5 year post-randomization follow-up period.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With Overall Survival (OS)5 years post-randomization in BMT CTN 0702

This analysis includes all randomized subjects from the BMT CTN 0702 protocol classified according to their randomized treatment assignment (intention-to-treat). Overall survival is defined as survival of death from any cause. To account for loss to follow-up, the Kaplan-Meier estimator was used to estimate overall survival during the 5 year post-randomization follow-up period.

Percentage of Participants With Secondary Primary Malignancies (SPM)5 years post-randomization in BMT CTN 0702

This analysis includes all randomized subjects from the BMT CTN 0702 protocol classified according to their randomized treatment assignment (intention-to-treat). SPM is defined as development of any second malignancy, excluding non-melanoma skin cancers. To account for loss to follow-up, the Aalen-Johansen estimator was used to estimate the cumulative incidence of SPM during the 5 year post-randomization follow-up period.

The development of any SPMs excludes non-melanoma skin cancers. Death without SPMs will be considered a competing risk for this event. The cumulative incidence of SPMs will be compared between treatment arms.

Percentage of Participants With Disease Progression5 years post-randomization in BMT CTN 0702

This analysis includes all randomized subjects from BMT CTN 0702, classified by their treatment assignment (intention-to-treat). Disease progression is defined as progression of multiple myeloma, including one or more of the following:

* Reappearance of serum monoclonal paraprotein at a level \>= 0.5 g/dL

* 24-hour urine protein electrophoresis of at least 200mg paraprotein/24 hours

* Abnormal free light chain levels of \>10 mg/dl, only in patients without measurable paraprotein in serum and urine

* At least 10% plasma cells in a bone marrow aspirate or 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 other causes

To account for loss to follow-up, the Aalen-Johansen estimator was used to estimate the cumulative incidence of progression during the follow-up period.

Percentage of Participants With Event-free Survival (EFS)5 years post-randomization in BMT CTN 0702

This analysis includes all randomized subjects from the BMT CTN 0702 protocol classified according to their randomized treatment assignment (intention-to-treat). Event-free survival is defined as survival without disease progression, second primary malignancy, and death. To account for loss to follow-up, the Kaplan-Meier estimator was used to estimate event-free survival during the 5 year post-randomization follow-up period.

Trial Locations

Locations (42)

University of Pennsylvania Cancer Center

🇺🇸

Philadelphia, Pennsylvania, United States

University of Texas Southwestern Medical Center

🇺🇸

Dallas, Texas, United States

BMT Group of Georgia (Northside Hospital)

🇺🇸

Atlanta, Georgia, United States

Rush University Medical Center

🇺🇸

Chicago, Illinois, United States

DFCI, Brigham and Womens Hospital

🇺🇸

Boston, Massachusetts, United States

University Hospitals of Cleveland/Case Western

🇺🇸

Cleveland, Ohio, United States

Arizona Cancer Center

🇺🇸

Tucson, Arizona, United States

City of Hope National Medical Center

🇺🇸

Duarte, California, United States

Fred Hutchinson Cancer Research Center

🇺🇸

Seattle, Washington, United States

Jewish Hospital BMT Program

🇺🇸

Cincinnati, Ohio, United States

University of California, San Diego Medical Center

🇺🇸

La Jolla, California, United States

Stanford Hospital and Clinics

🇺🇸

Stanford, California, United States

University of Florida College of Medicine

🇺🇸

Gainesville, Florida, United States

Louisiana State University Health Sciences Center

🇺🇸

Shreveport, Louisiana, United States

University of Kansas Hospital

🇺🇸

Kansas City, Kansas, United States

Washington University, Barnes Jewish Hospital

🇺🇸

Saint Louis, Missouri, 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

Ohio State/Arthur G. James Cancer Hospital

🇺🇸

Columbus, Ohio, United States

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

🇺🇸

Hershey, Pennsylvania, United States

University of Texas/MD Anderson CRC

🇺🇸

Houston, Texas, United States

West Virginia University Hospital

🇺🇸

Morgantown, West Virginia, United States

University of Wisconsin Hospital & Clinics

🇺🇸

Madison, Wisconsin, United States

University of Miami

🇺🇸

Miami, Florida, United States

Hackensack University Medical Center

🇺🇸

Hackensack, New Jersey, United States

Memorial Sloan-Kettering Cancer Center

🇺🇸

New York, New York, United States

Colorado Blood Cancer Institute

🇺🇸

Denver, Colorado, United States

University of North Carolina Hospital at Chapel Hill

🇺🇸

Chapel Hill, North Carolina, United States

Karmanos Cancer Institute/BMT

🇺🇸

Detroit, Michigan, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

H. Lee Moffitt Cancer Center

🇺🇸

Tampa, Florida, United States

University of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

Sarah Cannon Blood & Marrow Transplant Program

🇺🇸

Nashville, Tennessee, United States

Vanderbilt University Medical Center

🇺🇸

Nashville, Tennessee, United States

Texas Transplant Institute

🇺🇸

San Antonio, Texas, United States

Medical College of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

University of Michigan Medical Center

🇺🇸

Ann Arbor, Michigan, United States

Wake Forest University Health Sciences

🇺🇸

Winston-Salem, North Carolina, United States

University of Nebraska Medical Center

🇺🇸

Omaha, Nebraska, United States

University of Oklahoma Medical Center

🇺🇸

Oklahoma City, Oklahoma, United States

Oregon Health & Science University

🇺🇸

Portland, Oregon, United States

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