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

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Lenalidomide

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).

• Study Type: Interventional
• Enrollment (Actual): 273
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Arizona Cancer Center
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope National Medical Center
    • La Jolla, California, United States, 92093
      • University of California, San Diego Medical Center
    • Stanford, California, United States, 94305
      • Stanford Hospital and Clinics
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida College of Medicine
    • Miami, Florida, United States, 33624
      • University of Miami
    • Tampa, Florida, United States, 33624
      • H. Lee Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • BMT Group of Georgia (Northside Hospital)
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Hospital
  • Louisiana
    • Shreveport, Louisiana, United States, 71130
      • Louisiana State University Health Sciences Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • DFCI, Brigham and Womens Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48105-2967
      • University of Michigan Medical Center
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute/BMT
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University, Barnes Jewish Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198-7680
      • University of Nebraska Medical Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Center
    • Lake Success, New York, United States, 11042
      • North Shore University Hospital
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
    • New York, New York, United States, 10174
      • Memorial Sloan-Kettering Cancer Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7305
      • University of North Carolina Hospital at Chapel Hill
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Jewish Hospital BMT Program
    • Cleveland, Ohio, United States, 44106-5061
      • University Hospitals of Cleveland/Case Western
    • Columbus, Ohio, United States, 43210
      • Ohio State/Arthur G. James Cancer Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239-3098
      • Oregon Health & Science University
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State College of Medicine, The Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Blood & Marrow Transplant Program
    • Nashville, Tennessee, United States, 37232-8210
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • University of Texas/MD Anderson CRC
    • San Antonio, Texas, United States, 78229
      • Texas Transplant Institute
  • Washington
    • Seattle, Washington, United States, 98109-1024
      • Fred Hutchinson Cancer Research Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Hospital
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-5156
      • University of Wisconsin Hospital & Clinics
    • Milwaukee, Wisconsin, United States, 53211
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tandem Auto Transplant; Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance	Drug: Lenalidomide; In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.; Other Names: Revlimid™
Active Comparator: RVD Consolidation; Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance	Drug: Lenalidomide; In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.; Other Names: Revlimid™
Active Comparator: Lenalidomide Maintenance; Initial autologous transplant followed by lenalidomide maintenance	Drug: Lenalidomide; In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.; Other Names: Revlimid™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Progression-free Survival (PFS)	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.	5 years post-randomization in BMT CTN 0702

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Overall Survival (OS)	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.	5 years post-randomization in BMT CTN 0702
Percentage of Participants With Event-free Survival (EFS)	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.	5 years post-randomization in BMT CTN 0702
Percentage of Participants With Secondary Primary Malignancies (SPM)	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.	5 years post-randomization in BMT CTN 0702
Percentage of Participants With Disease Progression	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.	5 years post-randomization in BMT CTN 0702

Collaborators and Investigators

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Collaborators: National Cancer Institute (NCI); National Marrow Donor Program; Blood and Marrow Transplant Clinical Trials Network

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2015
• Primary Completion (Actual): June 7, 2019
• Study Completion (Actual): June 7, 2019

Study Registration Dates

• First Submitted: December 17, 2014
• First Submitted That Met QC Criteria: December 17, 2014
• First Posted (Estimate): December 23, 2014

Study Record Updates

• Last Update Posted (Actual): May 11, 2020
• Last Update Submitted That Met QC Criteria: April 27, 2020
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Progression; Multiple Myeloma; Lenalidomide; Long-term; Maintenance Therapy; Anti-Myeloma Agents; Hematologic Disorders
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Multiple Myeloma; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide
• Other Study ID Numbers: BMTCTN07LT; U01HL069294-05 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Results will be published in a manuscript and supporting information submitted to NIH BioLINCC (including data dictionaries, case report forms, data submission documentation, documentation for outcomes dataset, etc where indicated).
• IPD Sharing Time Frame: Within 6 months of official study closure at participating sites.
• IPD Sharing Access Criteria: Available to the public
• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF)