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

• ClinicalTrials.gov Identifier: NCT02322320
• Recruitment Status: Completed
• First Posted: December 23, 2014
• Last Update Posted: September 11, 2019
• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Collaborators: Blood and Marrow Transplant Clinical Trials Network; National Cancer Institute (NCI); National Marrow Donor Program
• Information provided by (Responsible Party): National Heart, Lung, and Blood Institute (NHLBI)

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Drug: Lenalidomide	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 273 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Continued, Long-Term Follow-Up and Lenalidomide Maintenance Therapy for Patients on BMT CTN 0702 Protocol (BMT CTN #07LT)
• Actual Study Start Date: March 2015
• Actual Primary Completion Date: June 7, 2019
• Actual Study Completion Date: June 7, 2019

Arms and Interventions

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 Name: 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 Name: 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 Name: Revlimid™

Outcome Measures

Primary Outcome Measures :

1. Compare the PFS as a time to event analysis from randomization on the BMT CTN 0702 protocol between the three randomized treatment arms as a pairwise comparison. [ Time Frame: 5 years post randomization on BMT CTN 0702 ]
   The primary analysis will include all randomized subjects from the BMT CTN 0702 protocol, classified according to their randomized treatment allocation, irrespective of treatment actually received [intent-to-treat]. The time to this event is the time from randomization on the BMT CTN 0702 protocol to progression, initiation of non-protocol anti-myeloma therapy, or death from any cause. Patients will be censored at loss to follow-up or end of 2018, whichever comes first. Deaths without progression are treated as failures no matter when they occur. The analysis will be conducted once all living patients have been followed for 5-years post randomization on the BMT CTN 0702 protocol.

Secondary Outcome Measures :

1. Overall survival from randomization on the BMT CTN 0702 protocol [ Time Frame: 5 years post randomization on BMT CTN 0702 ]
   Overall survival (OS) time will be calculated as the time from randomization on the BMT CTN 0702 protocol to death, loss to follow-up or the end of the study, whichever comes first. Patients alive at the time of last observation or lost to follow-up will be censored at the date of last contact. OS will be compared between treatment arms.
2. Event-free survival from randomization on the BMT CTN 0702 protocol [ Time Frame: 5 years post randomization on BMT CTN 0702 ]
   Event-free survival (EFS) will be calculated as the time from randomization on the BMT CTN 0702 protocol to death, progression, second primary malignancy, loss to follow-up or the end of the study, whichever comes first. Patients alive at the time of last observation of lost to follow-up will be censored at the date of last contact. EFS will be compared between treatment arms.
3. Unexpected Grades 3 - 5 adverse events [ Time Frame: 5 years post randomization on BMT CTN 0702 ]
   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.
4. Health Quality of Life [ Time Frame: 5 years post randomization on BMT CTN 0702 ]
   Health quality of life (HQL) will be compared between all treatment groups utilizing the FACT-BMT and SF-36.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

  Show 42 Study Locations

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Blood and Marrow Transplant Clinical Trials Network

National Cancer Institute (NCI)

National Marrow Donor Program

Investigators

• Study Director: Mary Horowitz, MD; Center for International Blood and Marrow Transplant Research

More Information

Additional Information:

Blood and Marrow Transplant Clinical Trials Network  National Marrow Donor Program 

• Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
• ClinicalTrials.gov Identifier: NCT02322320 History of Changes
• Other Study ID Numbers: BMTCTN07LT; U01HL069294-05 ( U.S. NIH Grant/Contract )
• First Posted: December 23, 2014
• Last Update Posted: September 11, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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).
• Supporting Materials: Study Protocol; Informed Consent Form (ICF)
• Time Frame: Within 6 months of official study closure at participating sites.
• Access Criteria: Available to the public
• URL: https://biolincc.nhlbi.nih.gov/home/

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):

Multiple Myeloma; Lenalidomide; Maintenance Therapy; Progression; Long-term; Anti-Myeloma Agents; Hematologic Disorders

Additional relevant MeSH terms:

Lenalidomide; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Immunologic Factors; Physiological Effects of Drugs; Growth Substances; Growth Inhibitors; Antineoplastic Agents