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

Study Overview
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Brief Summary
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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
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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).

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

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Lenalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients fulfilling the following criteria will be eligible to provide continued long-term follow-up data as part of this study: Enrolled and randomized on the BMT CTN 0702 protocol. Alive at the completion of BMT CTN 0702 protocol specified follow-up defined as 4 years post-randomization. Patients without evidence of disease progression at the completion of BMT CTN 0702 protocol specified follow up. Signed Informed Consent Form. 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: Enrolled and randomized to BMT CTN 0702. Completion of 3 years of maintenance therapy on BMT CTN 0702. 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. Signed informed consent form. 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: Patients who have evidence of disease progression prior to enrollment. 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. Female patients who are pregnant (positive - Beta Human Chorionic Gonadotropin) 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. Patients who experienced thromboembolic events while on full anticoagulation during prior therapy with lenalidomide. Patients unwilling to take Deep Vein Thrombosis (DVT) prophylaxis. Patients who developed a second primary malignancy, excluding non-melanoma skin cancers after initiation of lenalidomide maintenance therapy on BMT CTN 0702.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tandem Auto Transplant<br>Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance | Drug: Lenalidomide<br>* 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.<br>* Other names: Revlimid™;|
| Active Comparator: RVD Consolidation<br>Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance | Drug: Lenalidomide<br>* 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.<br>* Other names: Revlimid™;|
| Active Comparator: Lenalidomide Maintenance<br>Initial autologous transplant followed by lenalidomide maintenance | Drug: Lenalidomide<br>* 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.<br>* Other names: Revlimid™;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, Lenalidomide, Maintenance Therapy, Progression, Long-term, Anti-Myeloma Agents, Hematologic Disorders