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

Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02322320
• Other study ID #: BMTCTN07LT
• Secondary ID: U01HL069294-05
• Status: Completed
• Phase: Phase 3
• Start date: March 2015
• Est. completion date: June 7, 2019

Study information

• Verified date: September 2019
• Source: National Heart, Lung, and Blood Institute (NHLBI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 273
• Est. completion date: June 7, 2019
• Est. primary completion date: June 7, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma

Intervention

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.

Locations

Country	Name	City	State
United States	University of Michigan Medical Center	Ann Arbor	Michigan
United States	BMT Group of Georgia (Northside Hospital)	Atlanta	Georgia
United States	DFCI, Brigham and Womens 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	Jewish Hospital BMT Program	Cincinnati	Ohio
United States	University Hospitals of Cleveland/Case Western	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	University of Texas/MD Anderson CRC	Houston	Texas
United States	University of Kansas Hospital	Kansas City	Kansas
United States	University of California, San Diego Medical Center	La Jolla	California
United States	North Shore University Hospital	Lake Success	New York
United States	University of Wisconsin Hospital & Clinics	Madison	Wisconsin
United States	University of Miami	Miami	Florida
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	University of Oklahoma Medical Center	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Washington University, Barnes Jewish Hospital	Saint Louis	Missouri
United States	Texas Transplant Institute	San Antonio	Texas
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	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (4)

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

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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

External Links

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