Allo vs Hypomethylating/Best Supportive Care in MDS (BMTCTN1102)

NCT ID: NCT02016781

Last Updated: 2023-03-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 384 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-16
• Study Completion Date: 2021-10-05

Brief Summary

This study is designed as a multicenter trial, with biological assignment to one of two study arms; Arm 1: Reduced intensity conditioning allogeneic hematopoietic cell transplantation (RIC-alloHCT), Arm 2: Non-Transplant Therapy/Best Supportive Care.

Detailed Description

Background: MDS is a clonal disorder of hematopoietic precursors and stem cells, which may evolve to a terminal phase resembling acute leukemia. A subject of clinical urgency for researchers, clinicians, patients, and health care underwriters such as Medicare, is the role of allogeneic hematopoietic cell transplantation (alloHCT) in the treatment of older patients with higher risk myelodysplastic syndromes (MDS). The use of reduced intensity conditioning (RIC) regimens has extended HCT to the care of older patients with acute myelogenous leukemia (AML) and lymphoma and a number of retrospective and phase II trials for patients with MDS now show the curative potential of RIC alloHCT in selected patients.

This protocol is designed to evaluate the relative benefits of RIC alloHCT compared to non-transplant therapies focusing on overall survival. This will be done by having patients biologically assigned to the alloHCT arm or the hypomethylating therapy/best supportive care arm and following them for survival at 3 years.

Conditions

MDS

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Transplant

Reduced intensity conditioning allogeneic hematopoietic cell transplantation (RIC-alloHCT)

Group Type: ACTIVE_COMPARATOR

Allogeneic Hematopoietic Cell Transplant

Intervention Type: PROCEDURE

Bone marrow or peripheral blood stem cell transplant.from a fully matched related (6/6) or unrelated (8/8) donor. The specific transplant treatment regimen will be at the discretion of the treating physician but is required to be reduced-intensity.

Hypomethylating Therapy / Best Supportive Care

The specific non-transplant treatment regimen will be at the discretion of the treating physician.

Group Type: ACTIVE_COMPARATOR

Hypomethylating Therapy / Best Supportive Care

Intervention Type: PROCEDURE

The specific non-transplant treatment regimen will be at the discretion of the treating physician.

Interventions

Allogeneic Hematopoietic Cell Transplant

Bone marrow or peripheral blood stem cell transplant.from a fully matched related (6/6) or unrelated (8/8) donor. The specific transplant treatment regimen will be at the discretion of the treating physician but is required to be reduced-intensity.

Intervention Type: PROCEDURE

Hypomethylating Therapy / Best Supportive Care

The specific non-transplant treatment regimen will be at the discretion of the treating physician.

Intervention Type: PROCEDURE

Other Intervention Names

RIC alloHCT; Non-transplant

Eligibility Criteria

Inclusion Criteria

• Patients fulfilling the following criteria will be eligible for entry into this study:

1. Patients with de novo MDS who have, or have previously had, Intermediate-2 or High risk disease as determined by the International Prognostic Scoring System (IPSS). Current Intermediate-2 or High risk disease is NOT a requirement.

2. Patients must have an acceptable MDS subtype:

• Refractory cytopenia with unilineage dysplasia (RCUD) (includes refractory anemia (RA))
• Refractory anemia with ringed sideroblasts (RARS)
• Refractory anemia with excess blasts (RAEB-1)
• Refractory anemia with excess blasts (RAEB-2)
• Refractory cytopenia with multilineage dysplasia (RCMD)
• Myelodysplastic syndrome with isolated del(5q) (5q-syndrome)
• Myelodysplastic syndrome (MDS), unclassifiable

3. Patients must have fewer than 20% marrow blasts within 60 days of consent.

4. Patients may have received prior therapy for the treatment of MDS, including but not limited to: growth factor, transfusion support, immunomodulatory (IMID) therapy, DNA hypomethylating therapy, or cytotoxic chemotherapy prior to enrollment.

5. Age 50.0-75.0 years.

6. Karnofsky performance status > 70 or Eastern Cooperative Oncology Group (ECOG) ≤ 1.

7. Patients are eligible if no formal unrelated donor search has been activated prior to date of consent. A formal unrelated donor search begins at the time at which samples are requested from potential National Marrow Donor Program (NMDP) donors. Patients who have started a sibling donor search or who have found a matched sibling donor are eligible.

8. Patients and physicians must be willing to comply with treatment assignment:

1. No intent to proceed with alloHCT using donor sources not specified in this protocol, including human leukocyte antigen (HLA)-mismatched related or unrelated donors (< 6/6 HLA related matched or < 8/8 HLA unrelated matched) or umbilical cord blood unit(s).

2. No intent to use myeloablative conditioning regimens.

3. Intent to proceed with RIC alloHCT if a matched sibling or matched unrelated donor is identified. There is no requirement as to the timing of the transplantation.

9. Patients must be considered to be suitable RIC alloHCT candidates at the time of enrollment based on medical history, physical examination, and available laboratory tests. Specific testing for organ function is not required for eligibility but, if available, these tests should be used to judge eligibility.

10. Signed informed consent

Exclusion Criteria

• Patients with the following will be ineligible for registration onto this study:

1. Therapy-related MDS (defined as the occurrence of MDS due to prior exposure to systemic chemotherapy and/or radiation for malignancy)

2. Current or prior diagnosis of AML

3. Chronic myelomonocytic leukemia or myelodysplastic/myeloproliferative neoplasm (unacceptable MDS subtypes); uncontrolled bacterial, viral or fungal infection (currently taking medication and with progression or no clinical improvement) at time of enrollment.

4. Patients with prior malignancies, except treated non-melanoma skin cancer or treated cervical carcinoma in situ. Cancer treated with curative surgery without chemotherapy/radiation therapy > 5 years previously will be allowed. Cancer treated with curative surgery < 5 years previously will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs.

5. Prior autologous or allogeneic HCT

6. Human Immunodeficiency Virus (HIV) infection

7. Patients of childbearing potential unwilling to use contraceptive techniques

8. Patients with psychosocial conditions that would prevent study compliance

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Blood and Marrow Transplant Clinical Trials Network

NETWORK

Sponsor Role: collaborator

National Marrow Donor Program

OTHER

Sponsor Role: collaborator

Medical College of Wisconsin

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mary Horowitz, MD, MS

Role: STUDY_DIRECTOR

Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin

Locations

City of Hope National Medical Center

Duarte, California, United States

Stanford Hospital and Clinics

Stanford, California, United States

University of Florida College of Medicine

Gainesville, Florida, United States

H. Lee Moffitt Cancer Center

Tampa, Florida, United States

Emory University

Atlanta, Georgia, United States

University of Chicago

Chicago, Illinois, United States

University of Kansas Hospital

Kansas City, Kansas, United States

University of Kentucky

Lexington, Kentucky, United States

University of Maryland Medical Systems - Greenebaum Cancer Center

Baltimore, Maryland, United States

Johns Hopkins

Baltimore, Maryland, United States

Dana Farber Cancer Institute/Brigham & Women's

Boston, Massachusetts, United States

Dana Farber Cancer Institute/Massachusetts General Hospital

Boston, Massachusetts, United States

Karmanos Cancer Institute/BMT

Detroit, Michigan, United States

Mayo Clinic - Rochester

Rochester, Minnesota, United States

Washington University/Barnes Jewish Hospital

St Louis, Missouri, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Mount Sinai Hospital

New York, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

University of North Carolina Hospital at Chapel Hill

Chapel Hill, North Carolina, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Jewish Hospital BMT Program

Cincinnati, Ohio, United States

University Hospitals of Cleveland/ Case Western

Cleveland, Ohio, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Ohio State/Arthur G. James Cancer Hospital

Columbus, Ohio, United States

Oregon Health & Science University

Portland, Oregon, United States

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Baylor College of Medicine/The Methodist Hospital

Houston, Texas, United States

University of Texas/MD Anderson CRC

Houston, Texas, United States

University of Utah Med School

Salt Lake City, Utah, United States

Virginia Commonwealth University MCV Hospitals

Richmond, Virginia, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

West Virginia University Hospital

Morgantown, West Virginia, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

Saber W, Le Rademacher J, Sekeres M, Logan B, Lewis M, Mendizabal A, Leifer E, Appelbaum FR, Horowitz MM, Nakamura R, Cutler CS. Multicenter biologic assignment trial comparing reduced-intensity allogeneic hematopoietic cell transplant to hypomethylating therapy or best supportive care in patients aged 50 to 75 with intermediate-2 and high-risk myelodysplastic syndrome: Blood and Marrow Transplant Clinical Trials Network #1102 study rationale, design, and methods. Biol Blood Marrow Transplant. 2014 Oct;20(10):1566-72. doi: 10.1016/j.bbmt.2014.06.010. Epub 2014 Jun 24.

Reference Type: BACKGROUND

PMID: 24972249 (View on PubMed)

Saber W, Bansal A, Li L, Scott BL, Sangaralingham LR, Thao V, Roth JA, Wright W, Steuten LMG, Pidala JA, Mishra A, Maziarz RT, Westervelt P, McGuirk JP, Cutler C, Nakamura R, Ramsey SD. Cost-Effectiveness of Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation for Older Patients With High-Risk Myelodysplastic Syndrome: Analysis of BMT CTN 1102. JCO Oncol Pract. 2024 Apr;20(4):572-580. doi: 10.1200/OP.23.00413. Epub 2024 Jan 23.

Reference Type: DERIVED

PMID: 38261970 (View on PubMed)

Versluis J, Saber W, Tsai HK, Gibson CJ, Dillon LW, Mishra A, McGuirk J, Maziarz RT, Westervelt P, Hegde P, Mukherjee D, Martens MJ, Logan B, Horowitz M, Hourigan CS, Nakamura R, Cutler C, Lindsley RC; Blood and Marrow Transplant Clinical Trials Network. Allogeneic Hematopoietic Cell Transplantation Improves Outcome in Myelodysplastic Syndrome Across High-Risk Genetic Subgroups: Genetic Analysis of the Blood and Marrow Transplant Clinical Trials Network 1102 Study. J Clin Oncol. 2023 Oct 1;41(28):4497-4510. doi: 10.1200/JCO.23.00866. Epub 2023 Aug 22.

Reference Type: DERIVED

PMID: 37607457 (View on PubMed)

Cusatis R, Martens MJ, Nakamura R, Cutler CS, Saber W, Lee SJ, Logan BR, Shaw BE, Gregory A, D'Souza A, Hamilton BK, Horowitz MM, Flynn KE. Health-related quality of life in reduced-intensity hematopoietic cell transplantation based on donor availability in patients aged 50-75 with advanced myelodysplastic syndrome: BMT CTN 1102. Am J Hematol. 2023 Feb;98(2):229-250. doi: 10.1002/ajh.26768. Epub 2022 Nov 21.

Reference Type: DERIVED

PMID: 36251401 (View on PubMed)

Nakamura R, Saber W, Martens MJ, Ramirez A, Scott B, Oran B, Leifer E, Tamari R, Mishra A, Maziarz RT, McGuirk J, Westervelt P, Vasu S, Patnaik M, Kamble R, Forman SJ, Sekeres MA, Appelbaum F, Mendizabal A, Logan B, Horowitz M, Cutler C. Biologic Assignment Trial of Reduced-Intensity Hematopoietic Cell Transplantation Based on Donor Availability in Patients 50-75 Years of Age With Advanced Myelodysplastic Syndrome. J Clin Oncol. 2021 Oct 20;39(30):3328-3339. doi: 10.1200/JCO.20.03380. Epub 2021 Jun 9.

Reference Type: DERIVED

PMID: 34106753 (View on PubMed)

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Related Links

http://bethematch.org

National Marrow Donor Program

Other Identifiers

2U10HL069294-11

Identifier Type: NIH

Identifier Source: secondary_id

View Link

5U24CA076518

Identifier Type: NIH

Identifier Source: secondary_id

View Link

BMTCTN1102

Identifier Type: -

Identifier Source: org_study_id