Clinical trial NCT02016781: Allo vs Hypomethylating/Best Supportive Care in MDS (BMTCTN1102)
Official title: A Multi-Center Biologic Assignment Trial Comparing Allogeneic Hematopoietic Cell Transplant to Hypomethylating Therapy or Best Supportive Care in Patients w/Intermediate-2 & High Risk Myelodysplastic Syndrome (BMTCTN1102)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: MDS
Keywords: Myelodysplastic Syndrome
Lead sponsor: Medical College of Wisconsin
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: National Cancer Institute (NCI)
name: Blood and Marrow Transplant Clinical Trials Network
name: National Marrow Donor Program
First posted: 2013-12-20
Enrollment: 384
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two arms will enroll and have data collected on them simultaneously.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Participants With Overall Survival (OS)
timeFrame: 3 years
Secondary outcomes:
measure: Percentage of Participants With Leukemia-free Survival (LFS)
timeFrame: 3 years
measure: Quality of Life (QOL) - Functional Assessment of Cancer Therapy-General (FACT-G)
timeFrame: 3 years
measure: Quality of Life (QOL) - Medical Outcomes Study Short Form (MOS SF-36)
timeFrame: 3 years
measure: Quality of Life (QOL) - EQ-5D
timeFrame: 3 years
measure: Percentage of Participants With Overall Survival (OS) in As-treated Population
timeFrame: 3 years
measure: Percentage of Participants With Leukemia-free Survival (LFS) in As-treated Population
timeFrame: 3 years
measure: Percentage of Participants on HCT Arm With Overall Survival (OS)
timeFrame: 27 months post-transplant
measure: Percentage of Participants on HCT Arm With Disease Relapse
timeFrame: 27 months post-transplant
measure: Percentage of Participants on HCT Arm With Disease-free Survival (DFS)
timeFrame: 27 months post-transplant
measure: Percentage of Participants on HCT Arm With Treatment-related Mortality
timeFrame: 27 months post-transplant
measure: Percentage of Participants on HCT Arm With Grade II-IV Acute GVHD (aGVHD)
timeFrame: 27 months post-transplant
measure: Percentage of Participants on HCT Arm With Grade III-IV Acute GVHD
timeFrame: 27 months post-transplant
measure: Percentage of Participants on HCT Arm With Chronic GVHD
timeFrame: 27 months post-transplant
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Stanford
country: United States
facility: Stanford Hospital and Clinics
state: California
city: Gainesville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Hospital
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland Medical Systems - Greenebaum Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute/Brigham & Women's
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute/Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute/BMT
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University/Barnes Jewish Hospital
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Hospital at Chapel Hill
state: North Carolina
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cincinnati
country: United States
facility: Jewish Hospital BMT Program
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals of Cleveland/ Case Western
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State/Arthur G. James Cancer Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine/The Methodist Hospital
state: Texas
city: Houston
country: United States
facility: University of Texas/MD Anderson CRC
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Med School
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University MCV Hospitals
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Hospital
state: West Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin
name: Mary Horowitz, MD, MS
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.