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Allo vs Hypomethylating/Best Supportive Care in MDS (BMT CTN 1102)

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ClinicalTrials.gov Identifier: NCT02016781
Recruitment Status : Active, not recruiting
First Posted : December 20, 2013
Last Update Posted : October 12, 2020
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
National Cancer Institute (NCI)
Blood and Marrow Transplant Clinical Trials Network
National Marrow Donor Program
Information provided by (Responsible Party):
Medical College of Wisconsin

Tracking Information
First Submitted Date  ICMJE December 16, 2013
First Posted Date  ICMJE December 20, 2013
Last Update Posted Date October 12, 2020
Actual Study Start Date  ICMJE February 28, 2014
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 2, 2018)
Overall survival [ Time Frame: 3 years ]
Overall survival is calculated for all patients from date of patient consent until death from any cause. Observation is censored at the date of last follow-up for patients last known to be alive.
Original Primary Outcome Measures  ICMJE
 (submitted: December 19, 2013)
Overall survival probabilities [ Time Frame: 3 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 16, 2019)
  • Leukemia-free survival (LFS) [ Time Frame: 3 years ]
    LFS is defined as the time from the date of patient consent to the date of progression to AML or death from any cause, whichever comes first. Observation is censored at the date of last follow-up for patients known to be alive without leukemia. Progression to AML is defined as > 20% leukemic blasts in bone marrow or in the peripheral blood.
  • Number of participants on HCT arm with disease relapse [ Time Frame: 3 years ]
    Disease relapse for patients with MDS is defined as: Satisfying criteria for evolution into acute leukemia; or reappearance of pre-transplant morphologic abnormalities, detected in bone marrow specimens; or reappearance of pre-transplant cytogenetic abnormality in at least one metaphase on each of two separate consecutive examinations at least one month apart, regardless of the number of metaphases analyzed; or institution of any therapy to treat relapsed disease (institution of any therapy not meant for maintenance or prevention), including withdrawal of immunosuppressive therapy or DLI.
  • Cost-Effectiveness Analysis (CEA) [ Time Frame: 3 years ]
    The primary endpoint for the CEA will be the cost per quality-adjusted life year (QALY) from the third party payer perspective with two time horizons: (1) within trial (at 3 years post-enrollment), and (2) lifetime using simulating modeling. The secondary endpoint for the CEA is the cost per QALY from the societal perspective, a broader measure that captures health insurer direct medical care costs and patient out-of-pocket direct medical and direct non-medical costs. Patient productivity costs (captured as part of QALY calculations) will be reported separately.
  • Quality of Life (QOL) - (Functional Assessment of Cancer Therapy-Bone Marrow Transplant) FACT-BMT [ Time Frame: 3 years ]
    QOL will be compared between the 2 arms using the FACT-BMT survey.
  • Quality of Life (QOL) - Medical Outcomes Study Short Form (MOS SF-36) [ Time Frame: 3 years ]
    QOL will be compared between the 2 arms using the MOS SF-36 survey.
  • Quality of Life (QOL) - EQ-5D [ Time Frame: 3 years ]
    QOL will be compared between the 2 arms using the EQ-5D survey.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 19, 2013)
  • Leukemia-free survival (LFS) [ Time Frame: 3 years ]
  • QOL measures [ Time Frame: 3 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Allo vs Hypomethylating/Best Supportive Care in MDS (BMT CTN 1102)
Official Title  ICMJE 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 (BMT CTN #1102)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Two arms will enroll and have data collected on them simultaneously.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE MDS
Intervention  ICMJE
  • Procedure: 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.
    Other Name: RIC alloHCT
  • Procedure: Hypomethylating Therapy / Best Supportive Care
    The specific non-transplant treatment regimen will be at the discretion of the treating physician.
    Other Name: Non-transplant
Study Arms  ICMJE
  • Active Comparator: Transplant
    Reduced intensity conditioning allogeneic hematopoietic cell transplantation (RIC-alloHCT)
    Intervention: Procedure: Allogeneic Hematopoietic Cell Transplant
  • Active Comparator: Hypomethylating Therapy / Best Supportive Care
    The specific non-transplant treatment regimen will be at the discretion of the treating physician.
    Intervention: Procedure: Hypomethylating Therapy / Best Supportive Care
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 5, 2020)
384
Original Estimated Enrollment  ICMJE
 (submitted: December 19, 2013)
400
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02016781
Other Study ID Numbers  ICMJE BMTCTN1102
2U10HL069294-11 ( U.S. NIH Grant/Contract )
5U24CA076518 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Supporting Materials: 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/
Responsible Party Medical College of Wisconsin
Study Sponsor  ICMJE Medical College of Wisconsin
Collaborators  ICMJE
  • National Heart, Lung, and Blood Institute (NHLBI)
  • National Cancer Institute (NCI)
  • Blood and Marrow Transplant Clinical Trials Network
  • National Marrow Donor Program
Investigators  ICMJE
Study Director: Mary Horowitz, MD, MS Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin
PRS Account Medical College of Wisconsin
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP