Clinical Trials /

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

NCT02016781

Description:

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.

Related Conditions:
  • Myelodysplastic Syndrome with Isolated del(5q)
  • Myelodysplastic Syndrome, Unclassifiable
  • Refractory Anemia
  • Refractory Anemia with Excess Blasts
  • Refractory Cytopenia with Multilineage Dysplasia
  • Refractory Cytopenia with Unilineage Dysplasia
  • Refractory anemia with ring sideroblasts
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Allo vs Hypomethylating/Best Supportive Care in MDS (BMT CTN 1102)
  • 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 (BMT CTN #1102)

Clinical Trial IDs

  • ORG STUDY ID: BMTCTN1102
  • SECONDARY ID: 2U10HL069294-11
  • SECONDARY ID: 5U24CA076518
  • NCT ID: NCT02016781

Conditions

  • MDS

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
TransplantActive ComparatorReduced intensity conditioning allogeneic hematopoietic cell transplantation (RIC-alloHCT)
    Hypomethylating Therapy / Best Supportive CareActive ComparatorThe specific non-transplant treatment regimen will be at the discretion of the treating physician.

      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
            
      Maximum Eligible Age:75 Years
      Minimum Eligible Age:50 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Overall survival
      Time Frame:3 years
      Safety Issue:
      Description: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.

      Secondary Outcome Measures

      Measure:Leukemia-free survival (LFS)
      Time Frame:3 years
      Safety Issue:
      Description: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.
      Measure:Number of participants on HCT arm with disease relapse
      Time Frame:3 years
      Safety Issue:
      Description: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.
      Measure:Cost-Effectiveness Analysis (CEA)
      Time Frame:3 years
      Safety Issue:
      Description: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.
      Measure:QOL using the EQ-5D
      Time Frame:3 years
      Safety Issue:
      Description:Patient reported state of health will be compared between the 2 arms.
      Measure:QOL using the FACT-BMT
      Time Frame:3 years
      Safety Issue:
      Description:Patient reported well-being will be compared between the 2 arms.
      Measure:QOL using the MOS SF-36
      Time Frame:3 years
      Safety Issue:
      Description:Patient reported health status will be compared between the 2 arms.

      Details

      Phase:Phase 2
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:Medical College of Wisconsin

      Trial Keywords

      • Myelodysplastic Syndrome

      Last Updated