The Rapid Study: Randomized Phase II Study To Expedite Allogeneic Transplant With Immediate Haploidentical Plus Unrelated Cord Donor Search Versus Matched Unrelated Donor Search For AML And High-Risk MDS Patients
Condition: Acute Myeloid Leukemia (AML); Myelodysplastic Syndrome (MDS)
MeSH terms: Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Myelodysplastic Syndromes
Intervention: Haplo-Cord Transplant; Matched Unrelated Donor Transplant
Intervention description: For conditioning regimens, haplo-identical grafts will be selected by the Miltenyi Device
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Acute Myeloid Leukemia (AML); High-Risk Myelodysplastic Syndrome (MDS); hematopoietic cell transplantation; haplo-cord search; matched unrelated donor search

Summary:

      The study seeks to compare time from formal search to hematopoietic cell transplantation
      (HCT) for patients 18 years and older, randomized between haplo-cord search and matched
      unrelated donor (MUD) search for patients with acute myeloid leukemia (AML) and high-risk
      myelodysplastic syndrome (MDS)
    

Eligibility criteria:

        Inclusion Criteria for Search Phase:

          1. Diagnosis of acute myeloid leukemia (AML) or high or very high-risk MDS by
             international prognostic scoring system revised for whom transplant is recommended

          2. 18 years of age or older

          3. Subject is likely to be considered for allogeneic transplant in the opinion of the
             transplant physician (based on age of patient, health, cytogenetics, and/or molecular
             characteristics).

          4. Karnofsky Performance Status (KPS) >/= 70% at time of enrollment. An exception will be
             made for those with lower KPS at enrollment with an acute worsening that is likely to
             resolve in the treating physicians judgment (e.g., reversible infection,trauma,
             medication reaction, etc)

          5. Ability to understand and the willingness to sign a written informed consent document
             for the Search Phase.

          6. Patient willing to consider HCT

          7. A preliminary search has identified:

               1. An appropriate minimum 4/6 matched umbilical cord unit at intermediate resolution
                  at HLA-A and B, and high resolution at HLA-DRB with a cell dose above 1 x 10(7)
                  TNC/kg for a single umbilical cord blood (UCB) transplant AND

               2. At least one potential 8/8 HLA-matched (HLA-A, -B, -C, and -DRB1) unrelated donor
                  with a probability of 70% AND

               3. Availability of a potential related haploidentical donor.

        Exclusion Criteria for Search Phase:

          1. Prior formal search was instituted

          2. Diagnosis of acute promyelocytic leukemia (APL)

          3. Known HLA matched related donor without contraindications to donate

          4. Life expectancy severely limited by concomitant illness or uncontrolled infection

        Inclusion Criteria for Transplant Phase

          1. High-risk AML for which transplant is recommend based on cytogenetic, molecular and
             morphologic features. Patients must meet institutional standards for disease control
             prior to transplant.

          2. For MDS. IPSS-revised criteria of high or very high at diagnosis.

          3. Subject meets institutional criteria for transplant and has acceptable organ and
             marrow function as defined below:

               1. Serum bilirubin < 2.0mg/dL unless Gilberts disease

               2. Creatinine Clearance > 45 mL/min.1.73m2 as estimated by modified MDRD equation

               3. Left ventricular function 40% or greater

               4. DLCO corrected for hemoglobin >50%

               5. KPS 70% or greater

          4. An adequate graft for the defined donor type

               1. Haplo-cord requires a haploidentical adult donor of 14 years of age and at least
                  50 kg, and a cord blood unit with at least 1.0 x 10(7) TNC/kg and a match of at
                  least 4/6 by intermediate resolution for HLA-A and B and high resolution at DRB1.
                  Donor provides standard of care consent for harvest following institutional
                  policy. Any donor samples or donor research data would be obtained on separate
                  donor research protocol.

               2. For MUD requires a 7/8 or 8/8 HLA matched unrelated donor with high resolution
                  matching at HLA-A, -B, -C, and DRB1. DP matching or DP permissive should be
                  achieved when possible using T-cell epitope strategy.

          5. Written informed consent for the transplant phase

        Exclusion Criteria for Transplant Phase

          1. Life expectancy severely limited by concomitant illness or uncontrolled infection

          2. HIV-positive