Safety and Efficacy of Two Doses of ATIR101, a T-lymphocyte Enriched Leukocyte Preparation Depleted of Host Alloreactive T-cells, in Patients With a Hematologic Malignancy Who Received a Hematopoietic Stem Cell Transplantation From a Haploidentical Donor
Condition: Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndrome
MeSH terms: Leukemia; Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hematologic Neoplasms; Myelodysplastic Syndromes
Intervention: ATIR101; Haploidentical hematopoietic stem cell transplantation (HSCT); TBI regime; Non-TBI regime
Intervention description: T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons).; CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended:
Total Body Irradiation (TBI) regime
Non-TBI regime
(See below for details); Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions)
Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3
Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.; Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4
Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1
ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Haploidentical stem cell transplantation; Graft versus host disease; Immune reconstitution; Alloreactive T-cells; Photodynamic treatment; Hematologic malignancy; Transplant-related mortality

Summary:

      The purpose of this study is to determine whether a repeat dose administration of ATIR101 is
      safe and effective when infused in patients with a hematologic malignancy following a T-cell
      depleted stem cell graft from a related haploidentical donor. All patients are planned to
      receive two ATIR101 doses of 2×10E6 viable T-cells/kg, unless the second dose is reduced or
      halted for safety reasons.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Any of the following hematologic malignancies:

               -  Acute myeloid leukemia (AML) in first remission with high-risk features or in
                  second or higher remission

               -  Acute lymphoblastic leukemia (ALL) in first remission with high-risk features or
                  in second or higher remission

               -  Myelodysplastic syndrome (MDS): transfusion-dependent, or intermediate or higher
                  IPSS-R risk group

          -  Karnofsky performance status ≥ 70%

          -  Eligible for haploidentical stem cell transplantation according to the investigator

          -  Male or female, age ≥ 18 years and ≤ 65 years

        Exclusion Criteria:

          -  Availability of a fully matched related or unrelated donor following a donor search

          -  Diffusing capacity for carbon monoxide (DLCO) < 50% predicted

          -  Left ventricular ejection fraction < 50% (evaluated by echocardiogram or MUGA)

          -  AST > 2.5 x ULN (CTCAE grade 2)

          -  Bilirubin > 1.5 x ULN (CTCAE grade 2)

          -  Creatinine clearance < 50 mL/min (calculated or measured)

          -  Positive HIV test

          -  Positive pregnancy test (women of childbearing age only)

          -  Prior allogeneic HSCT

          -  Estimated probability of surviving less than 3 months

          -  Known allergy to any of the components of ATIR101 (e.g., dimethyl sulfoxide)

          -  Known presence of HLA antibodies against the non-shared donor haplotype

          -  Any other condition which, in the opinion of the investigator, makes the patient
             ineligible for the study

        Inclusion Criteria Donor:

          -  Haploidentical family donor with 2 to 3 mismatches at the HLA-A, -B and/or -DR loci of
             the unshared haplotype

          -  Male or female, age ≥ 16 and ≤ 75 years (If applicable, local legal requirements for
             donors under the age of 18 will be followed)

          -  Eligible for donations of human blood and blood components according to local
             requirements and regulations

          -  Eligible for donation according to the transplantation center

        Exclusion Criteria Donor:

          -  Positive pregnancy test or nursing (women of childbearing age only)

          -  Positive viral test for HIV-1, HIV-2, HBV, HCV, Treponema pallidum, HTLV 1 (if
             tested), HTLV-2 (if tested), or WNV (if tested)