Safety and Efficacy of Donor T-lymphocytes Depleted ex Vivo of Host Alloreactive T-cells (ATIR) 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: ATIR
Intervention description: Donor T-lymphocytes depleted ex vivo of host alloreactive T-cells using photodynamic treatment. Single intravenous infusion with 2x10E6 viable T-cells/kg.
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 31.0
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; Photodepletion; Photodynamic treatment; TH9402; Transplant-related mortality; Hematologic malignancy

Summary:

      The purpose of this study is to determine whether ATIR is safe and effective in reducing
      transplant-related mortality and improving overall survival, when infused in patients with a
      hematologic malignancy following a T-cell depleted stem cell graft from a related
      haploidentical donor.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Any of the following hematologic malignancies: a) Acute myeloid leukemia (AML) in
             first remission with high-risk features or in second or higher remission b) Acute
             lymphoblastic leukemia (ALL) in first remission with high-risk features or in second
             or higher remission c) Myelodysplastic syndrome (MDS): transfusion-dependent, or
             intermediate or higher Revised International Prognostic Scoring System (IPSS-R) risk
             group

          -  Eligible for haploidentical stem cell transplantation according to the investigator

        Exclusion Criteria:

          -  Availability of a suitable matched related or unrelated donor following a donor search

          -  In second or higher remission with the previous remission having lasted less than 6
             months

          -  Diffusing capacity for carbon monoxide (DLCO) < 50% predicted

          -  Left ventricular ejection fraction < 50% (evaluated by echocardiogram or multiple
             gated acquisition [MUGA])

          -  Aspartate aminotransferase (AST) > 2.5 x upper limit of normal (ULN)(CTCAE grade 2)

          -  Bilirubin > 1.5 x ULN (CTCAE grade 2)

          -  Creatinine clearance < 50 mL/min (calculated or measured)

          -  Positive test for human immunodeficiency virus (HIV)

          -  Positive pregnancy test (women of childbearing age only)

          -  Prior allogeneic stem cell transplantation using stem cells from a matched sibling
             donor, a matched unrelated donor, a haploidentical donor, or a cord blood donor

          -  Prior autologous stem cell transplantation

          -  Stay at intensive care unit for more than 2 months in the preceding 12 months

          -  Estimated probability of surviving less than 3 months

          -  Known allergy to any of the components of ATIR (e.g., dimethyl sulfoxide)

          -  Any other condition which, in the opinion of the investigator, makes the patient
             ineligible for the study

        Donor inclusion criteria

          -  Haploidentical family donor with 2 to 3 mismatches at the human leukocyte antigen
             (HLA)-A, -B and/or -DR loci of the unshared haplotype

          -  Male or female, age ≥ 16 and ≤ 75 years

          -  Eligible for donation according to the transplantation center

        Donor exclusion criteria

          -  Positive viral test for HIV-1, HIV-2, hepatitis B virus (HBV), hepatitis C virus
             (HCV), Treponema pallidum, human T-lymphotropic virus (HTLV)-1*, HTLV-2*, or West Nile
             virus (WNV)* (if tested) (* at Canadian centers only)

          -  Positive pregnancy test or nursing (women of childbearing age only)