Safety and Efficacy of ATIR101 as Adjunctive Treatment to Blood Stem Cell Transplantation From a Haploidentical Family Donor Compared to Post-transplant Cyclophosphamide in Patients With Blood Cancer (HATCY)

This is an interventional prevention trial for Acute Myeloid Leukemia focused on measuring Haploidentical stem cell transplantation, Graft-versus-host disease, Immune reconstitution, Alloreactive T-cells, Photodynamic treatment, Hematologic malignancy, Transplant-related mortality, Overall survival, GRFS, GVHD Read More

Inclusion Criteria:

• Any of the following hematologic malignancies:

  • Acute myeloid leukemia (AML) in first cytomorphological remission (with < 5% blasts in the bone marrow) with Disease Risk Index (DRI) intermediate or above, or in second or higher cytomorphological remission (with < 5% blasts in the bone marrow)
  • Acute lymphoblastic leukemia (ALL) in first or higher remission (with < 5% blasts in the bone marrow)
  • Myelodysplastic syndrome (MDS): transfusion-dependent (requiring at least one transfusion per month), or intermediate or higher Revised International Prognostic Scoring System (IPSS-R) risk group
• Clinical justification of allogeneic stem cell transplantation where a suitable HLA matched sibling or unrelated donor is unavailable in a timely manner
• Availability of a related haploidentical donor with one fully shared haplotype and 2 to 4 mismatches at the HLA-A, -B, -C, and -DRB1 loci of the unshared haplotype, as determined by high resolution human leukocyte antigen (HLA)-typing
• Karnofsky Performance Status (KPS) ≥ 70%
• Male or female, age ≥ 18 years and ≤ 70 years. Patients aged ≥ 65 years must have a Sorror score ≤ 3
• Patient weight ≥ 25 kg and ≤ 130 kg
• Availability of a donor aged ≥ 16 years and ≤ 75 years who is eligible according to local requirements and regulations. Donors aged < 16 years are allowed if they are the only option for an HSCT, if they are permitted by local regulations, and if the IRB/IEC approves participation in the study.
• For females of childbearing potential who are sexually active and males who have sexual contact with a female of childbearing potential: willingness to use of reliable methods of contraception (oral contraceptives, intrauterine device, hormone implants, contraceptive injection or abstinence) during study participation
• Given written informed consent (patient and donor)

Exclusion Criteria:

• Diagnosis of chronic myelomonocytic leukemia (CMML)
• Availability of a suitable HLA-matched sibling or unrelated donor in a donor search
• Prior allogeneic hematopoietic stem cell transplantation
• Diffusing capacity for carbon monoxide (hemoglobin corrected DLCO) < 50% predicted
• Left ventricular ejection fraction < 45% (evaluated by echocardiogram or MUGA scan)
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2.5 × upper limit of normal (CTCAE grade 2)
• Creatinine clearance < 50 ml/min (calculated or measured)
• Positive pregnancy test or breastfeeding of patient or donor (women of childbearing age only)
• Estimated probability of surviving less than 3 months
• Known allergy to any of the components of ATIR101 (e.g., dimethyl sulfoxide)
• Known hypersensitivity to cyclophosphamide or any of its metabolites
• Any contraindication for GVHD prophylaxis with mycophenolate mofetil, cyclosporine A, or tacrolimus
• Known presence of HLA antibodies against the non-shared donor haplotype
• Positive viral test of the patient or donor for human immunodeficiency virus (HIV)-1, HIV-2, hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum, human T-lymphotropic virus (HTLV)-1 (if tested), HTLV-2 (if tested), West Nile virus (WNV; if tested), or Zika virus (if tested)
• Any other condition that, in the opinion of the investigator, makes the patient or donor ineligible for the study