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
Condition: Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndrome
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes
Intervention: ATIR101; Cyclophosphamide; T-cell depleted HSCT from a related, haploidentical donor; T-cell replete HSCT from a related, haploidentical donor
Intervention description: ATIR101 is a T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells using photodynamic treatment; single dose of 2×10E6 viable T-cells/kg body weight between 28 and 32 days after the HSCT (intravenous infusion); High dose post-transplant cyclophosphamide 50 mg/kg/day at 3 and 4/5 days after the HSCT (powder for intravenous infusion); T-cell depleted graft prepared from peripheral blood stem cells using the CD34+ cell selection method; infused after a total body irradiation (TBI) or non-TBI conditioning regimen; T-cell replete (full, non-manipulated) graft prepared from either bone marrow or peripheral blood stem cells; infused after a total body irradiation (TBI) or non-TBI conditioning regimen
Intervention MeSH terms: Cyclophosphamide
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 63.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 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; Overall survival; GRFS; GVHD

Summary:

      The primary objective of this study is to compare safety and efficacy of a haploidentical
      T-cell depleted HSCT and adjunctive treatment with ATIR101 versus a haploidentical T cell
      replete HSCT with post-transplant administration of high dose cyclophosphamide (PTCy) in
      patients with a hematologic malignancy. An additional objective of the study is to compare
      the effect of the two treatments on quality of life.
    

Eligibility criteria:

        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