Ground Truth
Inclusion Criteria:Any of the following hematologic malignancies:Acute myeloid leukemia (AML) in first cytomorphological remission (< 5% blasts in the bone marrow) with Disease Risk Index (DRI) intermediate or above, or in second or higher cytomorphological remissionAcute lymphoblastic leukemia (ALL) in first or higher remission (< 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 groupClinical justification of allogeneic stem cell transplantation where a suitable HLA matched sibling or unrelated donor is unavailable in a timely manner.
An unrelated donor search is not required for a patient to be eligible if the clinical situation dictates an urgent transplantation.
Clinical urgency is defined as 6-8 weeks from referral to transplant center or low likelihood of finding a matched unrelated donorAvailability of a related haploidentical donor with ≥ 4/8 but < 7/8, or ≥ 5/10 but < 9/10 matches at the HLA-A, -B, -C, -DRB1, and/or -DQB1 loci, as determined by high resolution human leukocyte antigen (HLA)-typingKarnofsky Performance Status (KPS) ≥ 70%Male or female, age ≥ 18 years and ≤ 70 years.
Patients aged ≥ 65 years must have a Sorror score ≤ 3Availability of a donor aged ≥ 16 years and ≤ 75 years who is eligible according to local requirements and regulationsFor 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 participationGiven written informed consent (patient and donor)Exclusion Criteria:Availability of a suitable HLA-matched sibling or unrelated donor in a donor searchPrior allogeneic hematopoietic stem cell transplantationDiffusing capacity for carbon monoxide (hemoglobin corrected DLCO) < 50% predictedLeft 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)Bilirubin > 1.5 × 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 monthsKnown allergy to any of the components of ATIR101 (e.g., dimethyl sulfoxide)Known hypersensitivity to cyclophosphamide or any of its metabolitesAny contraindication for GVHD prophylaxis with mycophenolate mofetil, cyclosporine A, or tacrolimusKnown presence of HLA antibodies against the non-shared donor haplotypePositive human immunodeficiency virus (HIV) testPositive viral test of the donor for 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
Prediction
Inclusion Criteria:
- Any of the following hematologic malignancies:
- Acute myeloid leukemia (AML) in first cytomorphological remission with Disease Risk Index (DRI) intermediate or above, or in second or higher cytomorphological remission
- Acute lymphoblastic leukemia (ALL) in first or higher remission
- 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.
An unrelated donor search is not required for a patient to be eligible if the clinical situation dictates an urgent transplantation.
Clinical urgency is defined as 6-8 weeks from referral to transplant center or low likelihood of finding a matched unrelated donor
- Availability of a related haploidentical donor with ≥ 4/8 but < 8/8, or ≥ 5/10 but < 10/10 matches at the HLA-A, -B, -C, -DRB1, and/or -DQB1 loci, 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
- Availability of a donor aged ≥ 16 years and ≤ 75 years who is eligible according to local requirements and regulations
- For females of childbearing potential who are sexually active and males who have sexual contact with a female of childbearing potential: use of reliable methods of contraception during study participation
- Given written informed consent (patient and donor)
Exclusion Criteria:
- Availability of a suitable fully matched related or unrelated donor in a donor search
- Prior allogeneic hematopoietic stem cell transplantation
- Diffusing capacity for carbon monoxide (DLCO) < 50% predicted
- Left ventricular ejection fraction < 50% (evaluated by echocardiogram or MUGA)
- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2.5 × upper limit of normal (CTCAE grade 2)
- Bilirubin > 1.5 × 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
- Known presence of HLA antibodies against the non-shared donor haplotype
- Positive human immunodeficiency virus (HIV) test
- Positive CMV test of the patient and negative cytomegalovirus (CMV) test of the donor
- Positive viral test of the donor for 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