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.
Study CR-AIR-009 is a Phase III randomized controlled multicenter open-label study comparing
two parallel groups. After signing informed consent, a total of 250 patients will be
randomized in a 1:1 fashion to receive either a T-cell depleted hematopoietic stem cell
transplantation (HSCT; CD34 selection) from a related, haploidentical donor, followed by
ATIR101 infusion, or a T-cell replete HSCT, followed by a high dose of post-transplant
cyclophosphamide (PTCy).
Randomization will use minimization to balance treatment groups with respect to underlying
disease (AML, ALL, or MDS), Disease Risk Index (DRI; intermediate risk, high risk, or very
high risk) and center. A stochastic treatment allocation procedure will be used so that the
treatment assignment is random for all patients entered in the study.
Patients randomized in the ATIR101 group will receive a single ATIR101 dose of 2×10E6 viable
T-cells/kg between 28 and 32 days after the HSCT. Patients randomized in the PTCy group will
receive cyclophosphamide 50 mg/kg/day at 3 and 4/5 days after the HSCT. All patients will be
followed up for at least 24 months post HSCT.
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
