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

An Exploratory, Open-label, Multicenter Study to Evaluate the Safety and Efficacy of ATIR, Donor T-lymphocytes Depleted ex Vivo of Host Alloreactive T-cells, in Patients With a Hematologic Malignancy, Who Received a CD34-selected Hematopoietic Stem Cell Transplantation From a Haploidentical Donor

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.

Study CR-AIR-007 is an exploratory, open-label, multicenter study. After signing informed consent, patients will receive a hematopoietic stem cell transplantation (HSCT) from a related, haploidentical donor, followed by infusion with ATIR between 28 and 32 days after the HSCT (or later if required by the patient's medical condition). Patients will receive ATIR as a single infusion at a dose of 2x10E6 viable T-cells/kg. All patients treated with ATIR will be followed up until 12 months after the HSCT. Assessments will be performed at weekly visits from the day of ATIR infusion until 8 weeks after ATIR infusion, at monthly visits from 3 until 6 months after the HSCT, every 2 months from 6 until 12 months after the HSCT, and every 6 months from 12 until 24 months after the HSCT.

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)