Safety and Efficacy of Two Doses of ATIR101, a T-lymphocyte Enriched Leukocyte Preparation Depleted of Host Alloreactive T-cells, in Patients With a Hematologic Malignancy Who Received a Hematopoietic Stem Cell Transplantation From a Haploidentical Donor
Condition: Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndrome
MeSH terms: Leukemia; Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hematologic Neoplasms; Myelodysplastic Syndromes
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to determine whether a repeat dose administration of ATIR101 is
      safe and effective when infused in patients with a hematologic malignancy following a T-cell
      depleted stem cell graft from a related haploidentical donor. All patients are planned to
      receive two ATIR101 doses of 2×10E6 viable T-cells/kg, unless the second dose is reduced or
      halted for safety reasons.
    

Detailed description: 
      Study CR-AIR-008 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 a first ATIR101 infusion at a dose of 2×10E6
      viable T-cells/kg between 28 and 32 days after the HSCT. Patients will receive a second
      ATIR101 infusion at a dose of 2×10E6 viable T-cells/kg between 70 and 74 days after the HSCT.
      To evaluate safety of the second dose administration, the first 6 patients treated will be
      evaluated for the occurrence of dose limiting toxicity (DLT), defined as acute GvHD grade
      III/IV within 120 days post HSCT (or within 42 days after the second ATIR101 infusion in case
      of prior dose delays). If within the first 6 patients no DLT is observed, treatment of the
      remaining 9 patients will continue with two ATIR101 doses of 2×10E6 viable T cells/kg. If
      within the first 6 patients at least 2 patients show DLT, the second ATIR101 infusion will be
      adjusted to a dose of 1×10E6 viable T cells/kg. If in one of the next 3 patients treated at
      this lower dose again DLT is observed, the second ATIR101 infusion will be halted and the
      remaining patients will be given only a single dose of ATIR101.

      All patients treated with ATIR101 will be followed up until 12 months after the HSCT.
      Assessments will be performed at weekly visits from the day of the first ATIR101 infusion
      (Week 4) until 6 weeks after the second ATIR101 infusion (Week 16), at monthly visits from 4
      until 6 months after the HSCT, and every 3 months from 6 until 12 months after the HSCT.
    

Intervention name(s): ATIR101; Haploidentical hematopoietic stem cell transplantation (HSCT); TBI regime; Non-TBI regime
Intervention type(s): Biological; Procedure; Procedure; Procedure
Intervention description(s): T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons).; CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended:
Total Body Irradiation (TBI) regime
Non-TBI regime
(See below for details); Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions)
Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3
Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.; Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4
Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7
Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1
ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Haploidentical stem cell transplantation; Graft versus host disease; Immune reconstitution; Alloreactive T-cells; Photodynamic treatment; Hematologic malignancy; Transplant-related mortality