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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

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ClinicalTrials.gov Identifier: NCT02500550
Recruitment Status : Completed
First Posted : July 16, 2015
Last Update Posted : April 8, 2020
Sponsor:
Information provided by (Responsible Party):
Kiadis Pharma

Tracking Information
First Submitted Date  ICMJE July 14, 2015
First Posted Date  ICMJE July 16, 2015
Last Update Posted Date April 8, 2020
Actual Study Start Date  ICMJE October 9, 2015
Actual Primary Completion Date July 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 14, 2015)
Incidence of acute graft versus host disease (GvHD) grade III/IV [ Time Frame: 180 days post HSCT ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 14, 2015)
  • Incidence of acute and chronic GvHD [ Time Frame: 12 months post HSCT ]
  • Severity of acute and chronic GvHD [ Time Frame: 12 months post HSCT ]
  • Time to T-cell reconstitution, [ Time Frame: 12 months post HSCT ]
    Defined as the time to CD3+ in peripheral blood higher than 0.2×10E9/L (at two consecutive measurements; time to first measurement)
  • Incidence of viral, fungal, and bacterial infections [ Time Frame: 12 months post HSCT ]
  • Severity of viral, fungal, and bacterial infections [ Time Frame: 12 months post HSCT ]
  • Transplant-related mortality (TRM) [ Time Frame: 12 months post HSCT ]
    Defined as death due to causes other than disease relapse or progression, or other causes which are unrelated to the transplantation procedure (e.g. accident, suicide)
  • Relapse-related mortality (RRM) [ Time Frame: 12 months post HSCT ]
    Defined as death due to disease relapse or disease progression
  • Overall survival (OS) [ Time Frame: 12 months post HSCT ]
    Defined as the time from HSCT until death from any cause
  • Progression-free survival (PFS) [ Time Frame: 12 months post HSCT ]
    Defined as the time from HSCT until relapse, disease progression, or death, whichever occurs first
  • GvHD-free, relapse-free survival (GRFS) [ Time Frame: 12 months post HSCT ]
    Defined as the time until acute GvHD grade III/IV, chronic GvHD requiring systemic treatment, relapse, or death, whichever occurs first
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE An Exploratory, Open-label, Multicenter Study to Evaluate the Safety and Efficacy of a Two-dose Regimen of ATIR101, a T-lymphocyte Enriched Leukocyte Preparation Depleted ex Vivo of Host Alloreactive T-cells (Using Photodynamic Treatment), in Patients With a Hematologic Malignancy, Who Received a CD34-selected Hematopoietic Stem Cell Transplantation From a Haploidentical Donor
Brief 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Acute Myeloid Leukemia
  • Acute Lymphoblastic Leukemia
  • Myelodysplastic Syndrome
Intervention  ICMJE
  • Biological: ATIR101
    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).
  • Procedure: Haploidentical hematopoietic stem cell transplantation (HSCT)

    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:

    • Totol Body Irradiation (TBI) regime
    • Non-TBI regime

    (See below for details)

  • Procedure: TBI regime
    • 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.
  • Procedure: Non-TBI regime
    • 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.
Study Arms  ICMJE Experimental: ATIR101
Interventions:
  • Biological: ATIR101
  • Procedure: Haploidentical hematopoietic stem cell transplantation (HSCT)
  • Procedure: TBI regime
  • Procedure: Non-TBI regime
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 14, 2015)
15
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 2019
Actual Primary Completion Date July 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Any of the following hematologic malignancies:

    • Acute myeloid leukemia (AML) in first remission with high-risk features or in second or higher remission
    • Acute lymphoblastic leukemia (ALL) in first remission with high-risk features or in second or higher remission
    • Myelodysplastic syndrome (MDS): transfusion-dependent, or intermediate or higher IPSS-R risk group
  • Karnofsky performance status ≥ 70%
  • Eligible for haploidentical stem cell transplantation according to the investigator
  • Male or female, age ≥ 18 years and ≤ 65 years

Exclusion Criteria:

  • Availability of a fully matched related or unrelated donor following a donor search
  • Diffusing capacity for carbon monoxide (DLCO) < 50% predicted
  • Left ventricular ejection fraction < 50% (evaluated by echocardiogram or MUGA)
  • AST > 2.5 x ULN (CTCAE grade 2)
  • Bilirubin > 1.5 x ULN (CTCAE grade 2)
  • Creatinine clearance < 50 mL/min (calculated or measured)
  • Positive HIV test
  • Positive pregnancy test (women of childbearing age only)
  • Prior allogeneic HSCT
  • Estimated probability of surviving less than 3 months
  • Known allergy to any of the components of ATIR101 (e.g., dimethyl sulfoxide)
  • Known presence of HLA antibodies against the non-shared donor haplotype
  • Any other condition which, in the opinion of the investigator, makes the patient ineligible for the study

Inclusion Criteria Donor:

  • Haploidentical family donor with 2 to 3 mismatches at the HLA-A, -B and/or -DR loci of the unshared haplotype
  • Male or female, age ≥ 16 and ≤ 75 years (If applicable, local legal requirements for donors under the age of 18 will be followed)
  • Eligible for donations of human blood and blood components according to local requirements and regulations
  • Eligible for donation according to the transplantation center

Exclusion Criteria Donor:

  • Positive pregnancy test or nursing (women of childbearing age only)
  • Positive viral test for HIV-1, HIV-2, HBV, HCV, Treponema pallidum, HTLV 1 (if tested), HTLV-2 (if tested), or WNV (if tested)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   Croatia,   Germany,   Portugal,   United Kingdom
Removed Location Countries Israel,   United States
 
Administrative Information
NCT Number  ICMJE NCT02500550
Other Study ID Numbers  ICMJE CR-AIR-008
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Kiadis Pharma
Study Sponsor  ICMJE Kiadis Pharma
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Denis Claude Roy, Prof MD Maisonneuve-Rosemont Hospital (Montreal, Canada)
Principal Investigator: Stephan Mielke, Prof MD Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital (Stockholm, Sweden)
PRS Account Kiadis Pharma
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP