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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome

Intervention / Treatment
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* Biological: ATIR


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ATIR<br> | Biological: ATIR<br>* Donor T-lymphocytes depleted ex vivo of host alloreactive T-cells using photodynamic treatment. Single intravenous infusion with 2x10E6 viable T-cells/kg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transplant-related Mortality (TRM) | TRM is 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). The TRM rate is displayed as a function of time using the Kaplan-Meier method. The TRM rate at 6 months post HSCT is estimated from this analysis. | At 6 months post HSCT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune Reconstitution | Immunophenotyping on peripheral blood samples by means of flow cytometry assessment of immune subsets was done if the absolute lymphocyte count was higher than 0.1×10E9/l | Up to 24 months post HSCT | 
| Relapse-related Mortality (RRM) | Defined as death due to disease relapse or disease progression. The Kaplan-Meier analysis resulted in estimates and 95% confidence intervals (CI)s. | 6, 12 and 24 months post HSCT | 
| Overall Survival (OS) | Defined as the time from HSCT until death from any cause. The Kaplan-Meier analysis resulted in estimates and 95% CIs. | 6, 12 and 24 months post HSCT | 
| Progression-free Survival (PFS) | Defined as the time from HSCT until relapse, disease progression, or death, whichever occurs first. The Kaplan-Meier analysis resulted in estimates and 95% CIs. | 6, 12 and 24 months post HSCT | 
| Number of Participants With Viral, Fungal, and Bacterial Infections. |  | Up to 24 months post HSCT | 
| Number of Participants With Graft Versus Host Disease (GVHD) |  | Up to 24 months post HSCT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Haploidentical stem cell transplantation, Graft-versus-host disease, Immune reconstitution, Alloreactive T-cells, Photodepletion, Photodynamic treatment, TH9402, Transplant-related mortality, Hematologic malignancy