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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

Primary Purpose

Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ATIR
Sponsored by
Kiadis Pharma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Acute Myeloid Leukemia focused on measuring Haploidentical stem cell transplantation, Graft-versus-host disease, Immune reconstitution, Alloreactive T-cells, Photodepletion, Photodynamic treatment, TH9402, Transplant-related mortality, Hematologic malignancy

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Algemeen Ziekenhuis Sint-Jan
  • Université Libre de Bruxelles - Institute Jules Bordet
  • Universitair Ziekenhuis Gasthuisberg
  • Juravinski Hospital and Cancer Centre
  • Princess Margaret Hospital
  • Maisonneuve-Rosemont Hospital
  • Universitätsklinikum Würzburg
  • Hammersmith Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ATIR

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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.
Overall Survival (OS)
Defined as the time from HSCT until death from any cause. The Kaplan-Meier analysis resulted in estimates and 95% CIs.
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.
Number of Participants With Viral, Fungal, and Bacterial Infections.
Number of Participants With Graft Versus Host Disease (GVHD)

Full Information

First Posted
February 14, 2013
Last Updated
March 17, 2021
Sponsor
Kiadis Pharma
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1. Study Identification

Unique Protocol Identification Number
NCT01794299
Brief Title
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
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
March 2013 (Actual)
Primary Completion Date
June 2016 (Actual)
Study Completion Date
September 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kiadis Pharma

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome
Keywords
Haploidentical stem cell transplantation, Graft-versus-host disease, Immune reconstitution, Alloreactive T-cells, Photodepletion, Photodynamic treatment, TH9402, Transplant-related mortality, Hematologic malignancy

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ATIR
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
ATIR
Intervention Description
Donor T-lymphocytes depleted ex vivo of host alloreactive T-cells using photodynamic treatment. Single intravenous infusion with 2x10E6 viable T-cells/kg.
Primary Outcome Measure Information:
Title
Transplant-related Mortality (TRM)
Description
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.
Time Frame
At 6 months post HSCT
Secondary Outcome Measure Information:
Title
Immune Reconstitution
Description
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
Time Frame
Up to 24 months post HSCT
Title
Relapse-related Mortality (RRM)
Description
Defined as death due to disease relapse or disease progression. The Kaplan-Meier analysis resulted in estimates and 95% confidence intervals (CI)s.
Time Frame
6, 12 and 24 months post HSCT
Title
Overall Survival (OS)
Description
Defined as the time from HSCT until death from any cause. The Kaplan-Meier analysis resulted in estimates and 95% CIs.
Time Frame
6, 12 and 24 months post HSCT
Title
Progression-free Survival (PFS)
Description
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.
Time Frame
6, 12 and 24 months post HSCT
Title
Number of Participants With Viral, Fungal, and Bacterial Infections.
Time Frame
Up to 24 months post HSCT
Title
Number of Participants With Graft Versus Host Disease (GVHD)
Time Frame
Up to 24 months post HSCT

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Denis Claude Roy, Prof MD
Organizational Affiliation
Maisonneuve-Rosemont Hospital, Montreal Quebec
Official's Role
Study Chair
Facility Information:
Facility Name
Algemeen Ziekenhuis Sint-Jan
City
Brugge
ZIP/Postal Code
8000
Country
Belgium
Facility Name
Université Libre de Bruxelles - Institute Jules Bordet
City
Brussels
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Universitair Ziekenhuis Gasthuisberg
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Juravinski Hospital and Cancer Centre
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 1C3
Country
Canada
Facility Name
Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Maisonneuve-Rosemont Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Facility Name
Universitätsklinikum Würzburg
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
Hammersmith Hospital
City
London
ZIP/Postal Code
W12 ONN
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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