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

March 17, 2021 updated by: Kiadis Pharma

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 Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brugge, Belgium, 8000
        • Algemeen Ziekenhuis Sint-Jan
      • Brussels, Belgium, 1000
        • Université Libre de Bruxelles - Institute Jules Bordet
      • Leuven, Belgium, 3000
        • Universitair Ziekenhuis Gasthuisberg
  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8V 1C3
        • Juravinski Hospital and Cancer Centre
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Hospital
    • Quebec
      • Montreal, Quebec, Canada, H1T 2M4
        • Maisonneuve-Rosemont Hospital
  • Germany
      • Würzburg, Germany, 97080
        • Universitatsklinikum Wurzburg
  • United Kingdom
      • London, United Kingdom, W12 ONN
        • Hammersmith Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Transplant-related Mortality (TRM)
Time Frame: At 6 months post HSCT
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
Time Frame: Up to 24 months post HSCT
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)
Time Frame: 6, 12 and 24 months post HSCT
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)
Time Frame: 6, 12 and 24 months post HSCT
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)
Time Frame: 6, 12 and 24 months post HSCT
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.
Time Frame: Up to 24 months post HSCT
Up to 24 months post HSCT
Number of Participants With Graft Versus Host Disease (GVHD)
Time Frame: Up to 24 months post HSCT
Up to 24 months post HSCT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kiadis Pharma

Investigators

  • Study Chair: Denis Claude Roy, Prof MD, Maisonneuve-Rosemont Hospital, Montreal Quebec

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2013

Primary Completion (Actual)

June 1, 2016

Study Completion (Actual)

September 1, 2017

Study Registration Dates

First Submitted

February 14, 2013

First Submitted That Met QC Criteria

February 15, 2013

First Posted (Estimate)

February 18, 2013

Study Record Updates

Last Update Posted (Actual)

April 12, 2021

Last Update Submitted That Met QC Criteria

March 17, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CR-AIR-007
  • 2012-004461-41 (EudraCT Number)
  • File # 9427-K0980\1-21C (Other Identifier: Health Canada)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Acute Myeloid Leukemia

Clinical Trials on ATIR

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kosovo

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe