Clinical trial NCT01794299: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Kiadis Pharma
Sponsor class: INDUSTRY
First posted: 2013-02-18
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

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)

Primary outcomes:
measure: Transplant-related Mortality (TRM)
timeFrame: At 6 months post HSCT
Secondary outcomes:
measure: Immune Reconstitution
timeFrame: Up to 24 months post HSCT
measure: Relapse-related Mortality (RRM)
timeFrame: 6, 12 and 24 months post HSCT
measure: Overall Survival (OS)
timeFrame: 6, 12 and 24 months post HSCT
measure: Progression-free Survival (PFS)
timeFrame: 6, 12 and 24 months post HSCT
measure: Number of Participants With Viral, Fungal, and Bacterial Infections.
timeFrame: Up to 24 months post HSCT
measure: Number of Participants With Graft Versus Host Disease (GVHD)
timeFrame: Up to 24 months post HSCT
Other outcomes:
Locations:
city: Brugge
country: Belgium
facility: Algemeen Ziekenhuis Sint-Jan
city: Brussels
country: Belgium
facility: Université Libre de Bruxelles - Institute Jules Bordet
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Gasthuisberg
city: Hamilton
country: Canada
facility: Juravinski Hospital and Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Maisonneuve-Rosemont Hospital
state: Quebec
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
city: London
country: United Kingdom
facility: Hammersmith Hospital
Study officials:
affiliation: Maisonneuve-Rosemont Hospital, Montreal Quebec
name: Denis Claude Roy, Prof MD
role: STUDY_CHAIR
References: