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

Phase 1

Conditions: Patients with a hematologic malignancy (AML, ALL, or MDS) who are eligible for a haploidentical HSCT
MedDRA version: 17.0Level: LLTClassification code 10000845Term: Acute lymphoblastic leukemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 17.0Level: LLTClassification code 10059044Term: Allogeneic peripheral hematopoietic stem cell transplantSystem Organ Class: 10042613 - Surgical and medical procedures
MedDRA version: 17.0Level: PTClassification code 10027703Term: Mismatched donor bone marrow transplantation therapySystem Organ Class: 10042613 - Surgical and medical procedures
MedDRA version: 17.0Level: PTClassification code 10000880Term: Acute myeloid leukaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 17.0Level: PTClassification code 10028533Term: Myelodysplastic syndromeSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Registration Number: EUCTR2012-004461-41-BE

Lead Sponsor: Kiadis Pharma Netherlands B.V.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 30

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
• Eligible for haploidentical stem cell transplantation according to the investigator
• Male or female, age = 18 years and = 65 years
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 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 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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To study the safety and efficacy of ATIR at a dose of 2x10E6 viable T-cells/kg body weight in patients with a hematologic malignancy who received a haploidentical HSCT.;Secondary Objective: Not applicable;Primary end point(s): Transplant-related mortality (TRM) ;Timepoint(s) of evaluation of this end point: At 6 months post HSCT

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Incidence and severity of acute and chronic graft versus host disease (GvHD) <br>• Immune reconstitution<br>• Incidence and severity of viral, fungal, and bacterial infections<br>• TRM, relapse-related mortality (RRM), overall survival (OS), and progression-free survival (PFS)<br>;Timepoint(s) of evaluation of this end point: Up to 24 months post HSCT

Related Trials