Safety and efficacy of ATIR101 as adjunctive treatment to blood stem cell transplantation from a haploidentical family donor compared to post-transplant cyclophosphamide in patients with blood cancer

Phase 1

• Conditions: MedDRA version: 20.0Level: LLTClassification code 10000845Term: Acute lymphoblastic leukemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10059044Term: Allogeneic peripheral hematopoietic stem cell transplantSystem Organ Class: 10042613 - Surgical and medical procedures; Patients with a hematologic malignancy (AML, ALL, or MDS) who are eligible for a haploidentical HSCT; MedDRA version: 20.0Level: PTClassification code 10028533Term: Myelodysplastic syndromeSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10027703Term: Mismatched donor bone marrow transplantation therapySystem Organ Class: 10042613 - Surgical and medical procedures; MedDRA version: 20.0Level: PTClassification code 10000880Term: Acute myeloid leukaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2016-004672-21-BE
• Lead Sponsor: Kiadis Pharma Netherlands B.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-02-06
• Last Update Posted: 13 December 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 195

Inclusion Criteria

1. Any of the following hematologic malignancies:
- Acute myeloid leukemia (AML) in first cytomorphological remission (< 5% blasts in
the bone marrow) with Disease Risk Index (DRI) intermediate or above, or in second
or higher cytomorphological remission
- Acute lymphoblastic leukemia (ALL) in first or higher remission (< 5% blasts in the
bone marrow)
- Myelodysplastic syndrome (MDS): transfusion-dependent (requiring at least one
transfusion per month), or intermediate or higher IPSS-R risk group
2. Clinical justification of allogeneic stem cell transplantation where a suitable HLA matched sibling or unrelated donor is unavailable in a timely manner. An unrelated donor search is not required for a patient to be eligible if the clinical situation dictates an urgent transplantation. Clinical urgency is defined as 6-8 weeks from referral to transplant center or low likelihood of finding a matched unrelated donor
3. Availability of a related haploidentical donor with = 4/8 but < 7/8, or = 5/10 but < 9/10 matches at the HLA-A, -B, -C, -DRB1, and/or -DQB1 loci, as determined by high resolution HLA-typing
4. Karnofsky Performance Status (KPS) = 70%
5. Male or female, age = 18 years and = 70 years
Patients aged = 65 years must have a Sorror score = 3
6. Availability of a donor aged = 16 years and = 75 years who is eligible according to local requirements and regulations
7. For females of childbearing potential who are sexually active and males who have sexual contact with a female of childbearing potential: willingness to use reliable methods of contraception (oral contraceptives, intrauterine device, hormone implants, contraceptive injection or abstinence) during study participation
8. Given written informed consent (patient and donor)
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 185
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

1. Availability of a suitable fully matched related or unrelated donor in a donor search
2. Prior allogeneic hematopoietic stem cell transplantation
3. Diffusing capacity for carbon monoxide (hemoglobin corrected DLCO) < 50% predicted
4. Left ventricular ejection fraction < 50% (evaluated by echocardiogram or MUGA)
5. AST and/or ALT > 2.5 × ULN (CTCAE grade 2)
6. Bilirubin > 1.5 × ULN (CTCAE grade 2)
7. Creatinine clearance < 50 ml/min (calculated or measured)
8. Positive pregnancy test or breastfeeding of patient or donor (women of childbearing age only)
9. Estimated probability of surviving less than 3 months
10. Known allergy to any of the components of ATIR101 (e.g., dimethyl sulfoxide)
11. Known hypersensitivity to cyclophosphamide or any of its metabolites
12. Any contraindication for GVHD prophylaxis with mycophenolate mofetil,
cyclosporine A, or tacrolimus
13. Known presence of HLA antibodies against the non-shared donor haplotype
14. Positive HIV test
15. Positive viral test of the donor for HIV-1, HIV-2, HBV, HCV, Treponema pallidum, HTLV 1 (if tested), HTLV-2 (if tested), WNV (if tested), or Zika virus (if tested)
16. Any other condition that, in the opinion of the investigator, makes the patient or donor 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: The objective of this study is to compare safety and efficacy of a haploidentical T cell depleted HSCT and adjunctive treatment with ATIR101 versus a haploidentical T cell replete HSCT with post-transplant administration of high dose cyclophosphamide (PTCy) in patients with a hematologic malignancy. An additional objective of the study is to compare the effect of the two treatments on quality of life.;Secondary Objective: Not applicable;Primary end point(s): The primary endpoint of the study is GVHD-free, relapse-free survival (GRFS). GRFS is defined as time from randomization until grade III/IV acute graft-versus-host disease (GVHD), chronic GVHD requiring systemic immunosuppressive treatment, disease relapse, or death, whichever occurs first. This endpoint captures both safety and efficacy.;Timepoint(s) of evaluation of this end point: Throughout the study (no fixed timepoint)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Overall survival (safety and efficacy), defined as the time from randomization until death from any cause<br>• Progression-free survival (efficacy), defined as the time from randomization until relapse, disease progression, or death, whichever occurs first<br>• Relapse-related mortality (efficacy), defined as the time from randomization to death due to disease relapse or disease progression<br>• Transplant-related mortality (safety and efficacy), defined as the time from randomization to death due to causes other than disease relapse or disease progression<br>;Timepoint(s) of evaluation of this end point: Throughout the study (no fixed timepoint)