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: Patients with a hematologic malignancy (AML, ALL, or MDS) who are eligible for a haploidentical HSCT; MedDRA version: 20.0 Level: LLT Classification code 10059044 Term: Allogeneic peripheral hematopoietic stem cell transplant System Organ Class: 10042613 - Surgical and medical procedures; MedDRA version: 20.0 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: PT Classification code 10027703 Term: Mismatched donor bone marrow transplantation therapy System Organ Class: 10042613 - Surgical and medical procedures; MedDRA version: 20.0 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: PT Classification code 10028533 Term: Myelodysplastic syndrome System 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-NL
• Lead Sponsor: Kiadis Pharma Netherlands BV

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-07-19
• Last Update Posted: 1 February 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 250

Inclusion Criteria

1. Any of the following hematologic malignancies:
- Acute myeloid leukemia (AML) in first cytomorphological remission (with < 5%
blasts in the bone marrow) with Disease Risk Index (DRI) intermediate or above, or
in second or higher cytomorphological remission (with < 5% blasts in the bone
marrow)
- Acute lymphoblastic leukemia (ALL) in first or higher remission (with < 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.
3. Availability of a related haploidentical donor with one fully shared haplotype and 2 to 4
mismatches at the HLA-A, -B, -C, and -DRB1 loci of the unshared haplotype, 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. Patient weight = 25 kg and = 130 kg
7. Availability of a donor aged = 16 years and = 75 years who is eligible according to local
requirements and regulations. Donors aged < 16 years are allowed if they are the only
option for an HSCT, if they are permitted by local regulations, and if the IRB/IEC
approves participation in the study.
8. For females of childbearing potential27 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
9. 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 237
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 13

Exclusion Criteria

1. Diagnosis of chronic myelomonocytic leukemia (CMML)
2. Availability of a suitable HLA-matched sibling or unrelated donor in a donor search
3. Prior allogeneic hematopoietic stem cell transplantation
4. Diffusing capacity for carbon monoxide (hemoglobin corrected DLCO) < 50% predicted
5. Left ventricular ejection fraction < 45% (evaluated by echocardiogram or MUGA scan)
6. AST and/or ALT > 2.5 × 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 viral test of the patient or donor for HIV-1, HIV-2, HBV28, HCV28, Treponema
pallidum, HTLV-1 (if tested), HTLV-2 (if tested), WNV (if tested), or Zika virus (if tested)
15. 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;Timepoint(s) of evaluation of this end point: Throughout the study (no fixed timepoint);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.

Secondary Outcome Measures

Name	Time	Method
<br> Secondary end point(s): Overall survival (safety and efficacy)<br> Overall survival (OS) is defined as the time from randomization until death from any cause.<br> Progression-free survival (efficacy)<br> Progression-free survival (PFS) is defined as the time from randomization until relapse, disease progression, or death, whichever occurs first.<br> Relapse-related mortality (efficacy)<br> Relapse-related mortality (RRM) is defined as the time from randomization to death due to disease relapse or disease progression.<br> Transplant-related mortality (safety and efficacy)<br> Transplant-related mortality (TRM) is 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)