A Phase III, multicenter, randomized controlled study to compare safety and efficacy of a haploidentical HSCT and adjunctive treatment with ATIR101, a T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells, versus a haploidentical HSCT with post-transplant cyclophosphamide in patients with a hematologic malignancy (HATCY studie)

Phase 3

• Conditions: AML and MDS; Leukemia/Blood cancer; more specifically ALL; 10024324; more specifically A

• Registration Number: NL-OMON48941
• Lead Sponsor: Kiadis Pharma Netherlands B.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 2022-02-21
• Last Update Posted: 28 February 2024

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 4

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
bonemarrow)
- 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
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 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
9. Given written informed consent (patient and donor)

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, HBV (active
viral replication by PCR), HCV (active viral replication by PCR), Treponema
pallidum, HTLV 1 (if tested), HTLV-2 (if tested), WNV (if tested), or Zika
virus (if tested) (HBV/HCV: Only patients with active infection or infection
history and donors with active infection are excluded)
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
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoint of the study is GVHD-free, relapse-free survival (GRFS).<br /><br>GRFS is defined as time from randomization until grade III/IV acute<br /><br>graft-versus-host disease (GVHD), chronic GVHD requiring systemic<br /><br>immunosuppressive treatment, disease relapse, or death, whichever occurs first.<br /><br>This endpoint captures both safety and efficacy.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints:<br /><br><br /><br>Overall survival (OS)<br /><br>Progression-free survival (PFS)<br /><br>Relapse-related mortality (RRM)<br /><br>Transplant-related mortality (TRM)<br /><br>Immune reconstitution<br /><br>Incidence and severity of acute and chronic GVHD<br /><br>Incidence and severity of viral, fungal, and bacterial infections (efficacy)<br /><br>Incidence and severity of adverse events (safety)<br /><br>Quality of life</p><br>