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

• Status: Active, not recruiting
• Trial end date: 2021-11-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary 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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Kiadis Pharma
• Treatments: Cyclophosphamide

Criteria

Inclusion Criteria:

• 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 Revised International Prognostic Scoring System (IPSS-R) risk group

• Clinical justification of allogeneic stem cell transplantation where a suitable HLA matched sibling or unrelated donor is unavailable in a timely manner

• 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 human leukocyte antigen (HLA)-typing

• Karnofsky Performance Status (KPS) ≥ 70%

• Male or female, age ≥ 18 years and ≤ 70 years. Patients aged ≥ 65 years must have a Sorror score ≤ 3

• Patient weight ≥ 25 kg and ≤ 130 kg

• 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.

• For females of childbearing potential who are sexually active and males who have sexual contact with a female of childbearing potential: willingness to use of reliable methods of contraception (oral contraceptives, intrauterine device, hormone implants, contraceptive injection or abstinence) during study participation

• Given written informed consent (patient and donor)

Exclusion Criteria:

• Diagnosis of chronic myelomonocytic leukemia (CMML)

• Availability of a suitable HLA-matched sibling or unrelated donor in a donor search

• Prior allogeneic hematopoietic stem cell transplantation

• Diffusing capacity for carbon monoxide (hemoglobin corrected DLCO) < 50% predicted

• Left ventricular ejection fraction < 45% (evaluated by echocardiogram or MUGA scan)

• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2.5 × upper limit of normal (CTCAE grade 2)

• Creatinine clearance < 50 ml/min (calculated or measured)

• Positive pregnancy test or breastfeeding of patient or donor (women of childbearing age only)

• Estimated probability of surviving less than 3 months

• Known allergy to any of the components of ATIR101 (e.g., dimethyl sulfoxide)

• Known hypersensitivity to cyclophosphamide or any of its metabolites

• Any contraindication for GVHD prophylaxis with mycophenolate mofetil, cyclosporine A, or tacrolimus

• Known presence of HLA antibodies against the non-shared donor haplotype

• Positive viral test of the patient or donor for human immunodeficiency virus (HIV)-1, HIV-2, hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum, human T-lymphotropic virus (HTLV)-1 (if tested), HTLV-2 (if tested), West Nile virus (WNV; if tested), or Zika virus (if tested)

• Any other condition that, in the opinion of the investigator, makes the patient or donor ineligible for the study