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

Trial ID or NCT#

NCT02999854,

Status

not recruiting iconNOT RECRUITING

Purpose

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.

Official Title

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

Eligibility Criteria

Ages Eligible for Study: 18 Years to 70 Years
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
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 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:
  1. - 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

Investigator(s)

Laura Johnston
Laura Johnston
Blood and marrow transplant specialist, Blood and marrow transplant specialist, Medical oncologist, Hematologist
Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

Contact us to find out if this trial is right for you.

CONTACT

Michelle Chin
(650) 721-4183