Summary

for people ages 18-70 (full criteria)
at UCLA UCSD
study started
estimated completion
Carolyn Mulroney, MD(ucsd)Hyung C. Suh(ucla)

Description

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.

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

Details

Study CR-AIR-009 is a Phase III randomized controlled multicenter open-label study comparing two parallel groups. After signing informed consent, a total of 250 patients will be randomized in a 1:1 fashion to receive either a T-cell depleted hematopoietic stem cell transplantation (HSCT; CD34 selection) from a related, haploidentical donor, followed by ATIR101 infusion, or a T-cell replete HSCT, followed by a high dose of post-transplant cyclophosphamide (PTCy).

Randomization will use minimization to balance treatment groups with respect to underlying disease (AML, ALL, or MDS), Disease Risk Index (DRI; intermediate risk, high risk, or very high risk) and center. A stochastic treatment allocation procedure will be used so that the treatment assignment is random for all patients entered in the study.

Patients randomized in the ATIR101 group will receive a single ATIR101 dose of 2×10E6 viable T-cells/kg between 28 and 32 days after the HSCT. Patients randomized in the PTCy group will receive cyclophosphamide 50 mg/kg/day at 3 and 4/5 days after the HSCT. All patients will be followed up for at least 24 months post HSCT.

Keywords

Acute Myeloid Leukemia Acute Lymphoblastic Leukemia Myelodysplastic Syndrome Haploidentical stem cell transplantation Graft-versus-host disease Immune reconstitution Alloreactive T-cells Photodynamic treatment Hematologic malignancy Transplant-related mortality Overall survival GRFS GVHD Leukemia Leukemia, Myeloid, Acute Myelodysplastic Syndromes Preleukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Cyclophosphamide ATIR101 T-cell depleted HSCT from a related, haploidentical donor T-cell replete HSCT from a related, haploidentical donor PTCy

Eligibility

You can join if…

Open to people ages 18-70

  • 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)

You CAN'T join if...

  • 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

Locations

  • Moores UC San Diego Cancer Center not yet accepting patients
    La Jolla California 92037-0698 United States
  • UCLA Center for Health Sciences accepting new patients
    Los Angeles California 90095 United States

Lead Scientists

  • Carolyn Mulroney, MD (ucsd)
    Co-Investigator on several clinical trials in the Blood and Marrow Transplantation Division: BMTCTN 0402, IRB # 101006, A Phase III Randomized, Multicenter Trial comparing Sirolimus/Tacrolimus with Tacrolimus/Methotrexate as a Graft-Versus-Host Disease (GVHD) Prophylaxis After HLA- Matched, Related Peripheral Blood Stem Cell transplantation. B.A.
  • Hyung C. Suh (ucla)

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Kiadis Pharma
ID
NCT02999854
Phase
Phase 3
Study Type
Interventional
Last Updated