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

NCT ID: NCT02999854

Last Updated: 2022-05-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-29
• Study Completion Date: 2021-12-17

Brief 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.

Detailed Description

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.

Conditions

Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

ATIR101

T-cell depleted HSCT from a related, haploidentical donor, followed by IV infusion with ATIR101 at a single dose of 2×10E6 viable T-cells/kg body weight between 28 and 32 days after the HSCT

Group Type: EXPERIMENTAL

ATIR101

Intervention Type: BIOLOGICAL

ATIR101 is a T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells using photodynamic treatment; single dose of 2×10E6 viable T-cells/kg body weight between 28 and 32 days after the HSCT (intravenous infusion)

T-cell depleted HSCT from a related, haploidentical donor

Intervention Type: PROCEDURE

T-cell depleted graft prepared from peripheral blood stem cells using the CD34+ cell selection method; infused after a total body irradiation (TBI) or non-TBI conditioning regimen

PTCy

T-cell replete HSCT from a related, haploidentical donor, followed by IV infusion of post-transplant cyclophosphamide (PTCy) 50 mg/kg/day at 3 and 4/5 days after the HSCT

Group Type: ACTIVE_COMPARATOR

Cyclophosphamide

Intervention Type: DRUG

High dose post-transplant cyclophosphamide 50 mg/kg/day at 3 and 4/5 days after the HSCT (powder for intravenous infusion)

T-cell replete HSCT from a related, haploidentical donor

Intervention Type: PROCEDURE

T-cell replete (full, non-manipulated) graft prepared from either bone marrow or peripheral blood stem cells; infused after a total body irradiation (TBI) or non-TBI conditioning regimen

Interventions

ATIR101

ATIR101 is a T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells using photodynamic treatment; single dose of 2×10E6 viable T-cells/kg body weight between 28 and 32 days after the HSCT (intravenous infusion)

Intervention Type: BIOLOGICAL

Cyclophosphamide

High dose post-transplant cyclophosphamide 50 mg/kg/day at 3 and 4/5 days after the HSCT (powder for intravenous infusion)

Intervention Type: DRUG

T-cell depleted HSCT from a related, haploidentical donor

T-cell depleted graft prepared from peripheral blood stem cells using the CD34+ cell selection method; infused after a total body irradiation (TBI) or non-TBI conditioning regimen

Intervention Type: PROCEDURE

T-cell replete HSCT from a related, haploidentical donor

T-cell replete (full, non-manipulated) graft prepared from either bone marrow or peripheral blood stem cells; infused after a total body irradiation (TBI) or non-TBI conditioning regimen

Intervention Type: PROCEDURE

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kiadis Pharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Denis Claude Roy, Prof MD

Role: PRINCIPAL_INVESTIGATOR

Research Center and Cellular Therapy Laboratory, Maisonneuve-Rosemont Hospital (Montreal, Canada)

Stephan Mielke, Prof MD

Role: PRINCIPAL_INVESTIGATOR

Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital (Stockholm, Sweden)

Locations

City of Hope National Medical Center

Duarte, California, United States

Moores UC San Diego Cancer Center

La Jolla, California, United States

UCLA Center for Health Sciences

Los Angeles, California, United States

Stanford University School of Medicine

Stanford, California, United States

Emory University

Atlanta, Georgia, United States

University of Kansas Cancer Center

Westwood, Kansas, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Weill Cornell Medical College

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

Stony Brook University Hospital

Stony Brook, New York, United States

Oregon Health & Science University

Portland, Oregon, United States

Universitair Ziekenhuis Antwerpen

Antwerp, , Belgium

Algemeen Ziekenhuis Sint-Jan

Bruges, , Belgium

Institut Jules Bordet

Brussels, , Belgium

Universitair Ziekenhuis Gasthuisberg

Leuven, , Belgium

Centre Hospitalier Universitaire de Liège

Liège, , Belgium

Maisonneuve-Rosemont Hospital

Montreal, Quebec, Canada

University Hospital Centre Zagreb

Zagreb, , Croatia

APHP Hospital Saint Louis

Paris, , France

University Hospital Frankfurt, Goethe University

Frankfurt, , Germany

University Medical Center Mainz

Mainz, , Germany

Ludwig-Maximilians-University Hospital of Munich-Grosshadern

Munich, , Germany

Universitätsklinikum Würzburg

Würzburg, , Germany

Rambam Medical Center

Haifa, , Israel

Hadassah Medical Center & Hadassah Hospital Ein Karem

Jerusalem, , Israel

Sourasky Medical Center & Tel Aviv University

Tel Aviv, , Israel

Chaim Sheba Medical Center

Tel Litwinsky, , Israel

Milano Hospital, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Milan, , Italy

Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Academisch Ziekenhuis Maastricht

Maastricht, , Netherlands

Faculdade de Medicina da Universidade de Lisboa

Lisbon, , Portugal

University Hospital Barcelona Vall d' Hebron

Barcelona, , Spain

Hospital Puerta de Hierro Majadahonda

Madrid, , Spain

UGC Hematología y Hemoterapia

Seville, , Spain

Servicio de Hematología Hospital, Universitari I politècnic La Fe

Valencia, , Spain

Karolinska University Hospital

Stockholm, , Sweden

Heartlands Hospital

Birmingham, , United Kingdom

St James University Hospital

Leeds, , United Kingdom

Royal Liverpool University Hospital

Liverpool, , United Kingdom

Hammersmith Hospital

London, , United Kingdom

Manchester Royal Infirmary

Manchester, , United Kingdom

Countries

United States; Belgium; Canada; Croatia; France; Germany; Israel; Italy; Netherlands; Portugal; Spain; Sweden; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-004672-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR-AIR-009

Identifier Type: -

Identifier Source: org_study_id