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

NCT02999854 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: CR-AIR-0092016-004672-21
• Study Type: interventional
• Target: 63
• Locations: 13 countries
• Sites: 42

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.

Conditions

Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndrome

Keywords

Haploidentical stem cell transplantation; Graft-versus-host disease; Immune reconstitution; Alloreactive T-cells; Photodynamic treatment; Hematologic malignancy; Transplant-related mortality; Overall survival; GRFS; GVHD

Outcome Measures

Primary Outcomes (1)

• Graft-versus-host Disease-free, Relapse-free Survival (GRFS)

  Defined as the time until acute GVHD grade III/IV, chronic GVHD requiring systemic treatment, relapse, or death, whichever occurs first. Kaplan-Meier estimates (percentage of participants) of GRFS were calculated at 24 months post HSCT.

  24 months post-HSCT

Secondary Outcomes (4)

• Overall Survival (OS)

  24 months post-HSCT

• Progression-free Survival (PFS)

  24 months post-HSCT

• Relapse-related Mortality (RRM)

  Through study completion, at least two years post HSCT

• Transplant-related Mortality (TRM)

  24 months post-HSCT

Other Outcomes (11)

• Immune Reconstitution

  Through study completion, at least two years post HSCT

• Cumulative Incidence of Grade II-IV and Grade III-IV Acute Graft-versus-host-disease (GVHD)

  Through study completion, at least two years post HSCT

• Cumulative Incidence of Moderate/Severe Chronic GVHD

  Through study completion, at least two years post HSCT

Study Arms (2)

ATIR101

EXPERIMENTAL

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

Biological: ATIR101; Procedure: T-cell depleted HSCT from a related, haploidentical donor

PTCy

ACTIVE COMPARATOR

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

Drug: Cyclophosphamide; Procedure: T-cell replete HSCT from a related, haploidentical donor

Interventions

ATIR101 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)

ATIR101

Cyclophosphamide DRUG

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

PTCy

T-cell depleted HSCT from a related, haploidentical donor 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

ATIR101

T-cell replete HSCT from a related, haploidentical donor 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

PTCy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 may not qualify 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

Sponsors & Collaborators

• Kiadis Pharma: lead

Study Sites (42)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Moores UC San Diego Cancer Center

La Jolla, California, 92037-0698, United States

Location

UCLA Center for Health Sciences

Los Angeles, California, 90095, United States

Location

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109-1274, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Stony Brook University Hospital

Stony Brook, New York, 11794, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Universitair Ziekenhuis Antwerpen

Antwerp, 2650, Belgium

Location

Algemeen Ziekenhuis Sint-Jan

Bruges, 8000, Belgium

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Universitair Ziekenhuis Gasthuisberg

Leuven, 3000, Belgium

Location

Centre Hospitalier Universitaire de Liège

Liège, 4000, Belgium

Location

Maisonneuve-Rosemont Hospital

Montreal, Quebec, H1T 2M4, Canada

Location

University Hospital Centre Zagreb

Zagreb, 10000, Croatia

Location

APHP Hospital Saint Louis

Paris, 75475, France

Location

University Hospital Frankfurt, Goethe University

Frankfurt, Germany

Location

University Medical Center Mainz

Mainz, 55131, Germany

Location

Ludwig-Maximilians-University Hospital of Munich-Grosshadern

Munich, 81377, Germany

Location

Universitätsklinikum Würzburg

Würzburg, 97080, Germany

Location

Rambam Medical Center

Haifa, 3109601, Israel

Location

Hadassah Medical Center & Hadassah Hospital Ein Karem

Jerusalem, 91120, Israel

Location

Sourasky Medical Center & Tel Aviv University

Tel Aviv, 6423906, Israel

Location

Chaim Sheba Medical Center

Tel Litwinsky, 5265601, Israel

Location

Milano Hospital, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Academisch Ziekenhuis Maastricht

Maastricht, 6229 HX, Netherlands

Location

Faculdade de Medicina da Universidade de Lisboa

Lisbon, 1649-028, Portugal

Location

University Hospital Barcelona Vall d' Hebron

Barcelona, 08035, Spain

Location

Hospital Puerta de Hierro Majadahonda

Madrid, 28220, Spain

Location

UGC Hematología y Hemoterapia

Seville, 41013, Spain

Location

Servicio de Hematología Hospital, Universitari I politècnic La Fe

Valencia, 46026, Spain

Location

Karolinska University Hospital

Stockholm, SE-141 86, Sweden

Location

Heartlands Hospital

Birmingham, B9 5SS, United Kingdom

Location

St James University Hospital

Leeds, LS9 7TF, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, L7 8XP, United Kingdom

Location

Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

Manchester Royal Infirmary

Manchester, M13 9WL, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Graft vs Host Disease; Hematologic Neoplasms

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Klaudia Traudtner, MD. Head of Safety and Pharmacovigilance.
• Organization: Kiadis Pharma Netherlands B.V

k.traudtner@kiadis.com

+31 (0)20 240 52 50

Study Officials

• Denis Claude Roy, Prof MD

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

  PRINCIPAL INVESTIGATOR

• Stephan Mielke, Prof MD

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2016
• First Posted: December 21, 2016
• Study Start: November 29, 2017
• Primary Completion: November 9, 2021
• Study Completion: December 17, 2021
• Last Updated: May 24, 2022
• Results First Posted: May 24, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (12); DE (4); PT (1); CR (1); IL (4); CA (1); BE (5); ES (4); SE (1); IT (2); NL (1); FR (1); GB (5)