Safety and Efficacy of Two Doses of ATIR101, a T-lymphocyte Enriched Leukocyte Preparation Depleted of Host Alloreactive T-cells, in Patients With a Hematologic Malignancy Who Received a Hematopoietic Stem Cell Transplantation From a Haploidentical Donor

NCT02500550 | Completed Phase 2 Results DMC

• 1 other identifier: CR-AIR-008
• Study Type: interventional
• Target: 15
• Locations: 6 countries
• Sites: 11

Brief Summary

The purpose of this study is to determine whether a repeat dose administration of ATIR101 is safe and effective when infused in patients with a hematologic malignancy following a T-cell depleted stem cell graft from a related haploidentical donor. All patients are planned to receive two ATIR101 doses of 2×10E6 viable T-cells/kg, unless the second dose is reduced or halted for safety reasons.

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

Outcome Measures

Primary Outcomes (1)

• Incidence of Acute Graft Versus Host Disease (GVHD) Grade III/IV

  180 days post HSCT

Secondary Outcomes (8)

• Incidence and Severity of Acute and Chronic GVHD

  Between 6 and 12 months after HSCT

• Percentage of Participants Who Achieved T-Cell Reconstitution at 6 and 12 Months Post HSCT

  6 and 12 months post HSCT

• Viral, Fungal, and Bacterial Infections

  From 6 months to 1 year after HSCT

• Transplant-related Mortality (TRM)

  12 months post HSCT

• Relapse-related Mortality (RRM)

  12 months post HSCT

Study Arms (1)

ATIR101

EXPERIMENTAL

Biological: ATIR101; Procedure: Haploidentical hematopoietic stem cell transplantation (HSCT); Procedure: TBI regime; Procedure: Non-TBI regime

Interventions

ATIR101 BIOLOGICAL

T-lymphocyte enriched leukocyte preparation depleted ex vivo of host alloreactive T-cells (using photodynamic treatment). Two intravenous infusions with 2x10E6 viable T-cells/kg approximately 42 days apart (unless the second dose is reduced or halted for safety reasons).

ATIR101

Haploidentical hematopoietic stem cell transplantation (HSCT) PROCEDURE

CD34-selected HSCT from a haploidentical donor. In order to prepare the patient for the HSCT one of the following myeloablative conditioning regimens is recommended: * Total Body Irradiation (TBI) regime * Non-TBI regime (See below for details)

ATIR101

TBI regime PROCEDURE

* Fractionated TBI 200 cGy twice daily for 3 days on Day -10 to -8 (1200 cGy in 6 fractions) * Fludarabine 30 mg/m2 IV once daily for 5 days on Day -7 to -3 * Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 * Anti-thymocyte globulin (ATG; Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.

ATIR101

Non-TBI regime PROCEDURE

* Fludarabine; 30 mg/m2 IV once daily for 5 days on Day -8 to -4 * Thiotepa; 5 mg/kg IV twice daily for 1 day on Day -7 * Melphalan; 60 mg/m2 IV once daily for 2 days on Day -2 and -1 * ATG (Thymoglobulin®); 2.5 mg/kg once daily for 4 days on Day -5 to -2, as a continuous IV infusion for 8 hours. During the course of ATG, patients will receive methylprednisolone 2 mg/kg/day IV.

ATIR101

Eligibility Criteria

• Age: 18 Years - 65 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 remission with high-risk features or in second or higher remission
• Acute lymphoblastic leukemia (ALL) in first remission with high-risk features or in second or higher remission
• Myelodysplastic syndrome (MDS): transfusion-dependent, or intermediate or higher IPSS-R risk group
• Karnofsky performance status ≥ 70%
• Eligible for haploidentical stem cell transplantation according to the investigator
• Male or female, age ≥ 18 years and ≤ 65 years

You may not qualify if:

• Availability of a fully matched related or unrelated donor following a donor search
• Diffusing capacity for carbon monoxide (DLCO) \< 50% predicted
• Left ventricular ejection fraction \< 50% (evaluated by echocardiogram or MUGA)
• AST \> 2.5 x ULN (CTCAE grade 2)
• Bilirubin \> 1.5 x ULN (CTCAE grade 2)
• Creatinine clearance \< 50 mL/min (calculated or measured)
• Positive HIV test
• Positive pregnancy test (women of childbearing age only)
• Prior allogeneic HSCT
• Estimated probability of surviving less than 3 months
• Known allergy to any of the components of ATIR101 (e.g., dimethyl sulfoxide)
• Known presence of HLA antibodies against the non-shared donor haplotype
• Any other condition which, in the opinion of the investigator, makes the patient ineligible for the study
• Haploidentical family donor with 2 to 3 mismatches at the HLA-A, -B and/or -DR loci of the unshared haplotype
• Male or female, age ≥ 16 and ≤ 75 years (If applicable, local legal requirements for donors under the age of 18 will be followed)

Sponsors & Collaborators

• Kiadis Pharma: lead

Study Sites (11)

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

Juravinski Hospital and Cancer Centre

Hamilton, Ontario, L8V 1C3, Canada

Location

Maisonneuve-Rosemont Hospital

Montreal, Quebec, H1T 2M4, Canada

Location

University Hospital Centre Zagreb

Zagreb, 10000, Croatia

Location

University Medical Center Mainz

Mainz, 55131, Germany

Location

Hospital de Santa Maria, Clinica Universitaria Hematologia

Lisbon, 1649-028, Portugal

Location

Heartlands Hospital

Birmingham, B9 5SS, United Kingdom

Location

Hammersmith Hospital

London, W12 ONN, United Kingdom

Location

MeSH Terms

Conditions

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

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

Results Point of Contact

• Title: Andrew Sandler, MD / Chief Medical Officer
• Organization: Kiadis Pharma Netherlands B.V.

a.sandler@kiadis.com

+1 206 779 9213

Study Officials

• Denis Claude Roy, Prof MD

  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 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2015
• First Posted: July 16, 2015
• Study Start: October 9, 2015
• Primary Completion: July 1, 2018
• Study Completion: December 17, 2018
• Last Updated: May 18, 2021
• Results First Posted: January 12, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

PT (1); CR (1); BE (4); GB (2); DE (1); CA (2)