Safety and Efficacy of Donor T-lymphocytes Depleted ex Vivo of Host Alloreactive T-cells (ATIR) in Patients With a Hematologic Malignancy Who Received a Hematopoietic Stem Cell Transplantation From a Haploidentical Donor

NCT01794299 | Completed Phase 2 Results DMC

• 3 other identifiers: CR-AIR-0072012-004461-41File # 9427-K0980\1-21C
• Study Type: interventional
• Target: 31
• Locations: 4 countries
• Sites: 8

Brief Summary

The purpose of this study is to determine whether ATIR is safe and effective in reducing transplant-related mortality and improving overall survival, when infused in patients with a hematologic malignancy following a T-cell depleted stem cell graft from a related haploidentical donor.

Conditions

Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndrome

Keywords

Haploidentical stem cell transplantation; Graft-versus-host disease; Immune reconstitution; Alloreactive T-cells; Photodepletion; Photodynamic treatment; TH9402; Transplant-related mortality; Hematologic malignancy

Outcome Measures

Primary Outcomes (1)

• Transplant-related Mortality (TRM)

  TRM is defined as death due to causes other than disease relapse or progression, or other causes which are unrelated to the transplantation procedure (e.g. accident, suicide). The TRM rate is displayed as a function of time using the Kaplan-Meier method. The TRM rate at 6 months post HSCT is estimated from this analysis.

  At 6 months post HSCT

Secondary Outcomes (6)

• Immune Reconstitution

  Up to 24 months post HSCT

• Relapse-related Mortality (RRM)

  6, 12 and 24 months post HSCT

• Overall Survival (OS)

  6, 12 and 24 months post HSCT

• Progression-free Survival (PFS)

  6, 12 and 24 months post HSCT

• Number of Participants With Viral, Fungal, and Bacterial Infections.

  Up to 24 months post HSCT

Study Arms (1)

ATIR

EXPERIMENTAL

Biological: ATIR

Interventions

ATIR BIOLOGICAL

Donor T-lymphocytes depleted ex vivo of host alloreactive T-cells using photodynamic treatment. Single intravenous infusion with 2x10E6 viable T-cells/kg.

ATIR

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: a) Acute myeloid leukemia (AML) in first remission with high-risk features or in second or higher remission b) Acute lymphoblastic leukemia (ALL) in first remission with high-risk features or in second or higher remission c) Myelodysplastic syndrome (MDS): transfusion-dependent, or intermediate or higher Revised International Prognostic Scoring System (IPSS-R) risk group
• Eligible for haploidentical stem cell transplantation according to the investigator

You may not qualify if:

• Availability of a suitable matched related or unrelated donor following a donor search
• In second or higher remission with the previous remission having lasted less than 6 months
• Diffusing capacity for carbon monoxide (DLCO) \< 50% predicted
• Left ventricular ejection fraction \< 50% (evaluated by echocardiogram or multiple gated acquisition \[MUGA\])
• Aspartate aminotransferase (AST) \> 2.5 x upper limit of normal (ULN)(CTCAE grade 2)
• Bilirubin \> 1.5 x ULN (CTCAE grade 2)
• Creatinine clearance \< 50 mL/min (calculated or measured)
• Positive test for human immunodeficiency virus (HIV)
• Positive pregnancy test (women of childbearing age only)
• Prior allogeneic stem cell transplantation using stem cells from a matched sibling donor, a matched unrelated donor, a haploidentical donor, or a cord blood donor
• Prior autologous stem cell transplantation
• Stay at intensive care unit for more than 2 months in the preceding 12 months
• Estimated probability of surviving less than 3 months
• Known allergy to any of the components of ATIR (e.g., dimethyl sulfoxide)
• Any other condition which, in the opinion of the investigator, makes the patient ineligible for the study

Sponsors & Collaborators

• Kiadis Pharma: lead

Study Sites (8)

Algemeen Ziekenhuis Sint-Jan

Bruges, 8000, Belgium

Location

Université Libre de Bruxelles - Institute Jules Bordet

Brussels, 1000, Belgium

Location

Universitair Ziekenhuis Gasthuisberg

Leuven, 3000, Belgium

Location

Juravinski Hospital and Cancer Centre

Hamilton, Ontario, L8V 1C3, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Maisonneuve-Rosemont Hospital

Montreal, Quebec, H1T 2M4, Canada

Location

Universitätsklinikum Würzburg

Würzburg, 97080, Germany

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 Quebec

  STUDY CHAIR

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: February 14, 2013
• First Posted: February 18, 2013
• Study Start: March 1, 2013
• Primary Completion: June 1, 2016
• Study Completion: September 1, 2017
• Last Updated: April 12, 2021
• Results First Posted: January 12, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); BE (3); GB (1); CA (3)