Try our beta test site

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by Kiadis Pharma
Sponsor:
Information provided by (Responsible Party):
Kiadis Pharma
ClinicalTrials.gov Identifier:
NCT02500550
First received: July 14, 2015
Last updated: August 4, 2016
Last verified: August 2016
  Purpose
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.

Condition Intervention Phase
Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Myelodysplastic Syndrome
Biological: ATIR101
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: An Exploratory, Open-label, Multicenter Study to Evaluate the Safety and Efficacy of a Two-dose Regimen of ATIR101, a T-lymphocyte Enriched Leukocyte Preparation Depleted ex Vivo of Host Alloreactive T-cells (Using Photodynamic Treatment), in Patients With a Hematologic Malignancy, Who Received a CD34-selected Hematopoietic Stem Cell Transplantation From a Haploidentical Donor

Resource links provided by NLM:


Further study details as provided by Kiadis Pharma:

Primary Outcome Measures:
  • Incidence of acute graft versus host disease (GvHD) grade III/IV [ Time Frame: 180 days post HSCT ]

Secondary Outcome Measures:
  • Incidence of acute and chronic GvHD [ Time Frame: 12 months post HSCT ]
  • Severity of acute and chronic GvHD [ Time Frame: 12 months post HSCT ]
  • Time to T-cell reconstitution, [ Time Frame: 12 months post HSCT ]
    Defined as the time to CD3+ in peripheral blood higher than 0.2×10E9/L (at two consecutive measurements; time to first measurement)

  • Incidence of viral, fungal, and bacterial infections [ Time Frame: 12 months post HSCT ]
  • Severity of viral, fungal, and bacterial infections [ Time Frame: 12 months post HSCT ]
  • Transplant-related mortality (TRM) [ Time Frame: 12 months post HSCT ]
    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)

  • Relapse-related mortality (RRM) [ Time Frame: 12 months post HSCT ]
    Defined as death due to disease relapse or disease progression

  • Overall survival (OS) [ Time Frame: 12 months post HSCT ]
    Defined as the time from HSCT until death from any cause

  • Progression-free survival (PFS) [ Time Frame: 12 months post HSCT ]
    Defined as the time from HSCT until relapse, disease progression, or death, whichever occurs first

  • GvHD-free, relapse-free survival (GRFS) [ Time Frame: 12 months post HSCT ]
    Defined as the time until acute GvHD grade III/IV, chronic GvHD requiring systemic treatment, relapse, or death, whichever occurs first


Estimated Enrollment: 15
Study Start Date: October 2015
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ATIR101 Biological: ATIR101
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).

Detailed Description:

Study CR-AIR-008 is an exploratory, open-label, multicenter study. After signing informed consent, patients will receive a hematopoietic stem cell transplantation (HSCT) from a related, haploidentical donor, followed by a first ATIR101 infusion at a dose of 2×10E6 viable T-cells/kg between 28 and 32 days after the HSCT. Patients will receive a second ATIR101 infusion at a dose of 2×10E6 viable T-cells/kg between 70 and 74 days after the HSCT. To evaluate safety of the second dose administration, the first 6 patients treated will be evaluated for the occurrence of dose limiting toxicity (DLT), defined as acute GvHD grade III/IV within 120 days post HSCT (or within 42 days after the second ATIR101 infusion in case of prior dose delays). If within the first 6 patients no DLT is observed, treatment of the remaining 9 patients will continue with two ATIR101 doses of 2×10E6 viable T cells/kg. If within the first 6 patients at least 2 patients show DLT, the second ATIR101 infusion will be adjusted to a dose of 1×10E6 viable T cells/kg. If in one of the next 3 patients treated at this lower dose again DLT is observed, the second ATIR101 infusion will be halted and the remaining patients will be given only a single dose of ATIR101.

All patients treated with ATIR101 will be followed up until 12 months after the HSCT. Assessments will be performed at weekly visits from the day of the first ATIR101 infusion (Week 4) until 6 weeks after the second ATIR101 infusion (Week 16), at monthly visits from 4 until 6 months after the HSCT, and every 3 months from 6 until 12 months after the HSCT.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Inclusion Criteria Donor:

  • 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)
  • Eligible for donations of human blood and blood components according to local requirements and regulations
  • Eligible for donation according to the transplantation center

Exclusion Criteria Donor:

  • Positive pregnancy test or nursing (women of childbearing age only)
  • Positive viral test for HIV-1, HIV-2, HBV, HCV, Treponema pallidum, HTLV 1 (if tested), HTLV-2 (if tested), or WNV (if tested)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02500550

Contacts
Contact: Jeroen Rovers, MD PhD +31 20 3140 250 j.rovers@kiadis.com

Locations
United States, Massachusetts
Dana-Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02215
Contact: Sarah Nikiforow, MD         
Belgium
Algemeen Ziekenhuis Sint-Jan Recruiting
Bruges, Belgium, 8000
Principal Investigator: Dominik Selleslag, MD         
Institut Jules Bordet Recruiting
Brussels, Belgium, 1000
Principal Investigator: Philippe Lewalle, MD         
Centre Hospitalier Universitaire de Liège Recruiting
Liège, Belgium, 4000
Principal Investigator: Yves Beguin, MD         
Universitair Ziekenhuis Gasthuisberg Recruiting
Louvain, Belgium, 3000
Principal Investigator: Johan Maertens, MD         
Canada, Ontario
Juravinski Hospital and Cancer Centre Recruiting
Hamilton, Ontario, Canada, L8V 1C3
Principal Investigator: Irwin Walker, MD         
Canada, Quebec
Maisonneuve-Rosemont Hospital Recruiting
Montreal, Quebec, Canada, H1T 2M4
Principal Investigator: Denis Claude Roy, Prof MD         
Croatia
University Hospital Centre Zagreb Not yet recruiting
Zagreb, Croatia, 10000
Contact: Radovan Vrhovac, Prof MD         
Germany
Universitätsklinikum Schleswig-Holstein Campus Kiel Not yet recruiting
Kiel, Germany, 24105
Contact: Andreas Guenther, MD         
University Medical Center Mainz Not yet recruiting
Mainz, Germany, 55131
Contact: Eva Maria Wagner, MD         
Universitätsklinikum Würzburg Recruiting
Würzburg, Germany, 97080
Principal Investigator: Stephan Mielke, Prof MD         
Israel
Chaim Sheba Medical Center Not yet recruiting
Tel Hashomer, Israel, 5265601
Contact: Arnon Nagler, Prof MD         
United Kingdom
Heartlands Hospital Not yet recruiting
Birmingham, United Kingdom, B9 5SS
Contact: Bhuvan Kishore, MD         
Hammersmith Hospital Recruiting
London, United Kingdom, W12 ONN
Principal Investigator: Eduardo Olavarria, MD         
Sponsors and Collaborators
Kiadis Pharma
Investigators
Principal Investigator: Denis Claude Roy, MD PhD Maisonneuve-Rosemont Hospital (Montreal, Canada)
Principal Investigator: Stephan Mielke, MD PhD Julius Maximilian University of Würzburg (Würzburg, Germany)
  More Information

Responsible Party: Kiadis Pharma
ClinicalTrials.gov Identifier: NCT02500550     History of Changes
Other Study ID Numbers: CR-AIR-008
Study First Received: July 14, 2015
Last Updated: August 4, 2016

Keywords provided by Kiadis Pharma:
Haploidentical stem cell transplantation
Graft versus host disease
Immune reconstitution
Alloreactive T-cells
Photodynamic treatment
Hematologic malignancy
Transplant-related mortality

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on March 30, 2017