- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02500550
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
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
Study Overview
Status
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Brugge, Belgium, 8000
- Algemeen Ziekenhuis Sint-Jan
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Brussels, Belgium, 1000
- Institut Jules Bordet
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Leuven, Belgium, 3000
- Universitair Ziekenhuis Gasthuisberg
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Liège, Belgium, 4000
- Centre Hospitalier Universitaire de Liège
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Ontario
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Hamilton, Ontario, Canada, L8V 1C3
- Juravinski Hospital and Cancer Centre
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Quebec
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Montreal, Quebec, Canada, H1T 2M4
- Maisonneuve-Rosemont Hospital
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Zagreb, Croatia, 10000
- University Hospital Centre Zagreb
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Mainz, Germany, 55131
- University Medical Center Mainz
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Lisboa, Portugal, 1649-028
- Hospital de Santa Maria, Clinica Universitaria Hematologia
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Birmingham, United Kingdom, B9 5SS
- Heartlands Hospital
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London, United Kingdom, W12 ONN
- Hammersmith Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: PREVENTION
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: ATIR101
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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).
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:
(See below for details)
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Incidence of Acute Graft Versus Host Disease (GVHD) Grade III/IV
Time Frame: 180 days post HSCT
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180 days post HSCT
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Incidence and Severity of Acute and Chronic GVHD
Time Frame: Between 6 and 12 months after HSCT
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Between 6 and 12 months after HSCT
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Percentage of Participants Who Achieved T-Cell Reconstitution at 6 and 12 Months Post HSCT
Time Frame: 6 and 12 months post HSCT
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Defined as CD3+ in peripheral blood higher than 0.2×10E9/L at 6 and 12 months post HSCT.
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6 and 12 months post HSCT
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Viral, Fungal, and Bacterial Infections
Time Frame: From 6 months to 1 year after HSCT
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Infection was defined as (1) a clinically apparent infectious disease with symptoms or (2) a viral reactivation.
Severity was graded according to CTCAE vs. 4.0
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From 6 months to 1 year after HSCT
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Transplant-related Mortality (TRM)
Time Frame: 12 months post HSCT
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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)
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12 months post HSCT
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Relapse-related Mortality (RRM)
Time Frame: 12 months post HSCT
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Defined as death due to disease relapse or disease progression
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12 months post HSCT
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Overall Survival (OS)
Time Frame: 12 months post HSCT
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Defined as the time from HSCT until death from any cause
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12 months post HSCT
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Progression-free Survival (PFS)
Time Frame: 12 months post HSCT
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Defined as the time from HSCT until relapse, disease progression, or death, whichever occurs first
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12 months post HSCT
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GVHD-free, Relapse-free Survival (GRFS)
Time Frame: 12 months post HSCT
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Defined as the time until acute GVHD grade III/IV, chronic GVHD requiring systemic treatment, relapse, or death, whichever occurs first
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12 months post HSCT
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: 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)
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Neoplasms by Site
- Bone Marrow Diseases
- Hematologic Diseases
- Leukemia, Lymphoid
- Neoplasms
- Myelodysplastic Syndromes
- Hematologic Neoplasms
- Leukemia
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
Other Study ID Numbers
- CR-AIR-008
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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