Acute Myeloid LeukemiaPhase 2NCT02500550
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
A Phase 2 study testing ATIR101, Haploidentical hematopoietic stem cell transplantation (HSCT) and TBI regime in people with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia, run by Kiadis Pharma at 11 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome
- What is being tested?
- ATIR101, Haploidentical hematopoietic stem cell transplantation (HSCT) and TBI regime
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 11 sitesin 6 countries
- Study dates
- 9 Oct 2015to 17 Dec 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 11Show fewer
- Male or female, age ≥ 18 years and ≤ 65 years
- 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
Who cannot join
- 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)
Show all 15Show fewer
- 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
- 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)
Trial locations and contacts
11 sites in 6 countries.
11 sites in 6 countries
Belgium4 sites
Algemeen Ziekenhuis Sint-Jan
Bruges, 8000
Institut Jules Bordet
Brussels, 1000
Universitair Ziekenhuis Gasthuisberg
Leuven, 3000
Centre Hospitalier Universitaire de Liège
Liège, 4000
Canada2 sites
Juravinski Hospital and Cancer Centre
Hamilton, Ontario, L8V 1C3
Maisonneuve-Rosemont Hospital
Montreal, Quebec, H1T 2M4
United Kingdom2 sites
Heartlands Hospital
Birmingham, B9 5SS
Hammersmith Hospital
London, W12 ONN
Portugal1 site
Hospital de Santa Maria, Clinica Universitaria Hematologia
Lisbon, 1649-028
About this study
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
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.
Read the 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.
- Being tested
- ATIR101, Haploidentical hematopoietic stem cell transplantation (HSCT), TBI regime, Non-TBI regime
- Keywords
- Haploidentical stem cell transplantation, Graft versus host disease, Immune reconstitution, Alloreactive T-cells, Photodynamic treatment, Hematologic malignancy, Transplant-related mortality
- Medical subject headings
- Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Myelodysplastic Syndromes, Graft vs Host Disease, Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ATIR101Biological
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).
Haploidentical hematopoietic stem cell transplantation (HSCT)Procedure or surgery
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)
TBI regimeProcedure or surgery
- 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.
Non-TBI regimeProcedure or surgery
- 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.
| Study group | Role | What they receive |
|---|---|---|
| ATIR101 | Experimental | Not described Receives: Biological: ATIR101; Procedure: Haploidentical hematopoietic stem cell transplantation (HSCT); Procedure: TBI regime; Procedure: Non-TBI regime |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Acute Graft Versus Host Disease (GVHD) Grade III/IV
Measured: 180 days post HSCT
Secondary outcomes (8)
Incidence and Severity of Acute and Chronic GVHD
Measured: Between 6 and 12 months after HSCT
Percentage of Participants Who Achieved T-Cell Reconstitution at 6 and 12 Months Post HSCT
Defined as CD3+ in peripheral blood higher than 0.2×10E9/L at 6 and 12 months post HSCT.
Measured: 6 and 12 months post HSCT
Viral, Fungal, and Bacterial Infections
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
Measured: From 6 months to 1 year after HSCT
Transplant-related Mortality (TRM)
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)
Measured: 12 months post HSCT
Relapse-related Mortality (RRM)
Defined as death due to disease relapse or disease progression
Measured: 12 months post HSCT
Overall Survival (OS)
Defined as the time from HSCT until death from any cause
Measured: 12 months post HSCT
Progression-free Survival (PFS)
Defined as the time from HSCT until relapse, disease progression, or death, whichever occurs first
Measured: 12 months post HSCT
GVHD-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
Measured: 12 months post HSCT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2015 (estimated)
- Study start9 Oct 2015
- Primary completionJul 2018
- Study completion17 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kiadis Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Denis Claude Roy, Prof MD, Principal investigator, Maisonneuve-Rosemont Hospital (Montreal, Canada)Stephan Mielke, Prof MD, Principal investigator, Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital (Stockholm, Sweden)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02500550
- Sponsor's protocol ID
- CR-AIR-008
- Status last verified
- May 2021
- First submitted
- 14 Jul 2015
- Last updated
- 18 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02500550
- Acronym / sponsor ID
- CR-AIR-008
- Keywords
- Haploidentical stem cell transplantation, Graft versus host disease, Immune reconstitution, Alloreactive T-cells, Photodynamic treatment, Hematologic malignancy, Transplant-related mortality
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Kiadis PharmaIndustry (pharma, biotech, devices)
- Study start
- 9 Oct 2015 (actual)
- Primary completion
- Jul 2018 (actual)
- Study completion
- 17 Dec 2018 (actual)
- First posted
- 16 Jul 2015 (estimated)
- Results
- Posted 12 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ATIR101 | Experimental | Biological: ATIR101, Procedure: Haploidentical hematopoietic stem cell transplantation (HSCT), Procedure: TBI regime, Procedure: Non-TBI regime |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Any of the following hematologic malignancies:
- Karnofsky performance status ≥ 70%
- Eligible for haploidentical stem cell transplantation according to the investigator
- Male or female, age ≥ 18 years and ≤ 65 years
- Haploidentical family donor with 2 to 3 mismatches at the HLA-A, -B and/or -DR loci of the unshared haplotype
Key exclusion criteria (15 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ATIR101T-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). | Biological | ATIR101 |
| Haploidentical hematopoietic stem cell transplantation (HSCT)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) | Procedure or surgery | ATIR101 |
| TBI regime* 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. | Procedure or surgery | ATIR101 |
| Non-TBI regime* 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. | Procedure or surgery | ATIR101 |
Primary outcome
Incidence of Acute Graft Versus Host Disease (GVHD) Grade III/IV
Time frame: 180 days post HSCT
8 secondary outcomes
Incidence and Severity of Acute and Chronic GVHD
Time frame: Between 6 and 12 months after HSCT
Percentage of Participants Who Achieved T-Cell Reconstitution at 6 and 12 Months Post HSCT
Time frame: 6 and 12 months post HSCT
Viral, Fungal, and Bacterial Infections
Time frame: From 6 months to 1 year after HSCT
Transplant-related Mortality (TRM)
Time frame: 12 months post HSCT
Relapse-related Mortality (RRM)
Time frame: 12 months post HSCT
Overall Survival (OS)
Time frame: 12 months post HSCT
Progression-free Survival (PFS)
Time frame: 12 months post HSCT
GVHD-free, Relapse-free Survival (GRFS)
Time frame: 12 months post HSCT
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Denis Claude Roy, Prof MD principal investigator
Maisonneuve-Rosemont Hospital (Montreal, Canada)
Stephan Mielke, Prof MD principal investigator
Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital (Stockholm, Sweden)
11 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ATIR101, Haploidentical hematopoietic stem cell transplantation (HSCT) and TBI regime in people with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia, run by Kiadis Pharma at 11 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Belgium, Canada, United Kingdom, Croatia, Germany and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Acute Graft Versus Host Disease (GVHD) Grade III/IV (time frame: 180 days post HSCT). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2021.