Acute Myeloid LeukemiaPhase 2NCT01794299
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
A Phase 2 study testing ATIR in people with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia, run by Kiadis Pharma at 8 sites in 4 countries.
Trial 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. 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?
- ATIR
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 8 sitesin 4 countries
- Study dates
- Mar 2013to Sep 2017
- 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: 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
Who cannot join
- 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)
Show all 22Show fewer
- 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
- Donor inclusion criteria
- Haploidentical family donor with 2 to 3 mismatches at the human leukocyte antigen (HLA)-A, -B and/or -DR loci of the unshared haplotype
- Male or female, age ≥ 16 and ≤ 75 years
- Eligible for donation according to the transplantation center
- Donor exclusion criteria
- Positive viral test for HIV-1, HIV-2, hepatitis B virus (HBV), hepatitis C virus (HCV), Treponema pallidum, human T-lymphotropic virus (HTLV)-1*, HTLV-2*, or West Nile virus (WNV)* (if tested) (* at Canadian centers only)
- Positive pregnancy test or nursing (women of childbearing age only)
Trial locations and contacts
8 sites in 4 countries.
8 sites in 4 countries
Belgium3 sites
Algemeen Ziekenhuis Sint-Jan
Bruges, 8000
Université Libre de Bruxelles - Institute Jules Bordet
Brussels, 1000
Universitair Ziekenhuis Gasthuisberg
Leuven, 3000
Canada3 sites
Juravinski Hospital and Cancer Centre
Hamilton, Ontario, L8V 1C3
Maisonneuve-Rosemont Hospital
Montreal, Quebec, H1T 2M4
Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
About this study
Official title: An Exploratory, Open-label, Multicenter Study to Evaluate the Safety and Efficacy of ATIR, Donor T-lymphocytes Depleted ex Vivo of Host Alloreactive T-cells, 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 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.
Read the detailed description
Study CR-AIR-007 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 infusion with ATIR between 28 and 32 days after the HSCT (or later if required by the patient's medical condition). Patients will receive ATIR as a single infusion at a dose of 2x10E6 viable T-cells/kg. All patients treated with ATIR will be followed up until 12 months after the HSCT. Assessments will be performed at weekly visits from the day of ATIR infusion until 8 weeks after ATIR infusion, at monthly visits from 3 until 6 months after the HSCT, every 2 months from 6 until 12 months after the HSCT, and every 6 months from 12 until 24 months after the HSCT.
- Being tested
- ATIR
- Keywords
- Haploidentical stem cell transplantation, Graft-versus-host disease, Immune reconstitution, Alloreactive T-cells, Photodepletion, Photodynamic treatment, TH9402, Transplant-related mortality, Hematologic malignancy
- 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.
ATIRBiological
Donor T-lymphocytes depleted ex vivo of host alloreactive T-cells using photodynamic treatment. Single intravenous infusion with 2x10E6 viable T-cells/kg.
| Study group | Role | What they receive |
|---|---|---|
| ATIR | Experimental | Not described Receives: Biological: ATIR |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At 6 months post HSCT
Secondary outcomes (6)
Immune Reconstitution
Immunophenotyping on peripheral blood samples by means of flow cytometry assessment of immune subsets was done if the absolute lymphocyte count was higher than 0.1×10E9/l
Measured: Up to 24 months post HSCT
Relapse-related Mortality (RRM)
Defined as death due to disease relapse or disease progression. The Kaplan-Meier analysis resulted in estimates and 95% confidence intervals (CI)s.
Measured: 6, 12 and 24 months post HSCT
Overall Survival (OS)
Defined as the time from HSCT until death from any cause. The Kaplan-Meier analysis resulted in estimates and 95% CIs.
Measured: 6, 12 and 24 months post HSCT
Progression-free Survival (PFS)
Defined as the time from HSCT until relapse, disease progression, or death, whichever occurs first. The Kaplan-Meier analysis resulted in estimates and 95% CIs.
Measured: 6, 12 and 24 months post HSCT
Number of Participants With Viral, Fungal, and Bacterial Infections.
Measured: Up to 24 months post HSCT
Number of Participants With Graft Versus Host Disease (GVHD)
Measured: Up to 24 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 posted18 Feb 2013 (estimated)
- Study startMar 2013
- Primary completionJun 2016
- Study completionSep 2017
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
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kiadis Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Denis Claude Roy, Prof MD, Study chair, Maisonneuve-Rosemont Hospital, Montreal Quebec
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01794299
- Sponsor's protocol ID
- CR-AIR-007
- Other IDs
- 2012-004461-41, File # 9427-K0980\1-21C
- Status last verified
- Mar 2021
- First submitted
- 14 Feb 2013
- Last updated
- 12 Apr 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 12 Apr 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 ATIR, Donor T-lymphocytes Depleted ex Vivo of Host Alloreactive T-cells, in Patients With a Hematologic Malignancy, Who Received a CD34-selected Hematopoietic Stem Cell Transplantation From a Haploidentical Donor
- ClinicalTrials.gov ID
- NCT01794299
- Acronym / sponsor ID
- CR-AIR-007
- Keywords
- Haploidentical stem cell transplantation, Graft-versus-host disease, Immune reconstitution, Alloreactive T-cells, Photodepletion, Photodynamic treatment, TH9402, Transplant-related mortality
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Kiadis PharmaIndustry (pharma, biotech, devices)
- Study start
- Mar 2013 (actual)
- Primary completion
- Jun 2016 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 18 Feb 2013 (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 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.
Detailed description
Study CR-AIR-007 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 infusion with ATIR between 28 and 32 days after the HSCT (or later if required by the patient's medical condition). Patients will receive ATIR as a single infusion at a dose of 2x10E6 viable T-cells/kg. All patients treated with ATIR will be followed up until 12 months after the HSCT. Assessments will be performed at weekly visits from the day of ATIR infusion until 8 weeks after ATIR infusion, at monthly visits from 3 until 6 months after the HSCT, every 2 months from 6 until 12 months after the HSCT, and every 6 months from 12 until 24 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 |
|---|---|---|
| ATIR | Experimental | Biological: ATIR |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (22 listed)
- 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)
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 |
|---|---|---|
| ATIRDonor T-lymphocytes depleted ex vivo of host alloreactive T-cells using photodynamic treatment. Single intravenous infusion with 2x10E6 viable T-cells/kg. | Biological | ATIR |
Primary outcome
Transplant-related Mortality (TRM)
Time frame: At 6 months post HSCT
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.
6 secondary outcomes
Immune Reconstitution
Time frame: Up to 24 months post HSCT
Relapse-related Mortality (RRM)
Time frame: 6, 12 and 24 months post HSCT
Overall Survival (OS)
Time frame: 6, 12 and 24 months post HSCT
Progression-free Survival (PFS)
Time frame: 6, 12 and 24 months post HSCT
Number of Participants With Viral, Fungal, and Bacterial Infections.
Time frame: Up to 24 months post HSCT
Number of Participants With Graft Versus Host Disease (GVHD)
Time frame: Up to 24 months post HSCT
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 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 study chair
Maisonneuve-Rosemont Hospital, Montreal Quebec
8 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ATIR in people with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia, run by Kiadis Pharma at 8 sites in 4 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 2 inclusion and 22 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 12 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Belgium, Canada, Germany, United Kingdom. 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?
Transplant-related Mortality (TRM) (time frame: At 6 months 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 12 Apr 2021.