Hematologic DiseasesPhase 1/2NCT00993486
Dose-ranging Study of a Single Administration of T-cell Add-back Depleted of Host Alloreactive Cells in Patients Undergoing a Peripheral Blood Stem Cell Transplant From a Related, Haploidentical Donor
A Phase 1/2 study testing Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR) in people with Hematologic Diseases and Hematologic Malignancies, run by Kiadis Pharma at 1 site in Canada.
Trial summary
The purpose of this study is to determine the maximum tolerated dose and evaluate the safety of the administration of donor lymphocytes depleted of alloreactive T-cells following a stem cell transplant from a related, haploidentical donor, in patients with severe hematologic malignancies. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Hematologic Diseases, Hematologic Malignancies
- What is being tested?
- Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteCanada
- Study dates
- Jan 2005to Apr 2013
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Any of the following hematologic malignancies: very high risk leukemia, acute leukemia, chronic myeloid leukemia (CML), lymphoma, multiple myeloma (MM), myelodysplastic syndrome (MDS)
- Incompatibility at two to three loci (HLA-A, B and/or DR) or a single DR locus of the unshared haplotype between the donor and recipient
- Life expectancy of at least 3 months
- Satisfactory performance status (ECOG ≤ 2);
Who cannot join
- Possibility of performing an allogeneic transplant with an HLA (human leukocyte antigen) matched sibling donor
- Availability of an 6/6 HLA-A, B and DRB1 matched unrelated donor within 2-3 months;
- Pregnancy
- Viral hepatitis (B or C)
- Active serious infectious process
- HIV positivity;
Show all 14Show fewer
- Systemic dysfunction (cardiac, pulmonary, hepatic and renal) contra-indicating allogeneic stem cell transplantation
- Prior allogeneic transplantation
- Prior autologous transplantation within twelve months of baseline visit
- Any abnormal condition or laboratory result that is considered by the principal investigator capable of altering patient condition or study outcome
- Active central nervous system (CNS) disease at baseline
- Participation in a trial with an investigational agent within 30 days prior to entry in the study
- Malignant cells in circulating peripheral blood (> 25%)
- Other active malignant disease that would severely limit life expectancy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I, Dose-ranging, Open-label, Study of a Single Administration of T-cells Add-back Depleted of Host Alloreactive Cells Using Theralux™ Therapy, Following Haploidentical Peripheral Blood Stem Cell Transplantation Submitted to CD34+ Cell Selection, in Patients With Severe Hematologic Malignancies
The purpose of this study is to determine the maximum tolerated dose and evaluate the safety of the administration of donor lymphocytes depleted of alloreactive T-cells following a stem cell transplant from a related, haploidentical donor, in patients with severe hematologic malignancies.
Read the detailed description
Allogeneic stem cell transplantation is the treatment of choice for many patients with leukemia and other hematologic malignancies. However, a major limitation of this therapy is that for a significant number of patients no fully HLA-matched donor can be found. The application of partially HLA-matched (haploidentical) family donors, who are virtually always available, has some complications. If there is no T-cell add-back it increases the risk for life-threatening infections and disease relapse, while in case of T-cell add-back the risk of graft-versus-host disease is raised.
Kiadis Pharma has developed a method to selectively deplete host alloreactive T-cells through photodynamic therapy, using TH9402 ex vivo. The donor lymphocyte preparation depleted of functional alloreactive T-cells (ATIR) are administered to the patient 4-6 weeks after the stem cell transplant. This method enables early immune reconstitution while preventing graft-versus-host disease.
- Conditions
- Hematologic Diseases, Hematologic Malignancies
- Being tested
- Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR)
- Keywords
- Haploidentical stem cell transplantation, Graft-versus-host disease, Immune reconstitution, Alloreactive T-cells, Photodepletion, TH9402, Transplant related mortality, Hematologic malignancy
- Medical subject headings
- Hematologic Diseases, Hematologic Neoplasms, Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR)Biological
Single intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| L1 (dose 1.0x10E4 T-cells/kg) | Experimental | Not described Receives: Biological: Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR) |
| L2 (dose 5.0x10E4 T-cells/kg) | Experimental | Not described Receives: Biological: Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR) |
| L3 (dose 1.3x10E5 T-cells/kg) | Experimental | Not described Receives: Biological: Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR) |
| L4 (dose 3.2x10E5 T-cells/kg) | Experimental | Not described Receives: Biological: Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR) |
| L5 (dose 7.9x10E5 T-cells/kg) | Experimental | Not described Receives: Biological: Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR) |
| L6 (dose 2.0x10E6 T-cells/kg) | Experimental | Not described Receives: Biological: Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR) |
| L7 (dose 5.0x10E6 T-cells/kg) | Experimental | Not described Receives: Biological: Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicity, defined as acute graft-versus-host disease grade III or IV
Measured: Within 30 days after ATIR infusion
Secondary outcomes (5)
Immune reconstitution
Measured: Until 60 months after ATIR infusion
Rate of disease relapse
Measured: Until 60 months after ATIR infusion
Occurrence and severity of graft-versus-host disease
Measured: Until 60 months after ATIR infusion
Occurrence of adverse drug reactions
Measured: Until 18 months after ATIR infusion
Incidence and severity of infections
Measured: Until 18 months after ATIR infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2009 (estimated)
- Study startJan 2005
- Primary completionOct 2008
- Study completionApr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hematologic DiseasesStudies 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 1/2
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kiadis Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Denis-Claude Roy, MD, Principal investigator, Maisonneuve-Rosemont Hospital, Montréal, Canada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00993486
- Sponsor's protocol ID
- CR-GVH-001
- Status last verified
- Jun 2013
- First submitted
- 9 Oct 2009
- Last updated
- 20 Jun 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Roy DC, Lachance S, Cohen S, Delisle JS, Kiss T, Sauvageau G, Busque L, Ahmad I, Bernard L, Bambace N, Boumedine RS, Guertin MC, Rezvani K, Mielke S, Perreault C, Roy J. Allodepleted T-cell immunotherapy after haploidentical haematopoietic stem cell transplantation without severe acute graft-versus-host disease (GVHD) in the absence of GVHD prophylaxis. Br J Haematol. 2019 Sep;186(5):754-766. doi: 10.1111/bjh.15970. Epub 2019 May 28.
PubMed 31135970
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I, Dose-ranging, Open-label, Study of a Single Administration of T-cells Add-back Depleted of Host Alloreactive Cells Using Theralux™ Therapy, Following Haploidentical Peripheral Blood Stem Cell Transplantation Submitted to CD34+ Cell Selection, in Patients With Severe Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT00993486
- Acronym / sponsor ID
- CR-GVH-001
- Conditions
- Hematologic Diseases, Hematologic Malignancies
- Keywords
- Haploidentical stem cell transplantation, Graft-versus-host disease, Immune reconstitution, Alloreactive T-cells, Photodepletion, TH9402, Transplant related mortality, Hematologic malignancy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Kiadis PharmaIndustry (pharma, biotech, devices)
- Study start
- Jan 2005
- Primary completion
- Oct 2008 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 12 Oct 2009 (estimated)
- Results
- Not posted in the source record
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 the maximum tolerated dose and evaluate the safety of the administration of donor lymphocytes depleted of alloreactive T-cells following a stem cell transplant from a related, haploidentical donor, in patients with severe hematologic malignancies.
Detailed description
Allogeneic stem cell transplantation is the treatment of choice for many patients with leukemia and other hematologic malignancies. However, a major limitation of this therapy is that for a significant number of patients no fully HLA-matched donor can be found. The application of partially HLA-matched (haploidentical) family donors, who are virtually always available, has some complications. If there is no T-cell add-back it increases the risk for life-threatening infections and disease relapse, while in case of T-cell add-back the risk of graft-versus-host disease is raised.
Kiadis Pharma has developed a method to selectively deplete host alloreactive T-cells through photodynamic therapy, using TH9402 ex vivo. The donor lymphocyte preparation depleted of functional alloreactive T-cells (ATIR) are administered to the patient 4-6 weeks after the stem cell transplant. This method enables early immune reconstitution while preventing graft-versus-host disease.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| L1 (dose 1.0x10E4 T-cells/kg) | Experimental | Biological: Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR) |
| L2 (dose 5.0x10E4 T-cells/kg) | Experimental | Biological: Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR) |
| L3 (dose 1.3x10E5 T-cells/kg) | Experimental | Biological: Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR) |
| L4 (dose 3.2x10E5 T-cells/kg) | Experimental | Biological: Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR) |
| L5 (dose 7.9x10E5 T-cells/kg) | Experimental | Biological: Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR) |
| L6 (dose 2.0x10E6 T-cells/kg) | Experimental | Biological: Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR) |
| L7 (dose 5.0x10E6 T-cells/kg) | Experimental | Biological: Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR) |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Any of the following hematologic malignancies: very high risk leukemia, acute leukemia, chronic myeloid leukemia (CML), lymphoma, multiple myeloma (MM), myelodysplastic syndrome (MDS)
- Incompatibility at two to three loci (HLA-A, B and/or DR) or a single DR locus of the unshared haplotype between the donor and recipient
- Life expectancy of at least 3 months
- Satisfactory performance status (ECOG ≤ 2);
Key exclusion criteria (14 listed)
- Possibility of performing an allogeneic transplant with an HLA (human leukocyte antigen) matched sibling donor
- Availability of an 6/6 HLA-A, B and DRB1 matched unrelated donor within 2-3 months;
- Pregnancy
- Viral hepatitis (B or C)
- Active serious infectious process
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 |
|---|---|---|
| Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR)Single intravenous infusion | Biological | L1 (dose 1.0x10E4 T-cells/kg), L2 (dose 5.0x10E4 T-cells/kg), L3 (dose 1.3x10E5 T-cells/kg), L4 (dose 3.2x10E5 T-cells/kg), L5 (dose 7.9x10E5 T-cells/kg), L6 (dose 2.0x10E6 T-cells/kg), L7 (dose 5.0x10E6 T-cells/kg) |
Primary outcome
Dose limiting toxicity, defined as acute graft-versus-host disease grade III or IV
Time frame: Within 30 days after ATIR infusion
5 secondary outcomes
Immune reconstitution
Time frame: Until 60 months after ATIR infusion
Rate of disease relapse
Time frame: Until 60 months after ATIR infusion
Occurrence and severity of graft-versus-host disease
Time frame: Until 60 months after ATIR infusion
Occurrence of adverse drug reactions
Time frame: Until 18 months after ATIR infusion
Incidence and severity of infections
Time frame: Until 18 months after ATIR infusion
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2013.
- Derived from this study: PubMed 31135970Roy DC, Lachance S, Cohen S, Delisle JS, Kiss T, Sauvageau G, Busque L, Ahmad I, Bernard L, Bambace N, Boumedine RS, Guertin MC, Rezvani K, Mielke S, Perreault C, Roy J. Allodepleted T-cell immunotherapy after haploidentical haematopoietic stem cell transplantation without severe acute graft-versus-host disease (GVHD) in the absence of GVHD prophylaxis. Br J Haematol. 2019 Sep;186(5):754-766. doi: 10.1111/bjh.15970. Epub 2019 May 28.
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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, MD principal investigator
Maisonneuve-Rosemont Hospital, Montréal, Canada
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Donor lymphocyte preparation depleted of functional host alloreactive T-cells (ATIR) in people with Hematologic Diseases and Hematologic Malignancies, run by Kiadis Pharma at 1 site in Canada.
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 4 inclusion and 14 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 20 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Dose limiting toxicity, defined as acute graft-versus-host disease grade III or IV (time frame: Within 30 days after ATIR infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00993486, which also lists 1 linked publication.
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 20 Jun 2013.