Hematological MalignancyPhase 1/2ILD-TK01NCT01086735
Suicide Gene Therapy for Donor Lymphocytes Infusion After Allogeneic Hematopoietic Stem Cell Transplantation
A Phase 1/2 study testing donor lymphocyte infusion in people with Hematological Malignancy, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The main complications of allogeneic hematopoietic stem cell transplantation (HSCT) include graft-versus-host disease (GVHD) and poor immune reconstitution leading to severe infections and leukemia relapse. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hematological Malignancy
- What is being tested?
- donor lymphocyte infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteFrance
- Study dates
- Feb 2010to Nov 2012
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Hematological malignancy.
- Previous allogeneic hematopoietic stem cell transplantation.
- Relapse diagnosed at the molecular, cytogenetic, or cytological level.
- Failure of a previous stdILD or inclusion in first intention without previous stdDLI.
- Age > 18 years and < 70 years at the time of inclusion. For patients between 15 and 18 years of age, a case-per case inclusion will be studied.
- Performance status considered on the score Eastern Cooperative Oncology Group (ECOG) < 2.
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- Life expectation 1-month-old superior.
- Signed written informed consent.
- Negative human chorionic gonadotropin (HCG) in the 7 days preceding the inclusion for women in age of procreation.
- Membership of the French national insurance.
Who cannot join
- Grade >II acute GVHD or chronic extensive GVHD at the time of inclusion.
- Patient receiving an immunosuppressive treatment for GVHD treatment at the time of inclusion.
- Dysfunction of liver (alanine aminotransferase / aspartate transaminase (ALAT/ASAT) > 5 N, or bilirubin > 50 µM), or of the renal function (creatinine clearance < 30 ml / min).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Suicide Gene Therapy for Donor Lymphocytes Infusion After Allogeneic Hematopoietic Stem Cell Transplantation: a Phase I/II Clinical Study
The main complications of allogeneic hematopoietic stem cell transplantation (HSCT) include graft-versus-host disease (GVHD) and poor immune reconstitution leading to severe infections and leukemia relapse. Mature donor T-cells present in the transplant facilitate T-cell reconstitution but also induce GVHD, which itself impairs immune reconstitution. We have developed a strategy of alloreactive T-cell depletion, using T-cells expressing the Herpes simplex thymidine kinase (TK) suicide gene combined with a ganciclovir (GCV) treatment. This system permits the selective elimination of dividing TK+ T-cells in vivo. To test this hypothesis in preclinical settings, we have previously developed several experimental models of GVHD using TK+ T-cells in mice. The demonstration that a preventive treatment with GCV administered close to the time of HSCT could control GVHD brought the proof of concept. We now propose a clinical trial to test whether donor lymphocytes infusion (DLI) using TK-transduced cells permits to induce a graft-versus-tumor (GVT) effect for treatment of relapse after HSCT, while GVHD can be controlled by GCV treatment.
Read the detailed description
DLI-TK is administered either after failure of 1 or several previous standard (std-) DLI of, defined after a minimal follow-up of 2 months after the last injection. To prepare DLI-TK, donor T-cells are transduced with a retroviral vector encoding TK. Transduced cells are selected using a CliniMACS device (MYLTENYI). In case of previous std-DLI received, the DLI-TK cell dose is adjusted to be below or equal to the maximal cell dose previously received in std-DLI. No comparison is planned in the analysis.
- Conditions
- Hematological Malignancy
- Being tested
- donor lymphocyte infusion
- Keywords
- hematological malignancy, allogeneic hematopoietic stem cell transplantation, donor lymphocyte infusion, antitumor immunotherapy, graft-versus-tumor effect, gene therapy, relapse, adult
- Medical subject headings
- Hematologic Neoplasms, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
donor lymphocyte infusionBiological
Donor T-cell transduction
| Study group | Role | What they receive |
|---|---|---|
| donor lymphocyte infusion | Experimental | Donor T-cell transduction Receives: Biological: donor lymphocyte infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of "severe" GHVD (acute grade >II or chronic extensive) following DLI-TK and treatment with GCV
Incidence of "severe" GHVD (acute grade >II or chronic extensive) following DLI-TK and treatment with GCV
Measured: during the 12 months of follow-up
Secondary outcomes (3)
The incidence of GVHD of any grade after DLI-TK
The incidence of GVHD of any grade after DLI-TK
Measured: during the 12 months of follow-up
The anti-tumoral efficiency of DLI-TK to treat the relapse of the hematological malignancy
The anti-tumoral efficiency of DLI-TK to treat the relapse of the hematological malignancy
Measured: during the 12 months of follow-up
The survival and the survival without disease after DLI-TK
The survival and the survival without disease after DLI-TK
Measured: during the 12 months of follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2010 (estimated)
- Study startFeb 2010
- Primary completionNov 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematological MalignancyStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Paris 12 Val de Marne University, Pierre and Marie Curie University
- Responsible party
- Sponsor
- Investigators
- Sébastien Maury, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01086735
- Sponsor's protocol ID
- P010506
- Acronym
- ILD-TK01
- Status last verified
- Jan 2013
- First submitted
- 12 Mar 2010
- Last updated
- 14 Jan 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Suicide Gene Therapy for Donor Lymphocytes Infusion After Allogeneic Hematopoietic Stem Cell Transplantation: a Phase I/II Clinical Study
- ClinicalTrials.gov ID
- NCT01086735
- Acronym / sponsor ID
- ILD-TK01 / P010506
- Conditions
- Hematological Malignancy
- Keywords
- hematological malignancy, allogeneic hematopoietic stem cell transplantation, donor lymphocyte infusion, antitumor immunotherapy, graft-versus-tumor effect, gene therapy, relapse, adult
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Paris 12 Val de Marne University, Pierre and Marie Curie University
- Study start
- Feb 2010
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 15 Mar 2010 (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 main complications of allogeneic hematopoietic stem cell transplantation (HSCT) include graft-versus-host disease (GVHD) and poor immune reconstitution leading to severe infections and leukemia relapse. Mature donor T-cells present in the transplant facilitate T-cell reconstitution but also induce GVHD, which itself impairs immune reconstitution. We have developed a strategy of alloreactive T-cell depletion, using T-cells expressing the Herpes simplex thymidine kinase (TK) suicide gene combined with a ganciclovir (GCV) treatment. This system permits the selective elimination of dividing TK+ T-cells in vivo. To test this hypothesis in preclinical settings, we have previously developed several experimental models of GVHD using TK+ T-cells in mice. The demonstration that a preventive treatment with GCV administered close to the time of HSCT could control GVHD brought the proof of concept. We now propose a clinical trial to test whether donor lymphocytes infusion (DLI) using TK-transduced cells permits to induce a graft-versus-tumor (GVT) effect for treatment of relapse after HSCT, while GVHD can be controlled by GCV treatment.
Detailed description
DLI-TK is administered either after failure of 1 or several previous standard (std-) DLI of, defined after a minimal follow-up of 2 months after the last injection. To prepare DLI-TK, donor T-cells are transduced with a retroviral vector encoding TK. Transduced cells are selected using a CliniMACS device (MYLTENYI). In case of previous std-DLI received, the DLI-TK cell dose is adjusted to be below or equal to the maximal cell dose previously received in std-DLI. No comparison is planned in the analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| donor lymphocyte infusion | Experimental | Biological: donor lymphocyte infusionDonor T-cell transduction |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Hematological malignancy.
- Previous allogeneic hematopoietic stem cell transplantation.
- Relapse diagnosed at the molecular, cytogenetic, or cytological level.
- Failure of a previous stdILD or inclusion in first intention without previous stdDLI.
- Age > 18 years and < 70 years at the time of inclusion. For patients between 15 and 18 years of age, a case-per case inclusion will be studied.
Key exclusion criteria (3 listed)
- Grade >II acute GVHD or chronic extensive GVHD at the time of inclusion.
- Patient receiving an immunosuppressive treatment for GVHD treatment at the time of inclusion.
- Dysfunction of liver (alanine aminotransferase / aspartate transaminase (ALAT/ASAT) > 5 N, or bilirubin > 50 µM), or of the renal function (creatinine clearance < 30 ml / min).
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 infusionDonor T-cell transduction | Biological | donor lymphocyte infusion |
Primary outcome
Incidence of "severe" GHVD (acute grade >II or chronic extensive) following DLI-TK and treatment with GCV
Time frame: during the 12 months of follow-up
Incidence of "severe" GHVD (acute grade >II or chronic extensive) following DLI-TK and treatment with GCV
3 secondary outcomes
The incidence of GVHD of any grade after DLI-TK
Time frame: during the 12 months of follow-up
The anti-tumoral efficiency of DLI-TK to treat the relapse of the hematological malignancy
Time frame: during the 12 months of follow-up
The survival and the survival without disease after DLI-TK
Time frame: during the 12 months of follow-up
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 14 Jan 2013.
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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.
Sébastien Maury, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
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 infusion in people with Hematological Malignancy, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 10 inclusion and 3 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 14 Jan 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 France. 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?
Incidence of "severe" GHVD (acute grade >II or chronic extensive) following DLI-TK and treatment with GCV (time frame: during the 12 months of follow-up). 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 14 Jan 2013.