Haploidentical Stem Cell TransplantationPhase 1/2NCT01204502
Suicide Gene Therapy Trial
A Phase 1/2 study testing HSVTK retrovirally-transduced donor T lymphocytes in people with Haploidentical Stem Cell Transplantation, run by Great Ormond Street Hospital for Children NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Bone marrow or blood stem cell transplantation is used to treat a wide range of life-threatening conditions. T lymphocytes carried in the graft have powerful beneficial effects and play a vital role in the eradication of leukaemia and in fighting infection, but can also damage healthy tissues and cause… Read more about this study
- Who is it for?
- Ages Up to 16 years
- Conditions the study is for
- Haploidentical Stem Cell Transplantation
- What is being tested?
- HSVTK retrovirally-transduced donor T lymphocytes
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2011to Jan 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 Up to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patients with primary immunodeficiencies, haematological malignancies or metabolic disorders at GOSH (children of both sexes, aged 0 to 16 years) undergoing haploidentical transplant
- Both patient and donor must give informed consent in writing.
- The donor must be willing, able and available for donation of T cells by collection of whole blood or leukapheresis.
- The patient should be free of serious intercurrent illness.
Who cannot join
- Donor unfit or unavailable
- Donor positive for Hepatitis B or C, or HTLV-1, or HIV
- Patient receiving Ganciclovir, Aciclovir, Cidofovir a result of active CMV, adenovirus, varicella zoster or herpes simplex infection infection
- GVHD ≥ grade II before infusion of gene modified T cells
- Serious intercurrent illness
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Great Ormond Street Hospital for Children NHS Trust
London, WC1N 3JH
About this study
Official title: Phase I/II Clinical Trial of T-cell Suicide Gene Therapy Following Haploidentical Stem Cell Transplantation
Bone marrow or blood stem cell transplantation is used to treat a wide range of life-threatening conditions. T lymphocytes carried in the graft have powerful beneficial effects and play a vital role in the eradication of leukaemia and in fighting infection, but can also damage healthy tissues and cause graft-versus-host disease (GVHD).
To safeguard against GVHD, the investigators propose modifying T cells to encode a 'switch' so that they can be eliminated if problems arise.
Children receiving half-matched (haploidentical) transplants from a parent are most likely to benefit from this strategy. At present these patients receive blood stem cells from a parent, but the T cells are removed because the risk of serious GVHD is unacceptable. This means that they are much more likely to suffer from life threatening infections or experience a relapse of leukaemia. The investigators want to use gene therapy to produce "safe" T cells which can be used to strengthen the transplant and prevent these serious complications.
- Conditions
- Haploidentical Stem Cell Transplantation
- Being tested
- HSVTK retrovirally-transduced donor T lymphocytes
- Keywords
- Gene therapy, Haploidentical, Bone marrow transplant, Graft versus host disease, haploidentical stem cell transplantation, T-cell suicide gene therapy
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HSVTK retrovirally-transduced donor T lymphocytesBiological
HSVTK retrovirally-transduced donor T lymphocytes will be given at 1 month intervals, providing that there is no significant GVHD
- dose 1 5x104 cells/kg
- dose 2 5x105 cells/kg
| Study group | Role | What they receive |
|---|---|---|
| HSVTK retrovirally-transduced donor T lymphocytes | Experimental | HSVTK retrovirally-transduced donor T lymphocytes will be given at 1 month intervals, providing that there is no significant GVHD
* dose 1 5x104 cells/kg
* dose 2 5x105 cells/kg Receives: Biological: HSVTK retrovirally-transduced donor T lymphocytes |
What is being measured
The primary outcome is the main question the study is designed to answer.
T-cell reconstitution (as defined by CD4+ cells >300/mm3 & CD3+ cells >500/mm3)
T-cell reconstitution is measured until 12 months after administration of the final dose of gene modified cells
Measured: 12 months after final dose
Secondary outcomes (2)
Incidence of GvHD
Incidence of GvHD is measured until 12 months after administration of the final dose of gene modified cells
Measured: 12 months after final dose
Patient survival
Patient survial is measured until 12 months after administration of the final dose of gene modified cells
Measured: 12 months after final dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2010 (estimated)
- Study startJan 2011
- Primary completionJan 2013
- Study completionJan 2013
Why it stopped: Changes in the clinical practice
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Haploidentical Stem Cell TransplantationStudies 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Great Ormond Street Hospital for Children NHS Foundation Trust
- Sponsor type
- University, hospital or other
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01204502
- Sponsor's protocol ID
- 06MI04
- Status last verified
- Sep 2013
- First submitted
- 16 Sep 2010
- Last updated
- 18 Sep 2013
- Results posted
- No
Publications
Qasim W, Gaspar HB, Thrasher AJ. T cell suicide gene therapy to aid haematopoietic stem cell transplantation. Curr Gene Ther. 2005 Feb;5(1):121-32. doi: 10.2174/1566523052997497.
PubMed 15638716Zhan H, Gilmour K, Chan L, Farzaneh F, McNicol AM, Xu JH, Adams S, Fehse B, Veys P, Thrasher A, Gaspar H, Qasim W. Production and first-in-man use of T cells engineered to express a HSVTK-CD34 sort-suicide gene. PLoS One. 2013 Oct 21;8(10):e77106. doi: 10.1371/journal.pone.0077106. eCollection 2013.
PubMed 24204746
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Clinical Trial of T-cell Suicide Gene Therapy Following Haploidentical Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT01204502
- Acronym / sponsor ID
- 06MI04
- Conditions
- Haploidentical Stem Cell Transplantation
- Keywords
- Gene therapy, Haploidentical, Bone marrow transplant, Graft versus host disease, haploidentical stem cell transplantation, T-cell suicide gene therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Changes in the clinical practice
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Great Ormond Street Hospital for Children NHS Foundation TrustUniversity, hospital or other
- Study start
- Jan 2011
- Primary completion
- Jan 2013 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 17 Sep 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.
Bone marrow or blood stem cell transplantation is used to treat a wide range of life-threatening conditions. T lymphocytes carried in the graft have powerful beneficial effects and play a vital role in the eradication of leukaemia and in fighting infection, but can also damage healthy tissues and cause graft-versus-host disease (GVHD).
To safeguard against GVHD, the investigators propose modifying T cells to encode a 'switch' so that they can be eliminated if problems arise.
Children receiving half-matched (haploidentical) transplants from a parent are most likely to benefit from this strategy. At present these patients receive blood stem cells from a parent, but the T cells are removed because the risk of serious GVHD is unacceptable. This means that they are much more likely to suffer from life threatening infections or experience a relapse of leukaemia. The investigators want to use gene therapy to produce "safe" T cells which can be used to strengthen the transplant and prevent these serious complications.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HSVTK retrovirally-transduced donor T lymphocytes | Experimental | Biological: HSVTK retrovirally-transduced donor T lymphocytesHSVTK retrovirally-transduced donor T lymphocytes will be given at 1 month intervals, providing that there is no significant GVHD * dose 1 5x104 cells/kg * dose 2 5x105 cells/kg |
Who may qualify
- Ages
- Up to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Patients with primary immunodeficiencies, haematological malignancies or metabolic disorders at GOSH (children of both sexes, aged 0 to 16 years) undergoing haploidentical transplant
- Both patient and donor must give informed consent in writing.
- The donor must be willing, able and available for donation of T cells by collection of whole blood or leukapheresis.
- The patient should be free of serious intercurrent illness.
Key exclusion criteria (5 listed)
- Donor unfit or unavailable
- Donor positive for Hepatitis B or C, or HTLV-1, or HIV
- Patient receiving Ganciclovir, Aciclovir, Cidofovir a result of active CMV, adenovirus, varicella zoster or herpes simplex infection infection
- GVHD ≥ grade II before infusion of gene modified T cells
- Serious intercurrent illness
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 |
|---|---|---|
| HSVTK retrovirally-transduced donor T lymphocytesHSVTK retrovirally-transduced donor T lymphocytes will be given at 1 month intervals, providing that there is no significant GVHD * dose 1 5x104 cells/kg * dose 2 5x105 cells/kg | Biological | HSVTK retrovirally-transduced donor T lymphocytes |
Primary outcome
T-cell reconstitution (as defined by CD4+ cells >300/mm3 & CD3+ cells >500/mm3)
Time frame: 12 months after final dose
T-cell reconstitution is measured until 12 months after administration of the final dose of gene modified cells
2 secondary outcomes
Incidence of GvHD
Time frame: 12 months after final dose
Patient survival
Time frame: 12 months after final dose
Results and safety
The study was stopped early (reason given: Changes in the clinical practice). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2013.
- Background: PubMed 15638716Qasim W, Gaspar HB, Thrasher AJ. T cell suicide gene therapy to aid haematopoietic stem cell transplantation. Curr Gene Ther. 2005 Feb;5(1):121-32. doi: 10.2174/1566523052997497.
- Derived from this study: PubMed 24204746Zhan H, Gilmour K, Chan L, Farzaneh F, McNicol AM, Xu JH, Adams S, Fehse B, Veys P, Thrasher A, Gaspar H, Qasim W. Production and first-in-man use of T cells engineered to express a HSVTK-CD34 sort-suicide gene. PLoS One. 2013 Oct 21;8(10):e77106. doi: 10.1371/journal.pone.0077106. eCollection 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.
The record lists no contact. Use the official record to reach the sponsor.
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 HSVTK retrovirally-transduced donor T lymphocytes in people with Haploidentical Stem Cell Transplantation, run by Great Ormond Street Hospital for Children NHS Foundation Trust at 1 site in United Kingdom.
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 5 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: stopped early, as of the sponsor's last update on 18 Sep 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 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 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 was stopped early (reason given: Changes in the clinical practice). Results are not available in the source record.
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?
T-cell reconstitution (as defined by CD4+ cells >300/mm3 & CD3+ cells >500/mm3) (time frame: 12 months after final dose). 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 NCT01204502, which also lists 2 linked publications.
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 Sep 2013.