Graft Versus Host DiseasePhase 2ProT4NCT01240525
Donor Lymphocyte Infusion After Stem Cell Transplant in Treating Patients With Haematological Cancers
A Phase 2 study testing CD4 DLI and No DLI in people with Graft Versus Host Disease and Leukemia, run by University College, London at 11 sites in United Kingdom.
Trial summary
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and melphalan, before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. Read more about this study
- Who is it for?
- Ages 18 to 69 years
- Conditions the study is for
- Graft Versus Host Disease, Leukemia, Lymphoma
- What is being tested?
- CD4 DLI and No DLI
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 114 participants
- Where
- 11 sitesUnited Kingdom
- Study dates
- Nov 2011to Nov 2019
- Phase
- Phase 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 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Women who are pregnant or breast-feeding
- Life expectancy of <8 weeks
- Currently taking part in any other interventional clinical research study (involving any IMP, ATMP or cellular therapy)
- Organ dysfunction: Creatinine >200μmol/l, Bilirubin >50μmol/l, or AST/ALT > 3x ULN
- Post-transplant
- Active acute GvHD
Show all 11Show fewer
- Prior grade II-IV GvHD
- Relapse or progressive disease
- Primary or secondary graft failure
- Other cellular therapies
- Requirement for ongoing immunosuppression
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United Kingdom11 sites
Birmingham Heartlands Hospital
Birmingham
Bristol Royal Hospital for Children
Bristol
Addenbrooke's Hospital
Cambridge
Beatson West of Scotland Cancer Centre
Glasgow
St James's University Hospital
Leeds
Leicester Royal Infirmary
Leicester
University College Hospital London (UCLH)
London
Christie Hospital
Manchester
Nottingham City Hospital
Nottingham
Royal Hallamshire Hospital
Sheffield
University Hospitals Southampton
Southampton
About this study
Official title: Multicenter Randomized Phase II Study to Evaluate the Efficacy of Prophylactic Transfer of CD4 Lymphocytes After T-cell Depleted Reduced Intensity HLA-Identical Sibling Transplantation for Haematological Cancers
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and melphalan, before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) that have been treated in the laboratory after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving alemtuzumab before transplant and cyclosporine after transplant, may stop this from happening.
PURPOSE: This randomized phase II trial is studying donor lymphocyte infusion after stem cell transplant in preventing cancer relapse or cancer progression in patients with follicular lymphoma, small lymphocytic non-Hodgkin lymphoma, or chronic lymphocytic leukemia.
Read the detailed description
OBJECTIVES:
Primary
- To evaluate the effect of prophylactic transfer of donor CD4 cells after T-cell depleted reduced-intensity HLA-identical sibling transplantation upon the risk of relapse or progression in patients with haematological cancers (e.g. NHL, HL, CLL/PLL, PCM, AML, ALL, MDS or CMML depending on the disease status).
Secondary
- To evaluate the effect of prophylactic transfer of donor CD4 cells upon the risk of graft-versus-host disease (GvHD) in these patients.
- To evaluate the effect of prophylactic transfer of donor CD4 cells upon the rates of conversion to full donor chimerism in peripheral blood in these patients.
- To determine the effect of prophylactic transfer of donor CD4 cells upon immune reconstitution in these patients.
- To evaluate the impact of prophylactic transfer of donor CD4 cells upon non-relapse mortality and overall survival of these patients.
OUTLINE: This is a multicenter study.
Patients receive fludarabine IV, melphalan IV, and alemtuzumab IV as reduced intensity conditioning for T-cell depletion followed by a reduced-intensity HLA-identical sibling stem cell transplantation on day 0. Withdrawal of cyclosporine immunosuppression therapy commence at day 40 with tapering over a period of 3-4 weeks, according to the discretion of the PI. Patients are reassessed between day 70-90 post-transplantation. Patients with stable engraftment, no significant graft-versus-host disease, and no early relapse or progression are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive an allogeneic CD4 donor lymphocyte infusion (DLI) at a dose of 1 x10^6 CD4 cells/kg body weight without any other medication once between day 100-120.
- Arm II: Patients receive no further treatment.
Patients undergo blood sample collection for chimerism studies and translational research.
After completion of study treatment, patients are followed up periodically for 1 years and then annually.
Peer Reviewed and Funded or Endorsed by Bloodwise.
- Conditions
- Graft Versus Host Disease, Leukemia, Lymphoma, Myeloma, Myelodysplastic Syndrome
- Being tested
- CD4 DLI, No DLI
- Keywords
- graft versus host disease, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, Waldenstrom macroglobulinemia, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, refractory chronic lymphocytic leukemia, Non-Hodgkin's lymphoma, Hodgkin's lymphoma, Chronic (Pro-)lymphocytic leukaemia, Plasma cell myeloma, Acute myeloid leukaemia, Acute lymphoblastic leukaemia
- Medical subject headings
- Graft vs Host Disease, Leukemia, Lymphoma, Neoplasms, Plasma Cell, Myelodysplastic Syndromes, Lymphoma, Follicular, Leukemia, Lymphocytic, Chronic, B-Cell, Waldenstrom Macroglobulinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD4 DLIOther
Patients will receive CD4 DLI between day 70 to 115 post transplant
No DLIOther
Patients will not receive DLI as trial treatment
| Study group | Role | What they receive |
|---|---|---|
| CD4 DLI | Other | Patients will receive trial product manipulated CD4 DLI post transplant as trial treatment. Receives: Other: CD4 DLI |
| No DLI | Other | Patients will receive no DLI post transplant as trial treatment. Receives: Other: No DLI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival at 1 year post-transplant
Measured: during the study and end of study
Secondary outcomes (6)
Proportion of patients attaining multi-lineage full donor chimerism in peripheral blood
Measured: End of study
Incidence of infection requiring inpatient treatment
Measured: during the study and end of study
Rate of reconstitution of T-cell subsets and viral-specific immunity
Measured: End of study
Cumulative incidence of non-relapse mortality at 1 year
Measured: End of study
Overall survival and non-relapse mortality
Measured: End of study
Incidence, grade, or pattern of graft-versus-host disease
Measured: during the study and end of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2010 (estimated)
- Study startNov 2011
- Primary completionNov 2019 (estimated)
- Study completionNov 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by University College, LondonThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 114 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ronjon Chakraverty, Professor, Principal investigator, University College Hospital London; UCL Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01240525
- Sponsor's protocol ID
- UCL/10/0241
- Other IDs
- UCL-10/0241, LRF-09041, EU-21081, CRUK-UCL-PROT4
- Acronym
- ProT4
- Status last verified
- Feb 2019
- First submitted
- 11 Nov 2010
- Last updated
- 12 Feb 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Randomized Phase II Study to Evaluate the Efficacy of Prophylactic Transfer of CD4 Lymphocytes After T-cell Depleted Reduced Intensity HLA-Identical Sibling Transplantation for Haematological Cancers
- ClinicalTrials.gov ID
- NCT01240525
- Acronym / sponsor ID
- ProT4 / UCL/10/0241
- Conditions
- Graft Versus Host Disease, Leukemia, Lymphoma, Myeloma, Myelodysplastic Syndrome
- Keywords
- graft versus host disease, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, Waldenstrom macroglobulinemia, stage III grade 1 follicular lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 114 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Study start
- Nov 2011 (actual)
- Primary completion
- Nov 2019 (estimated)
- Study completion
- Nov 2019 (estimated)
- First posted
- 15 Nov 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.
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and melphalan, before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) that have been treated in the laboratory after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving alemtuzumab before transplant and cyclosporine after transplant, may stop this from happening.
PURPOSE: This randomized phase II trial is studying donor lymphocyte infusion after stem cell transplant in preventing cancer relapse or cancer progression in patients with follicular lymphoma, small lymphocytic non-Hodgkin lymphoma, or chronic lymphocytic leukemia.
Detailed description
OBJECTIVES:
Primary
- To evaluate the effect of prophylactic transfer of donor CD4 cells after T-cell depleted reduced-intensity HLA-identical sibling transplantation upon the risk of relapse or progression in patients with haematological cancers (e.g. NHL, HL, CLL/PLL, PCM, AML, ALL, MDS or CMML depending on the disease status).
Secondary
- To evaluate the effect of prophylactic transfer of donor CD4 cells upon the risk of graft-versus-host disease (GvHD) in these patients.
- To evaluate the effect of prophylactic transfer of donor CD4 cells upon the rates of conversion to full donor chimerism in peripheral blood in these patients.
- To determine the effect of prophylactic transfer of donor CD4 cells upon immune reconstitution in these patients.
- To evaluate the impact of prophylactic transfer of donor CD4 cells upon non-relapse mortality and overall survival of these patients.
OUTLINE: This is a multicenter study.
Patients receive fludarabine IV, melphalan IV, and alemtuzumab IV as reduced intensity conditioning for T-cell depletion followed by a reduced-intensity HLA-identical sibling stem cell transplantation on day 0. Withdrawal of cyclosporine immunosuppression therapy commence at day 40 with tapering over a period of 3-4 weeks, according to the discretion of the PI. Patients are reassessed between day 70-90 post-transplantation. Patients with stable engraftment, no significant graft-versus-host disease, and no early relapse or progression are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive an allogeneic CD4 donor lymphocyte infusion (DLI) at a dose of 1 x10^6 CD4 cells/kg body weight without any other medication once between day 100-120.
- Arm II: Patients receive no further treatment.
Patients undergo blood sample collection for chimerism studies and translational research.
After completion of study treatment, patients are followed up periodically for 1 years and then annually.
Peer Reviewed and Funded or Endorsed by Bloodwise.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CD4 DLI | Other | Other: CD4 DLIPatients will receive trial product manipulated CD4 DLI post transplant as trial treatment. |
| No DLI | Other | Other: No DLIPatients will receive no DLI post transplant as trial treatment. |
Who may qualify
- Ages
- 18 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (11 listed)
- Women who are pregnant or breast-feeding
- Life expectancy of <8 weeks
- Currently taking part in any other interventional clinical research study (involving any IMP, ATMP or cellular therapy)
- Organ dysfunction: Creatinine >200μmol/l, Bilirubin >50μmol/l, or AST/ALT > 3x ULN
- Post-transplant
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 |
|---|---|---|
| CD4 DLIPatients will receive CD4 DLI between day 70 to 115 post transplant | Other | CD4 DLI |
| No DLIPatients will not receive DLI as trial treatment | Other | No DLI |
Primary outcome
Progression-free survival at 1 year post-transplant
Time frame: during the study and end of study
6 secondary outcomes
Proportion of patients attaining multi-lineage full donor chimerism in peripheral blood
Time frame: End of study
Incidence of infection requiring inpatient treatment
Time frame: during the study and end of study
Rate of reconstitution of T-cell subsets and viral-specific immunity
Time frame: End of study
Cumulative incidence of non-relapse mortality at 1 year
Time frame: End of study
Overall survival and non-relapse mortality
Time frame: End of study
Incidence, grade, or pattern of graft-versus-host disease
Time frame: during the study and end of study
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2019.
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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.
Ronjon Chakraverty, Professor principal investigator
University College Hospital London; UCL Cancer Institute
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CD4 DLI and No DLI in people with Graft Versus Host Disease and Leukemia, run by University College, London at 11 sites 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 0 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 12 Feb 2019. 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 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?
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?
Progression-free survival at 1 year post-transplant (time frame: during the study and end of study). 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 Feb 2019.