- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01240525
Donor Lymphocyte Infusion After Stem Cell Transplant in Treating Patients With Haematological Cancers (ProT4)
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.
Study Overview
Status
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Birmingham, United Kingdom
- Birmingham Heartlands Hospital
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Bristol, United Kingdom
- Bristol Royal Hospital for Children
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Cambridge, United Kingdom
- Addenbrooke's Hospital
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Glasgow, United Kingdom
- Beatson West of Scotland Cancer Centre
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Leeds, United Kingdom
- St James's University Hospital
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Leicester, United Kingdom
- Leicester Royal Infirmary
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London, United Kingdom
- University College Hospital London (UCLH)
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Manchester, United Kingdom
- Christie Hospital
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Nottingham, United Kingdom
- Nottingham City Hospital
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Sheffield, United Kingdom
- Royal Hallamshire Hospital
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Southampton, United Kingdom
- University Hospitals Southampton
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
At registration (pre-transplant)
Haematological cancer which can be ONE OF the following:
- Non-Hodgkin's lymphoma (NHL) in CR or PR
- Hodgkin's lymphoma (HL) in CR or PR
- Chronic (Pro-)lymphocytic leukaemia (CLL/PLL) in CR or PR
- Plasma cell myeloma (PCM) in CR, VGPR or PR
- Acute myeloid leukaemia (AML) in CR
- Acute lymphoblastic leukaemia (ALL) in CR
- Myelodysplastic syndrome (MDS) < 10% blasts in bone marrow
- Chronic myelomonocytic leukaemia (CMML) < 10% blasts in bone marrow
- Have undergone disease reassessment within 8 weeks prior to registration
HLA-identical sibling transplant to be performed using one of the following reduced intensity alemtuzumab-containing conditioning regimens:
- Fludarabine-busulphan-alemtuzumab
- Fludarabine-melphalan-alemtuzumab
- BCNU-etoposide-cytarabine-melphalan (BEAM)-alemtuzumab
- CCNU-etoposide-cytarabine-melphalan (LEAM)-alemtuzumab
- Aged ≥18 years, and <70 years
- Written informed consent
Exclusion Criteria
- 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
- Prior grade II-IV GvHD
- Relapse or progressive disease
- Primary or secondary graft failure
- Other cellular therapies
- Requirement for ongoing immunosuppression
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: CD4 DLI
Patients will receive trial product manipulated CD4 DLI post transplant as trial treatment.
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Patients will receive CD4 DLI between day 70 to 115 post transplant
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Other: No DLI
Patients will receive no DLI post transplant as trial treatment.
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Patients will not receive DLI as trial treatment
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Progression-free survival at 1 year post-transplant
Time Frame: during the study and end of study
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during the study and end of study
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Proportion of patients attaining multi-lineage full donor chimerism in peripheral blood
Time Frame: End of study
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End of study
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Incidence of infection requiring inpatient treatment
Time Frame: during the study and end of study
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during the study and end of study
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Rate of reconstitution of T-cell subsets and viral-specific immunity
Time Frame: End of study
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End of study
|
Cumulative incidence of non-relapse mortality at 1 year
Time Frame: End of study
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End of study
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Overall survival and non-relapse mortality
Time Frame: End of study
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End of study
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Incidence, grade, or pattern of graft-versus-host disease
Time Frame: during the study and end of study
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during the study and end of study
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Ronjon Chakraverty, Professor, University College Hospital London; UCL Cancer Institute
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- Non-Hodgkin's lymphoma
- Hodgkin's 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
- Myelodysplastic syndrome
- recurrent grade 1 follicular lymphoma
- recurrent grade 2 follicular lymphoma
- recurrent small lymphocytic lymphoma
- stage III small lymphocytic lymphoma
- stage IV small lymphocytic lymphoma
- refractory chronic lymphocytic leukemia
- stage III chronic lymphocytic leukemia
- stage IV chronic lymphocytic leukemia
- graft versus host disease
- Acute myeloid leukaemia
- Chronic (Pro-)lymphocytic leukaemia
- Plasma cell myeloma
- Acute lymphoblastic leukaemia
- Chronic myelomonocytic leukaemia
Additional Relevant MeSH Terms
Other Study ID Numbers
- UCL/10/0241
- UCL-10/0241 (Other Identifier: Sponsor)
- LRF-09041 (Other Grant/Funding Number: Leukaemia & Lymphoma Research)
- EU-21081 (Other Identifier)
- CRUK-UCL-PROT4 (Other Identifier: Cancer Research UK & UCL Cancer Trials Centre)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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