Donor Lymphocyte Infusion After Stem Cell Transplant in Treating Patients With Haematological Cancers
- Conditions
- LymphomaGraft Versus Host DiseaseLeukemiaMyelomaMyelodysplastic Syndrome
- Interventions
- Other: No DLIOther: CD4 DLI
- Registration Number
- NCT01240525
- Lead Sponsor
- University College, London
- Brief 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. 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 114
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description No DLI No DLI Patients will receive no DLI post transplant as trial treatment. CD4 DLI CD4 DLI Patients will receive trial product manipulated CD4 DLI post transplant as trial treatment.
- Primary Outcome Measures
Name Time Method Progression-free survival at 1 year post-transplant during the study and end of study
- Secondary Outcome Measures
Name Time Method Incidence, grade, or pattern of graft-versus-host disease during the study and end of study Rate of reconstitution of T-cell subsets and viral-specific immunity End of study Cumulative incidence of non-relapse mortality at 1 year End of study Proportion of patients attaining multi-lineage full donor chimerism in peripheral blood End of study Incidence of infection requiring inpatient treatment during the study and end of study Overall survival and non-relapse mortality End of study
Trial Locations
- Locations (11)
Birmingham Heartlands Hospital
🇬🇧Birmingham, United Kingdom
Bristol Royal Hospital for Children
🇬🇧Bristol, United Kingdom
Addenbrooke's Hospital
🇬🇧Cambridge, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
St James's University Hospital
🇬🇧Leeds, United Kingdom
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
University College Hospital London (UCLH)
🇬🇧London, United Kingdom
Royal Hallamshire Hospital
🇬🇧Sheffield, United Kingdom
Nottingham City Hospital
🇬🇧Nottingham, United Kingdom
University Hospitals Southampton
🇬🇧Southampton, United Kingdom
Christie Hospital
🇬🇧Manchester, United Kingdom