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
- 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).
- 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
Peer Reviewed and Funded or Endorsed by Leukaemia & Lymphoma Research (LLR)
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Other : CD4 DLI, Other : No DLI
Study Arm Groups : CD4 DLI, No DLI
See Interventions above
- Progression-free survival at 1 year post-transplant; during the study and 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; 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; Overall survival and non-relapse mortality; End of study; Incidence, grade, or pattern of graft-versus-host disease; during the study and end of study
Sorry, this information is not available
This is available on the Clinicaltrials.gov
18 Years - 69 Years
- 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 the
- fludarabine-melphalan-alemtuzumab conditioning regimen line therapy
- - 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
- - Active acute GvHD
- - Prior grade II-IV GvHD
- - Relapse or progressive disease
- - Primary or secondary graft failure
- - Other cellular therapies
- - Requirement for ongoing immunosuppression
This is in the inclusion criteria above
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
Not available for this trial
Sorry, this information is not available
University College, London