Clinical trial NCT01240525: Donor Lymphocyte Infusion After Stem Cell Transplant in Treating Patients With Haematological Cancers
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
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
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
Myelodysplastic syndrome
Chronic myelomonocytic leukaemia
Lead sponsor: University College, London
Sponsor class: OTHER
First posted: 2010-11-15
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-free survival at 1 year post-transplant
timeFrame: during the study and end of study
Secondary outcomes:
measure: Proportion of patients attaining multi-lineage full donor chimerism in peripheral blood
timeFrame: End of study
measure: Incidence of infection requiring inpatient treatment
timeFrame: during the study and end of study
measure: Rate of reconstitution of T-cell subsets and viral-specific immunity
timeFrame: End of study
measure: Cumulative incidence of non-relapse mortality at 1 year
timeFrame: End of study
measure: Overall survival and non-relapse mortality
timeFrame: End of study
measure: Incidence, grade, or pattern of graft-versus-host disease
timeFrame: during the study and end of study
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: Leeds
country: United Kingdom
facility: St James's University Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: University College Hospital London (UCLH)
city: Manchester
country: United Kingdom
facility: Christie Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
city: Southampton
country: United Kingdom
facility: University Hospitals Southampton
Study officials:
affiliation: University College Hospital London; UCL Cancer Institute
name: Ronjon Chakraverty, Professor
role: PRINCIPAL_INVESTIGATOR
References: