Donor Lymphocyte Infusion After Stem Cell Transplant in Treating Patients With Haematological Cancers

Lymphoma Clinical Trial

— ProT4  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01240525
• Other study ID #: UCL/10/0241
• Secondary ID: UCL-10/0241LRF-0
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 2011
• Est. completion date: November 2019

Study information

• Verified date: February 2019
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 114
• Est. completion date: November 2019
• Est. primary completion date: November 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 69 Years

Eligibility

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

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease
• Leukemia
• Lymphoma
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Myeloma
• Preleukemia

Intervention

Other:
• CD4 DLI
Patients will receive CD4 DLI between day 70 to 115 post transplant
• No DLI
Patients will not receive DLI as trial treatment

Locations

Country	Name	City	State
United Kingdom	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	Christie Hospital	Manchester
United Kingdom	Nottingham City Hospital	Nottingham
United Kingdom	Royal Hallamshire Hospital	Sheffield
United Kingdom	University Hospitals Southampton	Southampton

Sponsors (1)

Lead Sponsor	Collaborator
University College, London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival at 1 year post-transplant		during the study and end of study
Secondary	Proportion of patients attaining multi-lineage full donor chimerism in peripheral blood		End of study
Secondary	Incidence of infection requiring inpatient treatment		during the study and end of study
Secondary	Rate of reconstitution of T-cell subsets and viral-specific immunity		End of study
Secondary	Cumulative incidence of non-relapse mortality at 1 year		End of study
Secondary	Overall survival and non-relapse mortality		End of study
Secondary	Incidence, grade, or pattern of graft-versus-host disease		during the study and end of study

External Links

•   CRUK & UCL Cancer Trial Centre - coordinating centre