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

NCT ID: NCT01240525

Last Updated: 2019-02-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

114 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-11-30

Study Completion Date

2019-11-30

Brief Summary

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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

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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.

Conditions

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Graft Versus Host Disease Leukemia Lymphoma Myeloma Myelodysplastic Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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CD4 DLI

Patients will receive trial product manipulated CD4 DLI post transplant as trial treatment.

Group Type OTHER

CD4 DLI

Intervention Type OTHER

Patients will receive CD4 DLI between day 70 to 115 post transplant

No DLI

Patients will receive no DLI post transplant as trial treatment.

Group Type OTHER

No DLI

Intervention Type OTHER

Patients will not receive DLI as trial treatment

Interventions

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CD4 DLI

Patients will receive CD4 DLI between day 70 to 115 post transplant

Intervention Type OTHER

No DLI

Patients will not receive DLI as trial treatment

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

69 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University College, London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ronjon Chakraverty, Professor

Role: PRINCIPAL_INVESTIGATOR

University College Hospital London; UCL Cancer Institute

Locations

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Birmingham Heartlands Hospital

Birmingham, , United Kingdom

Site Status

Bristol Royal Hospital for Children

Bristol, , United Kingdom

Site Status

Addenbrooke's Hospital

Cambridge, , United Kingdom

Site Status

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Site Status

St James's University Hospital

Leeds, , United Kingdom

Site Status

Leicester Royal Infirmary

Leicester, , United Kingdom

Site Status

University College Hospital London (UCLH)

London, , United Kingdom

Site Status

Christie Hospital

Manchester, , United Kingdom

Site Status

Nottingham City Hospital

Nottingham, , United Kingdom

Site Status

Royal Hallamshire Hospital

Sheffield, , United Kingdom

Site Status

University Hospitals Southampton

Southampton, , United Kingdom

Site Status

Countries

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United Kingdom

Related Links

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http://www.ctc.ucl.ac.uk/TrialDetails.aspx?TrialID=54

CRUK \& UCL Cancer Trial Centre - coordinating centre

Other Identifiers

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UCL-10/0241

Identifier Type: OTHER

Identifier Source: secondary_id

LRF-09041

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

EU-21081

Identifier Type: OTHER

Identifier Source: secondary_id

CRUK-UCL-PROT4

Identifier Type: OTHER

Identifier Source: secondary_id

UCL/10/0241

Identifier Type: -

Identifier Source: org_study_id

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