Donor Lymphocyte Infusion After Stem Cell Transplant in Treating Patients With Haematological Cancers (ProT4)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by University College, London
Sponsor:
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT01240525
First received: November 11, 2010
Last updated: October 22, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Graft Versus Host Disease
Leukemia
Lymphoma
Myeloma
Myelodysplastic Syndrome
Other: CD4 DLI
Other: No DLI
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • Progression-free survival at 1 year post-transplant [ Time Frame: during the study and end of study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of patients attaining multi-lineage full donor chimerism in peripheral blood [ Time Frame: End of study ] [ Designated as safety issue: No ]
  • Incidence of infection requiring inpatient treatment [ Time Frame: during the study and end of study ] [ Designated as safety issue: Yes ]
  • Rate of reconstitution of T-cell subsets and viral-specific immunity [ Time Frame: End of study ] [ Designated as safety issue: No ]
  • Cumulative incidence of non-relapse mortality at 1 year [ Time Frame: End of study ] [ Designated as safety issue: No ]
  • Overall survival and non-relapse mortality [ Time Frame: End of study ] [ Designated as safety issue: No ]
  • Incidence, grade, or pattern of graft-versus-host disease [ Time Frame: during the study and end of study ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 86
Study Start Date: November 2011
Estimated Study Completion Date: November 2019
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
CD4 DLI
Patients will receive trial product manipulated CD4 DLI post transplant as trial treatment.
Other: CD4 DLI
Patients will receive CD4 DLI between day 70 to 100 post transplant
No DLI
Patients will receive no DLI post transplant as trial treatment.
Other: No DLI
Patients will not receive DLI as trial treatment

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 Leukaemia & Lymphoma Research (LLR)

  Eligibility

Ages Eligible for Study:   18 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01240525

Contacts
Contact: Ka Man Condne, BSc, MSc 02076799427 ctc.prot4@ucl.ac.uk
Contact: Haematology Trials Group 02076799860 ctc.bnli@ucl.ac.uk

Locations
United Kingdom
Royal Free Hospital Recruiting
London, England, United Kingdom, NW3 2PF
Contact: Contact Person    44-207-679-7513    r.chakraverty@ucl.ac.uk   
Birmingham Heartlands Hospital Recruiting
Birmingham, United Kingdom
Principal Investigator: Richard Lovell, Dr         
Bristol Royal Hospital for Children Not yet recruiting
Bristol, United Kingdom
Principal Investigator: Stephen Robinson, Dr         
Addenbrooke's Hospital Not yet recruiting
Cambridge, United Kingdom
Principal Investigator: Charles Crawley, Dr         
Beatson West of Scotland Cancer Centre Recruiting
Glasgow, Scotland, United Kingdom
Principal Investigator: Andrew Clark, Dr         
St James's University Hospital Not yet recruiting
Leeds, United Kingdom
Principal Investigator: Maria Gilleece, Dr         
Leicester Royal Infirmary Not yet recruiting
Leicester, United Kingdom
Principal Investigator: Ann Hunter, Dr         
University College Hospital London (UCLH) Recruiting
London, United Kingdom
Principal Investigator: Karl Peggs, Dr         
Christie Hospital Recruiting
Manchester, United Kingdom
Principal Investigator: Adrian Bloor, Dr         
Nottingham City Hospital Not yet recruiting
Nottingham, United Kingdom
Principal Investigator: Nigel Russell, Prof         
Royal Hallamshire Hospital Not yet recruiting
Sheffield, United Kingdom
Principal Investigator: John Snowden, Dr         
University Hospitals Southampton Not yet recruiting
Southampton, United Kingdom
Principal Investigator: Debbie Richardson, Dr         
Sponsors and Collaborators
University College, London
Investigators
Principal Investigator: Ronjon Chakraverty, MD Royal Free Hospital; UCL Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT01240525     History of Changes
Other Study ID Numbers: UCL/10/0241, UCL-10/0241, LRF-09041, EU-21081, CRUK-UCL-PROT4
Study First Received: November 11, 2010
Last Updated: October 22, 2012
Health Authority: REC South Central Southampton B: United Kingdom

Keywords provided by University College, London:
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

Additional relevant MeSH terms:
Graft vs Host Disease
Leukemia
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Myelodysplastic Syndromes
Preleukemia
Immune System Diseases
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Precancerous Conditions

ClinicalTrials.gov processed this record on August 26, 2014