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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01240525
Recruitment Status : Active, not recruiting
First Posted : November 15, 2010
Last Update Posted : February 12, 2019
Information provided by (Responsible Party):
University College, London

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.

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

Detailed Description:



  • 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 then annually.

Peer Reviewed and Funded or Endorsed by Bloodwise.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 114 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Actual Study Start Date : November 2011
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : November 2019

Arm Intervention/treatment
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 115 post transplant

Patients will receive no DLI post transplant as trial treatment.
Other: No DLI
Patients will not receive DLI as trial treatment

Primary Outcome Measures :
  1. Progression-free survival at 1 year post-transplant [ Time Frame: during the study and end of study ]

Secondary Outcome Measures :
  1. Proportion of patients attaining multi-lineage full donor chimerism in peripheral blood [ Time Frame: End of study ]
  2. Incidence of infection requiring inpatient treatment [ Time Frame: during the study and end of study ]
  3. Rate of reconstitution of T-cell subsets and viral-specific immunity [ Time Frame: End of study ]
  4. Cumulative incidence of non-relapse mortality at 1 year [ Time Frame: End of study ]
  5. Overall survival and non-relapse mortality [ Time Frame: End of study ]
  6. Incidence, grade, or pattern of graft-versus-host disease [ Time Frame: during the study and end of study ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 69 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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


  • Active acute GvHD
  • Prior grade II-IV GvHD
  • Relapse or progressive disease
  • Primary or secondary graft failure
  • Other cellular therapies
  • Requirement for ongoing immunosuppression

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01240525

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, United Kingdom
Sponsors and Collaborators
University College, London
Principal Investigator: Ronjon Chakraverty, Professor University College Hospital London; UCL Cancer Institute

Additional Information:
Responsible Party: University College, London Identifier: NCT01240525     History of Changes
Other Study ID Numbers: UCL/10/0241
UCL-10/0241 ( Other Identifier: Sponsor )
LRF-09041 ( Other Grant/Funding Number: Leukaemia & Lymphoma Research )
EU-21081 ( Other Identifier )
CRUK-UCL-PROT4 ( Other Identifier: Cancer Research UK & UCL Cancer Trials Centre )
First Posted: November 15, 2010    Key Record Dates
Last Update Posted: February 12, 2019
Last Verified: February 2019

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:
Myelodysplastic Syndromes
Graft vs Host Disease
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions