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

Primary Purpose

Graft Versus Host Disease, Leukemia, Lymphoma

Status
Unknown status
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
CD4 DLI
No DLI
Sponsored by
University College, London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Graft Versus Host Disease focused on measuring 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

Eligibility Criteria

18 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Birmingham Heartlands Hospital
  • Bristol Royal Hospital for Children
  • Addenbrooke's Hospital
  • Beatson West of Scotland Cancer Centre
  • St James's University Hospital
  • Leicester Royal Infirmary
  • University College Hospital London (UCLH)
  • Christie Hospital
  • Nottingham City Hospital
  • Royal Hallamshire Hospital
  • University Hospitals Southampton

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

CD4 DLI

No DLI

Arm Description

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

Patients will receive no DLI post transplant as trial treatment.

Outcomes

Primary Outcome Measures

Progression-free survival at 1 year post-transplant

Secondary Outcome Measures

Proportion of patients attaining multi-lineage full donor chimerism in peripheral blood
Incidence of infection requiring inpatient treatment
Rate of reconstitution of T-cell subsets and viral-specific immunity
Cumulative incidence of non-relapse mortality at 1 year
Overall survival and non-relapse mortality
Incidence, grade, or pattern of graft-versus-host disease

Full Information

First Posted
November 11, 2010
Last Updated
February 11, 2019
Sponsor
University College, London
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1. Study Identification

Unique Protocol Identification Number
NCT01240525
Brief Title
Donor Lymphocyte Infusion After Stem Cell Transplant in Treating Patients With Haematological Cancers
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Unknown status
Study Start Date
November 2011 (Actual)
Primary Completion Date
November 2019 (Anticipated)
Study Completion Date
November 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University College, London

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
114 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CD4 DLI
Arm Type
Other
Arm Description
Patients will receive trial product manipulated CD4 DLI post transplant as trial treatment.
Arm Title
No DLI
Arm Type
Other
Arm Description
Patients will receive no DLI post transplant as trial treatment.
Intervention Type
Other
Intervention Name(s)
CD4 DLI
Intervention Description
Patients will receive CD4 DLI between day 70 to 115 post transplant
Intervention Type
Other
Intervention Name(s)
No DLI
Intervention Description
Patients will not receive DLI as trial treatment
Primary Outcome Measure Information:
Title
Progression-free survival at 1 year post-transplant
Time Frame
during the study and end of study
Secondary Outcome Measure Information:
Title
Proportion of patients attaining multi-lineage full donor chimerism in peripheral blood
Time Frame
End of study
Title
Incidence of infection requiring inpatient treatment
Time Frame
during the study and end of study
Title
Rate of reconstitution of T-cell subsets and viral-specific immunity
Time Frame
End of study
Title
Cumulative incidence of non-relapse mortality at 1 year
Time Frame
End of study
Title
Overall survival and non-relapse mortality
Time Frame
End of study
Title
Incidence, grade, or pattern of graft-versus-host disease
Time Frame
during the study and end of study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ronjon Chakraverty, Professor
Organizational Affiliation
University College Hospital London; UCL Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Birmingham Heartlands Hospital
City
Birmingham
Country
United Kingdom
Facility Name
Bristol Royal Hospital for Children
City
Bristol
Country
United Kingdom
Facility Name
Addenbrooke's Hospital
City
Cambridge
Country
United Kingdom
Facility Name
Beatson West of Scotland Cancer Centre
City
Glasgow
Country
United Kingdom
Facility Name
St James's University Hospital
City
Leeds
Country
United Kingdom
Facility Name
Leicester Royal Infirmary
City
Leicester
Country
United Kingdom
Facility Name
University College Hospital London (UCLH)
City
London
Country
United Kingdom
Facility Name
Christie Hospital
City
Manchester
Country
United Kingdom
Facility Name
Nottingham City Hospital
City
Nottingham
Country
United Kingdom
Facility Name
Royal Hallamshire Hospital
City
Sheffield
Country
United Kingdom
Facility Name
University Hospitals Southampton
City
Southampton
Country
United Kingdom

12. IPD Sharing Statement

Links:
URL
http://www.ctc.ucl.ac.uk/TrialDetails.aspx?TrialID=54
Description
CRUK & UCL Cancer Trial Centre - coordinating centre

Learn more about this trial

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

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