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

This study is currently recruiting participants.
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

November 11, 2010
October 22, 2012
November 2011
November 2015   (final data collection date for primary outcome measure)
Progression-free survival at 1 year post-transplant [ Time Frame: during the study and end of study ] [ Designated as safety issue: No ]
Progression-free survival at 1 year [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01240525 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Incidence, grade, or pattern of graft-versus-host disease [ Designated as safety issue: Yes ]
  • Proportion of patients attaining multi-lineage full donor chimerism in peripheral blood [ Designated as safety issue: No ]
  • Incidence of infection requiring inpatient treatment [ Designated as safety issue: Yes ]
  • Rate of reconstitution of T-cell subsets and viral-specific immunity [ Designated as safety issue: No ]
  • Proportion of patients with detectable minimal residual disease [ Designated as safety issue: No ]
  • Cumulative incidence of non-relapse mortality at 1 year [ Designated as safety issue: No ]
  • Overall survival and non-relapse mortality [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Donor Lymphocyte Infusion After Stem Cell Transplant in Treating Patients With Haematological Cancers
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

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.

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)

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Graft Versus Host Disease
  • Leukemia
  • Lymphoma
  • Myeloma
  • Myelodysplastic Syndrome
  • Other: CD4 DLI
    Patients will receive CD4 DLI between day 70 to 100 post transplant
  • Other: No DLI
    Patients will not receive DLI as trial treatment
  • CD4 DLI
    Patients will receive trial product manipulated CD4 DLI post transplant as trial treatment.
    Intervention: Other: CD4 DLI
  • No DLI
    Patients will receive no DLI post transplant as trial treatment.
    Intervention: Other: No DLI
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
86
November 2019
November 2015   (final data collection date for primary outcome measure)

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
Both
18 Years to 69 Years
No
Contact: Ka Man Condne, BSc, MSc 02076799427 ctc.prot4@ucl.ac.uk
Contact: Haematology Trials Group 02076799860 ctc.bnli@ucl.ac.uk
United Kingdom
 
NCT01240525
UCL/10/0241, UCL-10/0241, LRF-09041, EU-21081, CRUK-UCL-PROT4
Yes
University College, London
University College, London
Not Provided
Principal Investigator: Ronjon Chakraverty, MD Royal Free Hospital; UCL Cancer Institute
University College, London
October 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP