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

University College London (UCL)

Status and phase: Unknown; Phase 2

Conditions: Graft Versus Host Disease; Lymphoma; Myeloma; Myelodysplastic Syndrome; Leukemia

Treatments: Other: No DLI; Other: CD4 DLI

Study type: Interventional

Funder types: Other

Identifiers

NCT01240525

UCL-10/0241 (Other Identifier)

CRUK-UCL-PROT4 (Other Identifier)

EU-21081 (Other Identifier)

UCL/10/0241

LRF-09041 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 114 patients

Sex: All

Ages: 18 to 69 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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114 participants in 2 patient groups

CD4 DLI

Other group

Description:

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

Treatment:

Other: CD4 DLI

No DLI

Other group

Description:

Patients will receive no DLI post transplant as trial treatment.

Treatment:

Other: No DLI