CD8+ Memory T-Cells as Consolidative Therapy After Donor Non-myeloablative Hematopoietic Cell Transplant in Treating Patients With Leukemia or Lymphoma
Condition: Acute Myeloid Leukemia; B-Cell Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Hodgkin Lymphoma; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; T-Cell Non-Hodgkin Lymphoma
MeSH terms: Lymphoma; Leukemia; Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell; Lymphoma, T-Cell; Myelodysplastic Syndromes; Myeloproliferative Disorders
Study type: Interventional
Phase: Phase 2

Summary: 
      This phase 2 trial studies how well cluster of differentiation 8 (CD8)+ memory T-cells work
      as a consolidative therapy following a donor non-myeloablative hematopoietic cell transplant
      in treating patients with leukemia or lymphoma. Giving total lymphoid irradiation and
      anti-thymocyte globulin before a donor hematopoietic cell transplant helps stop the growth of
      cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells.
      When the healthy stem cells from a donor are infused into the patient they may help the
      patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
      Sometimes the transplanted cells from a donor can make an immune response against the body's
      normal cells (called graft-versus-host disease). Giving cyclosporine and mycophenolate
      mofetil after the transplant may stop this from happening. Once the donated stem cells begin
      working, the patient's immune system may see the remaining cancer cells as not belonging in
      the patient's body and destroy them. Giving an infusion of the donor's white blood cells,
      such as CD8+ memory T-cells, may boost this effect and may be an effective treatment to kill
      any cancer cells that may be left in the body (consolidative therapy).
    

Detailed description: 
      Participants undergo total lymphoid irradiation (TLI) on Days -11 to -7 and Days -4 to -1 and
      receive anti-thymocyte globulin (ATG) per standard institutional practice on Days -11 to -7.
      Patients also receive oral cyclosporine daily starting on Day -3, and will continue for at
      least 6 months post-transplant. Patients undergo standard non-myeloablative allogeneic HSCT
      on Day 0. Patients also receive oral mycophenolate mofetil daily beginning on Day 0 and
      continuing until Day 28. Participants receive an intravenous infusion of allogeneic cluster
      of differentiation 8 (CD8)+ memory T-cells over 10 to 20 minutes sometime between day 30 and
      day 60.

      PRIMARY OBJECTIVES:

      I. To determine the rate of conversion to full-donor chimerism (FDC) following a
      post-transplant infusion (Day 30-60) of freshly-enriched allogeneic CD8+ memory T-cells in
      patients with acute myeloid leukemia (AML), non-Hodgkin lymphoma (NHL), chronic lymphocytic
      leukemia (CLL), or Hodgkin lymphoma (HL), who received standard non-myeloablative total
      lymphoid irradiation (TLI) anti-thymocyte globulin (ATG) transplant conditioning.

      SECONDARY OBJECTIVES:

      I. To determine the risk of disease progression, overall and event free survival, and
      non-relapse mortality.

      II. To determine the incidence of acute and chronic graft-versus-host disease (GVHD)
      following the infusion of allogeneic CD8+ memory T-cells.

      OUTLINE:

      Patients undergo TLI on days -11 to -7 and -4 to -1 and receive ATG per standard
      institutional practice on days -11 to -7. Patients also receive cyclosporine orally (PO)
      daily starting on day -3 and will continue for at least 6 months post-transplant. Patients
      undergo non-myeloablative allogeneic hematopoietic stem cell transplant (HSCT) on day 0.
      Patients also receive mycophenolate mofetil PO daily beginning on day 0 and continue until
      day 28. Based on the patient's status after the initial transplant, patients receive CD8+
      memory T-cells intravenously (IV) over 10-20 minutes sometime between day 30 and day 60.

      After completion of study treatment, patients are followed up periodically.
    

Intervention name(s): Anti-Thymocyte Globulin; Cyclosporine; Mycophenolate Mofetil; Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplant; Allogeneic Cluster of Differentiation 8 (CD8)+ Memory T-cells; Total Nodal Irradiation
Intervention type(s): Biological; Drug; Drug; Procedure; Biological; Radiation
Intervention description(s): Given per standard institutional practice; Given PO; Given PO; Undergo nonmyeloablative allogeneic HSCT; Receive CD8+ memory T-cells via IV; Undergo TLI
Other intervention name(s): Antithymocyte Globulin; Antithymocyte Serum; ATG; ATGAM; ATS; Thymoglobulin; 27-400; Ciclosporin; CsA; Cyclosporin; Cyclosporin A; Neoral; OL 27-400; Sandimmun; Sandimmune; SangCya; Cellcept; MMF; Non-myeloablative allogeneic transplant; Nonmyeloablative Stem Cell Transplant; NST; Peripheral Blood Stem Cell (PBSC) Transplant; Peripheral Stem Cell Support; Peripheral Stem Cell Transplant; Allogeneic Lymphocytes; Tumor-Derived Lymphocyte
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Cyclosporins; Thymoglobulin; Antilymphocyte Serum
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Healthy Stem Cell Donor