Donor Stem Cell Transplant With No or Low-Intensity Chemotherapy Using Sirolimus and Treated Immune Cells to Treat Blood and Lymph Cancers

Part of paid clinical trials in Bethesda, Maryland.

Sponsor
National Cancer Institute (NCI)
Study ID
NCT00074490
Phase
PHASE2
Status
Terminated

Conditions

  • Leukemia
  • Lymphoma
  • Multiple Myleoma
  • Myelodysplastic Syndrome
  • Myeloproliferative Disorders

Eligibility Criteria

Sex
ALL
Age
11 Years - 90 Years
Healthy Volunteers
Accepted

Interventions

  • Rituximab — DRUG
    Rituximab: 375 mg/m(2)/day intravenous (IV), day 1 (for cluster of differentiation 20 (CD20+) patients).
  • Fludarabine — DRUG
    Fludarabine: 30 mg/m(2)/day intravenous (IV), days -6 to -3.
  • Etoposide — DRUG
    Etoposide: 50 mg/m(2)/day continuous intravenous (CIV), days 1-4.
  • Doxorubicin — DRUG
    Doxorubicin:10 mg/m(2)/day continuous intravenous (CIV), days 1-4.
  • Vincristine — DRUG
    Vincristine: 0.4 mg/m(2)/day continuous intravenous (CIV), days 1-4.
  • Cyclophosphamide — DRUG
    Cyclophosphamide, 300 mg/m(2)/day intravenous (IV), days -6 to -3.
  • Peripheral blood stem cell (PBSC) transplantation — PROCEDURE
    PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell.
  • T cell donor lymphocyte infusion (DLI) with unmanipulated donor T cells — GENETIC
    The dose of the T cells will attempt to be held constant for each study recipient (target dose 2.5 x 10(7) T cells/kg; minimum dose will be 1 x 10(7) T cells/kg).
  • Prednisone — DRUG
    Prednisone: 60 mg/m(2)/day by mouth (PO), days 1-5.
  • Allogeneic hematopoietic stem cell transplant (HSCT) — PROCEDURE
    Allogeneic Hematopoietic Stem Cell Transplant.
  • Filgrastim — DRUG
    Filgrastim: 5 mcg/kg/day subcutaneous (SC), day 6 (require absolute neutrophil count (ANC) \> 1000, two values; or ANC \> 5000 cells/ul on one occasion).
  • T-Rapa cell Donor Lymphocyte Infusion (DLI) — GENETIC
    The dose of T helper 2 (Th2) cells or unmanipulated donor T cells will attempt to be held constant for each study recipient (target dose 2.5 x 10(7) Th2/kg; minimum dose will be 1 x 10(7) Th2/kg).

Study Details

Background: Patients with cancers of the blood and immune system often benefit from transplants of stem cells from a genetically well-matched sibling. However, severe problems may follow these transplants because of the high-dose chemotherapy and radiation that accompany the procedure. Also, donated immune cells sometimes attack healthy tissues in a reaction called graft-versus-host disease (GVHD), damaging organs such as the liver, intestines and skin. To reduce toxicity of high-dose preparative chemotherapy, this study performs allogeneic transplant after low doses of chemotherapy. In an attempt to improve anti-tumor effects without increasing GVHD, this study uses donor immune cells (T helper 2 (Th2) cells) grown in the laboratory; some patients will receive standard donor immune cells (not grown in laboratory). All patients will receive immune modulating drugs sirolimus and cyclosporine to prevent GVHD. Objective: To determine the safety, treatment effects and rate of GVHD in patients receiving transplants that use low-intensity chemotherapy, sirolimus plus cyclosporine, and transplant booster with either Th2 cells or standard immune cells. Eligibility: Patients 16 to 75 years of age with acute or chronic leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma, or myelodysplastic syndrome. Patients must have a suitable genetically matched sibling donor and adequate kidney, heart and lung function. Design: The protocol has three treatment groups: cohort 1, Th2 booster at two weeks post-transplant; cohort 2, standard T cell booster at two weeks post-transplant; cohort 3, multiple infusion of Th2 cells. Condition: Hematologic Neoplasms, Myeloproliferative Disorders Intervention: Biological; therapeutic allogeneic lymphocytes Drug: Sirolimus Study Type: Interventional Study Design: Primary Purpose: Treatment Phase: Phase II

Key Dates

Start date
Jan 1, 2004
Status verified
Dec 2018
Primary completion
Jul 20, 2017
Completion
Aug 16, 2017

Study Design

Enrollment
442 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Arm IVD cohort 1 (Th2 DLI)
    Patients receive low intensity fludarabine phosphate intravenous (IV) and cyclophosphamide IV on days -6 to -3. Patients undergo donor lymphocyte infusion (DLI) with sirolimus generated donor T-helper 2 (Th2) cells on day 14 (single T-Rapa cell DLI in patients with cluster of differentiation 4 (CD4) count between 100 and 200 inclusive)
  • Experimental: Arm IVD cohort 2 (conventional DLI)
    Patients receive low intensity fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3. Patients undergo DLI with unmanipulated donor T-cells on day 14 (single T- cell DLI in patients with low CD4 count between 100 and 200 inclusive)
  • Experimental: Arm IVD cohort 3 (multiple Th2 DLI)
    Patients with nonlymphoma diagnosis or rapidly progressive lymphoma undergo DLI with multiple infusions of sirolimus generated donor Th2 cells beginning on day 14 (multiple T-Rapa cell DLI in patients with CD4 count lower than 100 or ALC lower than 300)
  • Experimental: Arm IVA (12-day expanded Th2 DLI)
    Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine by mouth twice a day (PO BID) on days -4 to 100, and standard dose sirolimus PO on days -2 to 14. Patients undergo mobilized allogeneic peripheral blood stem cells (PBSC) on day 0. Patients undergo DLI with 12-day expanded sirolimus-generated donor Th2 cells on day 14.
  • Experimental: Arm IVB (6-day expanded Th2 DLI)
    Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine PO BID on days -4 to 100, and standard dose sirolimus PO on days -2 to 14. Patients undergo mobilized allogeneic PBSC or bone marrow transplant on day 0. Patients undergo DLI with 6-day expanded sirolimus-generated donor Th2 cells on day 14.
  • Experimental: Arm IVC (6-day expanded Th2 DLI and High-Dose Sirolimus)
    Patients receive low-intensity preparative chemotherapy with fludarabine phosphate IV and cyclophosphamide IV on days -6 to -3, cyclosporine PO BID on days -7 to 100 and high dose sirolimus PO on days -4 to 7, Patients undergo mobilized allogeneic PBSC on day 0. Patients undergo DLI with 6-day expanded sirolimus-generated donor Th2 cells on day 14.

Primary Outcome Measure

Percentage of Patients to Receive T Cell Infusion [ Time Frame: first 100 days post-transplant ]

Locations (2)

FacilityCityStateZIPSite coordinators
National Institutes of Health Clinical Center, 9000 Rockville PikeBethesdaMaryland20892-
Hackensack University Medical CenterHackensackNew Jersey07601-

Find similar trials in Bethesda, MD

By condition
Leukemia (other)
By specialty
OncologyBlood cancer
By research site
National Institutes of Health Clinical Center, 9000 Rockville Pike· Bethesda, MDHackensack University Medical Center· Hackensack, NJ

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