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

Summary

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

Conditions

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

Interventions

DRUG

Rituximab

Rituximab: 375 mg/m(2)/day intravenous (IV), day 1 (for cluster of differentiation 20 (CD20+) patients).

DRUG

Fludarabine

Fludarabine: 30 mg/m(2)/day intravenous (IV), days -6 to -3.

DRUG

Etoposide

Etoposide: 50 mg/m(2)/day continuous intravenous (CIV), days 1-4.

DRUG

Doxorubicin

Doxorubicin:10 mg/m(2)/day continuous intravenous (CIV), days 1-4.

DRUG

Vincristine

Vincristine: 0.4 mg/m(2)/day continuous intravenous (CIV), days 1-4.

DRUG

Cyclophosphamide

Cyclophosphamide, 300 mg/m(2)/day intravenous (IV), days -6 to -3.

PROCEDURE

Peripheral blood stem cell (PBSC) transplantation

PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell.

GENETIC

T cell donor lymphocyte infusion (DLI) with unmanipulated donor T cells

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).

DRUG

Prednisone

Prednisone: 60 mg/m(2)/day by mouth (PO), days 1-5.

PROCEDURE

Allogeneic hematopoietic stem cell transplant (HSCT)

Allogeneic Hematopoietic Stem Cell Transplant.

DRUG

Filgrastim

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).

GENETIC

T-Rapa cell Donor Lymphocyte Infusion (DLI)

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).

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Steven Z Pavletic, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

11 Years

Max Age

90 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2004-01-01

Primary Completion

2017-07-20

Completion

2017-08-16

FDA Drug

Yes

Countries

• United States

Study Locations