Stem Cell Transplantation in Patients With High-Risk and Recurrent Pediatric Sarcomas

Summary

This study will examine the safety and effectiveness of stem cell transplantation for treating patients with sarcomas (tumors of the bone, nerves, or soft tissue). Stem cells are immature cells in the bone marrow and blood stream that develop into blood cells. Stem cells transplanted from a healthy donor travel to the patient's bone marrow and begin producing normal cells. In patients with certain cancers, such as leukemia and lymphoma, the donor's immune cells attack the patient's cancer cells in what is called a "graft-versus-tumor" effect, contributing to cure of the disease. This study will determine whether this treatment can be used successfully to treat patients with sarcomas.

Patients between 4 and 35 years of age with a sarcoma that has spread from the primary site or cannot be removed surgically, and for whom effective treatment is not available, may be eligible for this study. Candidates must have been diagnosed by the age of 30 at the time of enrollment. They must have a matched donor (usually a sibling). Participants undergo the following procedures:

Donors: Stem cells are collected from the donor. To do this, the hormone granulocyte colony stimulating factor (G-CSF) is injected under the skin for several days to move stem cells out of the bone marrow into the bloodstream. Then, the cells are collected by apheresis. In this procedure the blood is drawn through a needle placed in one arm and pumped into a machine where the stem cells are separated out and removed. The rest of the blood is returned to the donor through a needle in the other arm.

Patients: For patients who do not already have a central venous catheter (plastic tube), one is placed into a major vein. This tube can stay in the body the entire treatment period for giving medications, transfusing blood, , withdrawing blood samples, and delivering the donated stem cells. Before the transplant procedure, patients receive from one to three cycles of "induction" chemotherapy, with each cycle consisting of 5 days of fludarabine, cyclophosphamide, etoposide, doxorubicin, vincristine, and prednisone followed by at least a 17-day rest period. All the drugs are infused through the catheter except prednisone, which is taken by mouth. After the induction therapy, the patient is admitted to the hospital for 5 days of chemotherapy with high doses of cyclophosphamide, melphalan, and fludarabine. Two days later, the stem cells are infused. The anticipated hospital stay is about 3 weeks, but may be longer if complications arise. Patients are discharged when their white cell count is near normal, they have no fever or infection, they can take sufficient food and fluids by mouth, and they have no signs of serious graft-versus-host disease (GVHD)-a condition in which the donor's cells "see" the patient's cells as foreign and mount an immune response against them.

After hospital discharge, patients are followed in the clinic at least once or twice weekly for a medical history, physical exam, and blood tests for 100 days. They receive medications to prevent infection and GVHD and, if needed, blood transfusions. If GVHD has not developed by about 120 days post transplant, patients receive additional white cells to boost the immune response. After 100 days, follow-up visits may be less frequent. Follow-up continues for at least 5 years. During the course of the study, patients undergo repeated medical evaluations, including blood tests and radiology studies, to check on the cancer and on any treatment side effects. On four occasions, white blood cells may be collected through apheresis to see if immune responses can be generated against the sarcomas treated in this study. Positron emission tomography (PET) scans may be done on five occasions. This test uses a radioactive material to produce images useful in detecting primary tumors and cancer that has spread.

Conditions

• Sarcoma

Interventions

DRUG

F-18 Fluorodeoxyglucose

BIOLOGICAL

therapeutic allogeneic lymphocytes

Lymphocyte cells are collected from a healthy donor by apheresis and infused into the patient with a central venous catheter.

DRUG

cyclophosphamide

Induction - 750 mg/m\^2 intravenous (IV) infusion over 30 minutes x 1 dose. Day 5. Transplant - 1200 mg/m\^2 per day IV infusion over 2 hours daily for 4 days; days -6, -5, -4, -3.

DRUG

cyclosporine

6 mg/kg per dose orally every other day (no day 9 dose).

DRUG

doxorubicin hydrochloride

Induction - 10 mg/m\^2 per day continuous intravenous (IV) infusion over 24 hours daily for 4 days. Days 1, 2, 3, 4.

DRUG

etoposide

50 mg/m\^2 per day continuous intravenous (IV) infusion over 24 hours daily for 4 days. Days 1, 2, 3, 4.

DRUG

fludarabine phosphate

Induction - 25 mg/m\^2 per day intravenous (IV) infusion over 30 minutes daily for 3 days. Days 1, 2, 3. Transplant - 30 mg/m\^2 per day IV infusion over 30 minutes daily for 4 days; days -6, -5, -4, -3.

DRUG

melphalan

Transplant - 100 mg/m\^2 per day intravenous (IV) infusion over 15 minutes for 1 day; day -2.

DRUG

prednisone

Induction - 60 mg/m\^2 per day in 2-4 divided doses by mouth daily for 5 days; days 1, 2, 3, 4, 5.

DRUG

sirolimus

Initiated on day +3. Patients \>40kg, the initial dose will be 2 mg every 24 hours orally. Patients \<40 kg, the initial dose will be 1 mg/m\^2.

DRUG

tacrolimus

Day -1 at least 24 hours before the stem cell infusion at a dose of 0.03 mg/kg/day as a continuous infusion. Twelve hours later oral dose initiated at a dose of 0.1-0.15 mg/kg/day in two divided doses every 12 hours.

DRUG

vincristine sulfate

Induction - 0.4 mg/m\^2 per day continuous intravenous (IV) infusion over 24 hours daily for 4 days; 1, 2, 3, 4.

PROCEDURE

peripheral blood stem cell transplantation

Stem cells from a healthy donor are collected and transplanted into the patient using a central venous catheter.

DRUG

Filgrastim

PROCEDURE

Peripheral Blood Stem Cell donation

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Terry Fry, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

5 Years

Max Age

35 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2002-09-19

Primary Completion

2009-05-01

Completion

2011-12-14

Countries

• United States

Study Locations