Phase 2 N=60 Treatment

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

Sarcoma

Bottom Line

View on ClinicalTrials.gov: NCT00043979 ↗

Enrolled (actual)

Serious AEs

96.7%

Results posted

Sep 2013

Primary outcome: Primary: Number of Participants With Engraftment — 23 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: F-18 Fluorodeoxyglucose (Drug); therapeutic allogeneic lymphocytes (Biological); cyclophosphamide (Drug); cyclosporine (Drug); doxorubicin hydrochloride (Drug); etoposide (Drug); fludarabine phosphate (Drug); melphalan (Drug); prednisone (Drug); sirolimus (Drug); tacrolimus (Drug); vincristine sulfate (Drug); peripheral blood stem cell transplantation (Procedure); Filgrastim (Drug); Peripheral Blood Stem Cell donation (Procedure)
Age: Pediatric, Adult · 5+ yrs
Sex: All
Sponsor: National Cancer Institute (NCI)
Primary completion: May 2009

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With Engraftment	23	—
PRIMARY Toxicity	30	—
SECONDARY Number of Participants With Acute and Chronic GVHD	12; 5; 12; 5	—
SECONDARY Median Time to Reach Absolute Neutrophil Count of 500/mm(3)	9	—
SECONDARY Median Time to Reach a Platelet Count of 50,000/mm(3)	15	—
SECONDARY Early Post Transplantation Relapse	100	—
SECONDARY Median Progression Free Survival	15.9	—
SECONDARY Two Year Survival Rate for Patients Undergoing Allo-Hematopoietic Stem Cell Transplant	39.1; 34.8	—
SECONDARY Number of Participants to Complete Conversion to >95% Donor Chimerism	23; 23	—
SECONDARY Cluster of Differentiation 4 (CD4) Reconstitution	284	—
SECONDARY Best Response Post-Hematopoietic Stem Cell Transplant EOCH (Etoposide, Vincristine, Cyclophosphamide, and Doxorubicin)	2; 4; 4; 2	—
SECONDARY Median Survival From Date of Progression	3.3; 19.1	.0003 sig

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.

Eligibility Criteria

INCLUSION CRITERIA: PATIENT

The following diagnoses will be considered:

Patients with Ewing's sarcoma family of tumors, or alveolar

rhabdomyosarcoma in one of the following categories:

Patients who present at the time of initial diagnosis with bone or bone marrow metastases may be enrolled after completion of standard front-line therapy. Standard front line therapy for alveolar rhabdomyosarcoma should include vincristine and cyclophosphamide, plus actinomycin D and/or adriamycin. For patients with Ewing's sarcoma, standard front line therapy should include vincristine, cyclophosphamide, adriamycin, ifosfamide and etoposide.
Patients with recurrence of tumor at any site less than one year after completing standard front-line therapy or with a second or subsequent recurrence at any time after completing standard front-line therapy.
Patients with progression or persistence of disease while receiving standard front-line chemotherapy who cannot achieve a complete response (CR) with local treatment modalities.
The following patients with desmoplastic small round cell tumor are eligible after receiving front line standard therapy, which is defined as a regimen containing at least vincristine, cyclophosphamide, and adriamycin:
unresectable disease
metastatic tumor (abdominal and extra-abdominal disease)
progressive or persistent while receiving standard therapy
recurrence within one year of completing therapy
Patients without evaluable tumor at the time of enrollment are eligible
Patients who have previously received high-dose chemotherapy with autologous stem cell rescue are eligible for this trial.
Patient age 5-35 at enrollment.
Availability of a 5 or 6 antigen human leukocyte antigen (HLA)-matched first-degree relative donor (single HLA-A or B mismatch allowed). Genotypically identical twins may serve as stem cell donors. Genotypic identity must be confirmed by restrictive fragment length polymorphism (RFLP) analysis.
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 or, for children less than or equal 10 years of age, Lansky greater than or equal 60
Cardiac function: Left ventricular ejection fraction greater than or equal to 45% by multi-gated acquisition scan (MUGA), fractional shortening greater than or equal 28% by echocardiogram (ECHO) or left ventricular ejection fraction greater than or equal 55% by ECHO.
Pulmonary function: carbon monoxide diffusing capacity (DLCO) greater than or equal to 50% of the expected value corrected for alveolar volume.
Renal function: Age-adjusted normal serum creatinine according to the following table or a creatinine clearance greater than or equal to 60 ml/min/1.73 m^2. Age (years) Maximum serum creatinine (mg/dl) less than or equal to 5 0.8 greater than 5, less than or equal to 10 1.0 greater than 10, less than or equal to15 1.2, greater than 15 1.5
Liver function: Serum total bilirubin less than 2 mg/dl, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 times upper limit of normal.
Marrow function: absolute neutrophil count (ANC) must be greater than 750/mm^3 (unless due to underlying disease in which case there is no grade restriction), platelet count must be greater than or equal to 75,000/mm^3 (not achieved by transfusion) unless due to underlying disease in which case there is no grade restriction). Lymphopenia, cluster of differentiation 4 (CD4) lymphopenia, leukopenia, and anemia will not render patients ineligible.
Ability to give informed consent. For patients less than18 years of age their legal guardian must give informed consent. Pediatric patients will be included in age appropriate discussion in order to obtain verbal assent.
Durable power of attorney form completed (patients greater than or equal to18 years of age only).

INCLUSION CRITERIA: DONOR

Weight greater than or equal 15 kilograms.
First degree relative with genotypic identity at 5 or 6 HLA

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00043979). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.