Pilot Study of Allogeneic/Syngeneic Blood Stem Cell Transplantation in Patients With High-Risk and Recurrent Pediatric Sarcomas
- Treatment of pediatric sarcomas has enjoyed progress in the past 25 years for patients
with localized, chemosensitive disease and prognostic factors are now available to
identify subsets of patients who have very dismal prognoses; patients with primary
metastatic disease, especially those with bone and bone marrow metastases.
- Patients with primary chemoresistant disease and early recurrence also have very poor
prognoses and lack suitable treatment options. For these patients, it is critical that
alternative approaches to cytotoxic chemotherapy be identified.
- Basic laboratory studies have shown that Ewing's sarcoma is susceptible to immune
mediated mechanisms of cytolysis in vitro. Interestingly, for Ewing's sarcoma this
appears to be true for both chemosensitive and chemoresistant cell lines.
- Recent progress in the field of bone marrow transplantation has identified approaches
that can reproducibly induce allogeneic peripheral blood stem cell engraftment in
adults with hematologic malignancies. In some cases, this same approach has shown
beneficial effects for patients with solid tumors as a result of the development of
allogeneic, immune-mediated graft versus tumor effects.
- To determine if the transplantation of HLA matched, peripheral blood stem cells can
result in full donor engraftment (greater than 95 percent by day 100) in patients with
high risk-pediatric sarcomas.
- To identify and characterize the toxicities of HLA-matched PBSCT in patients with
high-risk pediatric sarcomas. In particular we will identify the incidence of GVHD and
the pace of immune reconstitution in this population.
- To determine if allogeneic graft-versus-tumor responses following allogeneic PBSCT can
induce clinically significant anti-tumor effects as measured by radiographic evidence
of antitumor responses following PBSCT in patients with measurable disease and improved
clinical outcome compared to historical controls in this patient population with a
universally poor outcome.
- Patients, age of greater than 4 years at enrolment to less than 30 years at diagnosis
and age less than 35 at enrolment, with ultra-high risk Ewing's sarcoma family of
tumors, desmoplastic small round cell tumor or alveolar rhabdomyosarcoma.
- Patients must have completed standard front-line therapy and salvage therapy.
- Patient must have the availability of a 5 or 6 antigen HLA-matched first-degree
relative donor or a genotypically identical twin.
- Patients must have adequate cardiac, pulmonary, renal, liver, and marrow function.
-Donor will be prepared for peripheral blood stem cell harvest with Filgrastim mobilization,
10 microg/kg per day SQ for 5-7 days until they have stem cell collected by apheresis. The
stem cells will then be cyropreserved.
Patients will receive 1 to 3 21 d cycles of Fludarabine-EPOCH induction chemotherapy. The
preparative regimen will consist of cyclophosphamide, fludarabine and meplphalan followed by
stem cell infusion. GVHD prophylaxis will consist of sirolimus and tacrolimus.
Primary Purpose: Treatment
Kristin Baird, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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