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Pilot Study of Allogeneic/Syngeneic Blood Stem Cell Transplantation in Patients With High-Risk and Recurrent Pediatric Sarcomas

Phase 2
5 Years
35 Years
Not Enrolling

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Trial Information

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.

Inclusion Criteria


The following diagnoses will be considered:

1. 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 CR with local treatment modalities.

2. 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 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 RFLP

- 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 MUGA, fractional shortening greater than or equal 28% by ECHO or
left ventricular ejection fraction greater than or equal 55% by ECHO.

- Pulmonary function: 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 m2. 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 AST and ALT
less than or equal to 2.5 times upper limit of normal.

- Marrow function: ANC must be greater than 750/mm3 (unless due to underlying
disease in which case there is no grade restriction), platelet count must
be greater than or equal to 75,000/mm3 (not achieved by transfusion) unless
due to underlying disease in which case there is no grade restriction).
Lymphopenia, 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).


- Weight greater than or equal 15 kilograms.

- First degree relative with genotypic identity at 5 or 6 HLA loci (single HLAA or B
locus mismatch allowed). Genotypically identical twins may serve as stem cell donors.
Genotypic identity must be confirmed by RFLP analysis.

- For donors less than18 years of age, he/she must be the oldest suitable donor, their
legal guardian must give informed consent, the donor must give verbal assent, and
he/she must be cleared by social work and a mental health specialist to participate.

- For donors greater than or equal to 18 years of age, ability to give informed

- Adequate peripheral venous access for apheresis or consent to use a temporary central
venous catheter for apheresis.

- Donor selection criteria will be in accordance with NIH/CC Department of Transfusion
Medicine Standards.


- Uncontrolled fungal infection.

- History of untreated CNS tumor involvement. Extradural masses which have not invaded
the brain parenchyma (as is commonly observed in Ewing's sarcoma family of tumors) or
parameningeal tumors (as is commonly observed in rhabdomyosarcoma) without evidence
for leptomeningeal spread will not render the patient ineligible. Patients with
previous CNS tumor involvement that has been treated and has been stable for at least
6 weeks are eligible.

- Lactating or pregnant females.

- HIV positive (due to unacceptable risk following allogeneic transplantation).

- Hepatitis B surface antigen (HBsAg) positive or hepatitis C antibody positive with
elevated liver transaminases. All patients with chronic active hepatitis (including
those on treatment) are ineligible.

- High risk of inability to comply with transplant protocol, or inability to give
appropriate informed consent in the estimation of the PI, social work, or the stem
cell transplant team.

- Fanconi Anemia


- History of medical illness which poses a risk to donation in the estimation of the PI
or the Department of Transfusion Medicine physician including, but not limited to
stroke, hypertension that is not controlled with medication, or heart disease.
Individuals with symptomatic angina or a history of coronary bypass grafting or
angioplasty will not be eligible.

- History of congenital hematologic, immunologic, oncologic or metabolic disorder,
which poses a prohibitive risk to the recipient in the estimation of the PI.

- Anemia (Hb less than 11 gm/dl) or thrombocytopenia (platelets less than 100,000/micro

- Lactating or pregnant females. Donors of childbearing potential must use an effective
method of contraception during the time they are receiving G-CSF. The effects of
cytokine administration on a fetus are unknown and may be potentially harmful. The
effects upon breast milk are also unknown and may potentially be harmful to the

- HIV-positive, hepatitis B surface antigen (HBsAg) positive or hepatitis C antibody
positive. Donors are providing an allogeneic blood product and there is the potential
risk of transmitting these viral illnesses to the recipient.

- High risk of inability to comply with transplant protocol.

Type of Study:


Study Design:

Primary Purpose: Treatment

Outcome Measure:


Safety Issue:


Principal Investigator

Kristin Baird, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:




Start Date:

August 2002

Completion Date:

April 2012

Related Keywords:

  • Sarcoma
  • Ewing's Sarcoma
  • Rhabdomyosarcoma
  • Desmoplastic Small Round Cell Tumor
  • Sarcoma
  • Ewing Sarcoma
  • Sarcoma



National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland  20892