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TREATMENT OF CHILDREN AND YOUNG ADULTS WITH RECURRENT/REFRACTORY SOLID TUMORS WITH HIGH DOSE ETOPOSIDE AND CARBOPLATIN PLUS ESCALATING DOSE CYCLOPHOSPHAMIDE, FOLLOWED BY HEMATOPOIETIC RESCUE USING AUTOLOGOUS CD34+ SELECTED BLOOD STEM CELLS: A PILOT STUDY


Phase 1
N/A
35 Years
Open (Enrolling)
Both
Brain and Central Nervous System Tumors, Childhood Germ Cell Tumor, Extragonadal Germ Cell Tumor, Liver Cancer, Neuroblastoma, Ovarian Cancer, Sarcoma, Testicular Germ Cell Tumor

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Trial Information

TREATMENT OF CHILDREN AND YOUNG ADULTS WITH RECURRENT/REFRACTORY SOLID TUMORS WITH HIGH DOSE ETOPOSIDE AND CARBOPLATIN PLUS ESCALATING DOSE CYCLOPHOSPHAMIDE, FOLLOWED BY HEMATOPOIETIC RESCUE USING AUTOLOGOUS CD34+ SELECTED BLOOD STEM CELLS: A PILOT STUDY


OBJECTIVES:

- Determine whether autologous transplantation of mobilized CD34+ peripheral blood stem
cells (PBSC) can provide complete hematologic reconstitution after myeloablative
chemotherapy comprising etoposide (VP-16) and carboplatin (CBDCA) in patients with
metastatic or recurrent rhabdomyosarcoma, neuroblastoma, Ewing's sarcoma/primitive
neuroectodermal tumor, germ cell tumors, childhood brain tumors, or hepatoblastoma.

- Determine the frequency and yield of CD34+ PBSC and granulocyte-macrophage
colony-forming units (GM-CFU) that are mobilized, harvested, and purified after a
single priming course of high-dose cyclophosphamide (CTX) followed by filgrastim
(G-CSF).

- Correlate the number of CD34+ cells and GM-CFU in the autologous PBSC graft with time
to engraftment of white blood cells, neutrophils, and platelets in these patients.

- Determine the optimal day of PBSC harvest after a single priming course of high-dose
CTX and G-CSF in these patients.

- Determine whether CD34+ PBSC rescue and daily post-transplantation G-CSF decrease the
time to hematopoietic recovery after high-dose VP-16 and CBDCA compared to historical
results achieved in similar patients rescued with bone marrow.

- Compare the tumor cell content of marrow, mobilized blood, and purified CD34+ PBSC
graft preparations.

- Determine the optimal timing of PBSC mobilization and harvest in relation to extent of
prior chemotherapy in these patients.

- Determine the feasibility of a single leukapheresis for PBSC harvest in children.

- Determine the toxic effects of this regimen in these patients.

- Determine the antitumor activity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of cyclophosphamide.

Mobilization/harvest: Patients receive cyclophosphamide IV over 90 minutes on day 0 and
filgrastim (G-CSF) subcutaneously or IV over 30 minutes on days 2-15 or until blood counts
recover. Peripheral blood stem cells (PBSC) are harvested and selected for CD34+ cells on
day 15. Bone marrow is also harvested in case insufficient PBSC are harvested.

Preparative regimen/transplantation: Patients receive carboplatin IV over 1 hour and
etoposide IV continuously on days -6 to -4. Cyclophosphamide is administered IV over 1 hour
on days -3 and -2 or IV continuously on days -3 and -2, -4 to -2, -5 to -2, or -6 to -2.
PBSC or bone marrow is reinfused on day 0.

Cohorts of 3-10 patients receive escalating doses of cyclophosphamide until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the highest dose at which 20% of
patients experience dose-limiting toxicity.

At least 6 additional patients receive cyclophosphamide at the MTD.

PROJECTED ACCRUAL: A minimum of 36 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically proven malignant solid tumor, including any of the following:

- Rhabdomyosarcoma

- Neuroblastoma

- Ewing's sarcoma/primitive neuroectodermal tumor

- Germ cell tumors

- Childhood brain tumors

- Hepatoblastoma

- Metastatic disease OR has failed at least first-line therapy

- Ineligible for higher priority protocols

PATIENT CHARACTERISTICS:

Age:

- Under 36 at transplantation

Performance status:

- Karnofsky 60-100%

Life expectancy:

- At least 8 weeks

Hematopoietic:

- Absolute neutrophil count at least 1,000/mm3

- Platelet count at least 75,000/mm3

Hepatic:

- Bilirubin no greater than 1.5 mg/dL

- Liver function tests no greater than 2 times normal OR

- No active hepatitis on liver biopsy

- No hepatitis B infection

Renal:

- Creatinine no greater than 1.5 mg/dL OR

- Glomerular filtration rate (preferably measured) greater than 60% of normal

Cardiovascular:

- Left ventricular ejection fraction at least 45%

- No active congestive heart failure

- No active arrhythmia

Pulmonary:

- Age 8 and under: clinically normal pulmonary function

- Over age 8: FEV1 and FVC at least 50% predicted

- Arterial blood gases normal and DLCO at least 50% if spirograms difficult to

- interpret due to poor patient effort, recent surgery, or pulmonary tumor

- involvement

Other:

- No mucositis or mucosal infection prior to myeloablative chemotherapy

- HIV negative

- Not pregnant

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Allen R. Chen, MD, PhD, MHS

Investigator Role:

Study Chair

Investigator Affiliation:

Sidney Kimmel Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000064263

NCT ID:

NCT00007813

Start Date:

May 1995

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • Childhood Germ Cell Tumor
  • Extragonadal Germ Cell Tumor
  • Liver Cancer
  • Neuroblastoma
  • Ovarian Cancer
  • Sarcoma
  • Testicular Germ Cell Tumor
  • recurrent childhood rhabdomyosarcoma
  • childhood craniopharyngioma
  • recurrent childhood brain tumor
  • disseminated neuroblastoma
  • stage 4S neuroblastoma
  • recurrent neuroblastoma
  • stage IV childhood liver cancer
  • recurrent childhood liver cancer
  • childhood hepatoblastoma
  • childhood central nervous system germ cell tumor
  • stage III malignant testicular germ cell tumor
  • recurrent malignant testicular germ cell tumor
  • childhood germ cell tumor
  • stage IV ovarian germ cell tumor
  • recurrent ovarian germ cell tumor
  • extragonadal germ cell tumor
  • childhood oligodendroglioma
  • childhood choroid plexus tumor
  • childhood grade III meningioma
  • recurrent childhood cerebellar astrocytoma
  • recurrent childhood cerebral astrocytoma
  • recurrent childhood medulloblastoma
  • recurrent childhood visual pathway and hypothalamic glioma
  • previously treated childhood rhabdomyosarcoma
  • metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor
  • recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
  • recurrent childhood ependymoma
  • childhood teratoma
  • childhood malignant testicular germ cell tumor
  • childhood malignant ovarian germ cell tumor
  • childhood extragonadal germ cell tumor
  • recurrent childhood malignant germ cell tumor
  • childhood atypical teratoid/rhabdoid tumor
  • Liver Neoplasms
  • Nervous System Neoplasms
  • Neuroblastoma
  • Ovarian Neoplasms
  • Central Nervous System Neoplasms
  • Neoplasms, Germ Cell and Embryonal
  • Neuroectodermal Tumors, Primitive, Peripheral
  • Sarcoma

Name

Location

Johns Hopkins Oncology CenterBaltimore, Maryland  21287