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Peripheral Stem Cell Transplantation Plus Chemotherapy in Treating Patients With Malignant Solid Tumors - Article


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Salivary Gland Cancer, Childhood


Clinical Trial: Peripheral Stem Cell Transplantation Plus Chemotherapy in Treating Patients With Malignant Solid Tumors

This study is no longer recruiting patients.

Sponsored by: Johns Hopkins Oncology Center
Information provided by: National Cancer Institute (NCI)

Purpose

RATIONALE: Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase I trial to evaluate the effectiveness of peripheral stem cell transplantation and chemotherapy in treating patients with malignant solid tumors.

Condition Treatment or Intervention Phase
childhood liver cancer
Bone Cancer
Testicular Cancer
Brain Tumor
 Drug: carboplatin
 Drug: cyclophosphamide
 Drug: etoposide
 Drug: filgrastim
Phase I

MedlinePlus related topics:  Bone Cancer;   Brain Cancer;   Liver Cancer;   Testicular Cancer

Study Type: Interventional
Study Design: Treatment

Official Title: Phase I Pilot Study of High-Dose Etoposide, Carboplatin, and Cyclophosphamide Followed By Autologous CD34+ Peripheral Blood Stem Cell Rescue in Patients With Metastatic or Recurrent Rhabdomyosarcoma, Neuroblastoma, Ewing's Sarcoma/Primitive Neuroectodermal Tumor, Germ Cell Tumors, Childhood Brain Tumors, or Hepatoblastoma

Further Study Details: 

Study start: May 2000

OBJECTIVES: I. 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. II. 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). III. 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. IV. Determine the optimal day of PBSC harvest after a single priming course of high-dose CTX and G-CSF in these patients. V. Determine whether CD34+ PBSC rescue and daily post-transplant 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. VI. Compare the tumor cell content of marrow, mobilized blood, and purified CD34+ PBSC graft preparations. VII. Determine the optimal timing of PBSC mobilization and harvest in relation to extent of prior chemotherapy in these patients. VIII. Determine the feasibility of a single leukapheresis for PBSC harvest in children. IX. Determine the toxic effects of this regimen in these patients. X. Determine the antitumor activity of this regimen in these patients.

PROTOCOL OUTLINE: This is a dose escalation study of cyclophoshamide. 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.

Eligibility

Ages Eligible for Study:  up to  35 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

  • Histologically proven malignant solid tumor that is metastatic or has failed at least first-line therapy, e.g.: Rhabdomyosarcoma; Neuroblastoma; Ewing's sarcoma/primitive neuroectodermal tumor; Germ cell tumors; Childhood brain tumors; Hepatoblastoma
  • Ineligible for higher priority protocols

--Prior/Concurrent Therapy--

  • See Disease Characteristics

--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 GFR (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

Location Information


Maryland
      Johns Hopkins Oncology Center, Baltimore,  Maryland,  21231-2410,  United States

Study chairs or principal investigators

Allen R. Chen,  Study Chair,  Johns Hopkins Oncology Center   

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Publications

Leung W, Chen AR, Klann RC, Moss TJ, Davis JM, Noga SJ, Cohen KJ, Friedman AD, Small D, Schwartz CL, Borowitz MJ, Wharam MD, Paidas CN, Long CA, Karandish S, McMannis JD, Kastan MB, Civin CI. Frequent detection of tumor cells in hematopoietic grafts in neuroblastoma and Ewing's sarcoma. Bone Marrow Transplant. 1998 Nov;22(10):971-9.

Study ID Numbers:  CDR0000064263; JHOC-9512; NCI-V95-0688
Record last reviewed:  March 2004
Last Updated:  October 13, 2004
Record first received:  January 6, 2001
ClinicalTrials.gov Identifier:  NCT00007813
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005


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October 6, 2008



Page Updated: September 23, 2004
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