Peripheral Stem Cell Transplantation Plus Chemotherapy in Treating Patients With Malignant Solid Tumors
| Status: | Completed |
|---|---|
| Conditions: | Ovarian Cancer, Liver Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Brain Cancer, Brain Cancer, Brain Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any - 35 |
| Updated: | 3/17/2019 |
| Start Date: | May 31, 1997 |
| End Date: | February 1, 2005 |
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
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: This phase I trial is studying the side effects and best dose of cyclophosphamide
when given together with combination chemotherapy and a peripheral stem cell transplant in
treating patients with malignant solid tumors.
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: This phase I trial is studying the side effects and best dose of cyclophosphamide
when given together with combination chemotherapy and a peripheral stem cell transplant in
treating patients with malignant solid tumors.
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.
- 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.
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
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