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

NCT ID: NCT00007813

Last Updated: 2020-02-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1997-05-31
• Study Completion Date: 2005-02-01

Brief Summary

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.

Detailed Description

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.

Conditions

Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Liver Cancer; Neuroblastoma; Ovarian Cancer; Sarcoma; Testicular Germ Cell Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

Group Type: EXPERIMENTAL

filgrastim

Intervention Type: BIOLOGICAL

carboplatin

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

autologous bone marrow transplantation

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Interventions

filgrastim

Intervention Type: BIOLOGICAL

carboplatin

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

autologous bone marrow transplantation

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

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

• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Amgen

INDUSTRY

Sponsor Role: collaborator

Baxter Healthcare Corporation

INDUSTRY

Sponsor Role: collaborator

Nexell Therapeutics Inc

UNKNOWN

Sponsor Role: collaborator

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Allen R. Chen, MD, PhD, MHS

Role: STUDY_CHAIR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Johns Hopkins Oncology Center

Baltimore, Maryland, United States

Countries

United States

References

Leung W, Chen AR, Klann RC, et al.: Tumor cells frequently detected in marrow and mobilized blood hematopoietic grafts in neuroblastoma and primitive neuroblastoma and primitive neuroectodermal tumor: purging by immunomagnetic CD34+ cell selection. [Abstract] Blood 88: A-1917, 482a, 1996.

Reference Type: BACKGROUND

Chen AR, Cohen KJ, Eby LL, et al.: Heterogenous mobilization of CD34+ blood stem cells for autologous rescue of children with poor prognosis solid tumors. [Abstract] Blood 86: 403a, 1995.

Reference Type: BACKGROUND

Chen AR, Wiangon S, Noga SJ, et al.: Rapid engraftment of CD34+ selected peripheral blood stem cells (PBSC) after high-dose chemotherapy for patients with recurrent, refractory, or metastatic pediatric solid tumors. [Abstract] Proceedings of the American Society of Clinical Oncology 17: A2038, 530a, 1998.

Reference Type: RESULT

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. doi: 10.1038/sj.bmt.1701471.

Reference Type: RESULT

PMID: 9849694 (View on PubMed)

Other Identifiers

CDR0000064263

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-V95-0688

Identifier Type: REGISTRY

Identifier Source: secondary_id

94-12-23-02

Identifier Type: OTHER

Identifier Source: secondary_id

JHOC-9512

Identifier Type: -

Identifier Source: org_study_id