Combination Chemotherapy Plus Gene Therapy in Treating Patients With CNS Tumors
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|ClinicalTrials.gov Identifier: NCT00005796|
Recruitment Status : Completed
First Posted : April 28, 2004
Last Update Posted : March 25, 2015
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Inserting a specific gene into a person's peripheral stem cells may improve the body's ability to fight cancer or make the cancer more sensitive to chemotherapy.
PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus gene therapy in treating patients who have CNS tumors.
|Condition or disease||Intervention/treatment||Phase|
|Bone Marrow Suppression Brain and Central Nervous System Tumors Drug/Agent Toxicity by Tissue/Organ||Procedure: filgrastim Biological: gene therapy Drug: lomustine Drug: procarbazine hydrochloride Drug: vincristine sulfate Procedure: in vitro-treated peripheral blood stem cell transplantation||Phase 1|
OBJECTIVES: I. Determine the toxicity (detection of replication competent retrovirus) associated with CD34+ cells transduced with a retroviral vector expressing human O6-methylguanine DNA methyltransferase in adult and pediatric patients with poor prognosis CNS tumors. II. Determine the safety of genetic modification of cells carried out in the presence (ex vivo) of recombinant fibronectin (FN) fragment utilized to assist in retroviral entry into mammalian cells. III. Determine any evidence of engraftment of cells exposed to FN during retroviral transduction. IV. Determine any evidence of antibodies to FN following infusion of cells exposed to FN during ex vivo retroviral transduction.
OUTLINE: Patients with surgically approachable lesions undergo maximal surgical debulking that allows preservation of good neurologic functioning. Harvest: Patients receive filgrastim (G-CSF) subcutaneously or IV beginning 4 days prior to initiation of first leukapheresis and continuing until completion of harvest. Peripheral blood stem cells are harvested and selected for CD34+ cells which are transduced with a fibronectin assisted retroviral vector expressing human O6-methylguanine DNA methyltransferase. Intensification: Patients receive oral lomustine and vincristine IV on day 0 and oral procarbazine on days 1-7. Treatment repeats every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with newly diagnosed tumors may undergo involved field radiotherapy (IF-RT) after completion of the third course of chemotherapy and may begin the fourth course of chemotherapy after completion of IF-RT. Transplantation: Two-thirds of the transduced CD34+ cells are reinfused on day 9 of the first course of chemotherapy. The remaining portion (one-third) of the transduced CD34+ cells are reinfused on day 9 of the second course of chemotherapy. Untransduced CD34+ cells are reinfused on day 9 of the last 3 courses of chemotherapy. Patients are followed every 3 months for 6 months, every 4 months for 1 year, every 6 months through year 5, and then annually thereafter.
PROJECTED ACCRUAL: Approximately 15-20 patients will be accrued for this study within 1 year.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of Dose-Intensified Procarbazine, CCNU, Vincristine (PCV) for Poor Prognosis Pediatric and Adult Brain Tumors Utilizing Fibronectin-Assisted, Retroviral-Mediated Modification of CD34+ Peripheral Blood Cells With O6-Methylguanine DNA Methyltransferase|
|Study Start Date :||February 2000|
|Actual Primary Completion Date :||June 2003|
|Actual Study Completion Date :||December 2011|
Experimental: Single arm
GCSF is given after chemo administrationBiological: gene therapy
stem cells are collected and given back to the patients after chemotherapy adminstrationDrug: lomustine
chemotherapy is administered every 21 daysDrug: procarbazine hydrochloride
chemotherapy is administered every 21 days.Drug: vincristine sulfate
chemotherapy is administered every 21 daysProcedure: in vitro-treated peripheral blood stem cell transplantation
stem cells are reinfused after chemotherapy administration
- Determine the toxicity (detection of replication competent retrovirus) associated with CD34+ cells transduced with a retroviral vector expressing human O6-methylguanine DNA methyltransferase in adult and pediatric patients with poor prognosis CNS tumors. [ Time Frame: Year 2 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00005796
|United States, Indiana|
|Indiana University Cancer Center|
|Indianapolis, Indiana, United States, 46202-5265|
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|Study Chair:||James Croop, MD, PhD||Riley's Children Cancer Center at Riley Hospital for Children|