Combination Chemotherapy Plus Gene Therapy in Treating Patients With CNS Tumors - Full Text View

Purpose

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	Intervention	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


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Genes and Gene Therapy

Drug Information available for: Procarbazine hydrochloride Procarbazine Vincristine sulfate Lomustine

Genetic and Rare Diseases Information Center resources: Glioblastoma Oligodendroglioma Glioma Anaplastic Astrocytoma Medulloblastoma Anaplastic Oligodendroglioma Gliosarcoma Ependymoma Medulloblastoma, Childhood Childhood Brain Stem Glioma Brain Tumor, Adult Cerebellar Astrocytoma, Childhood Cerebral Astrocytoma, Childhood

U.S. FDA Resources

Further study details as provided by Indiana University:

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]


Enrollment:	10
Study Start Date:	February 2000
Study Completion Date:	December 2011
Primary Completion Date:	June 2003 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Single arm PCV therapy	Procedure: filgrastim GCSF is given after chemo administration Biological: gene therapy stem cells are collected and given back to the patients after chemotherapy adminstration Drug: lomustine chemotherapy is administered every 21 days Drug: procarbazine hydrochloride chemotherapy is administered every 21 days. Drug: vincristine sulfate chemotherapy is administered every 21 days Procedure: in vitro-treated peripheral blood stem cell transplantation stem cells are reinfused after chemotherapy administration

Arms

Assigned Interventions

Experimental: Single arm

PCV therapy

Procedure: filgrastim

GCSF is given after chemo administration

Biological: gene therapy

stem cells are collected and given back to the patients after chemotherapy adminstration

Drug: lomustine

chemotherapy is administered every 21 days

Drug: procarbazine hydrochloride

chemotherapy is administered every 21 days.

Drug: vincristine sulfate

chemotherapy is administered every 21 days

Procedure: in vitro-treated peripheral blood stem cell transplantation

stem cells are reinfused after chemotherapy administration

Detailed Description:

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.

Eligibility


Ages Eligible for Study:	5 Years and older (Child, Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS: Histologically proven newly diagnosed CNS tumors Eligible tumor types: Glioblastoma multiforme (WHO grade IV) Anaplastic astrocytoma (WHO grade III) Anaplastic oligodendroglioma (WHO grade III) Mixed anaplastic oligoastrocytoma (WHO grade III) Incompletely resected ependymoma Diffusely intrinsic pontine or medullary glioma Histology requirement waived OR Histologically proven recurrent or progressive CNS tumors Eligible tumor types: Same as above plus oligodendroglioma (WHO grade II) No brainstem tumors arising from the cervicomedullary region or midbrain without histologic proof of malignancy No supratentorial low grade astrocytomas (WHO grade I or II)

PATIENT CHARACTERISTICS: Age: 5 and over Performance status: ECOG 0-2 Life expectancy: At least 2 months Hematopoietic: Absolute neutrophil count greater than 1,000/mm3 Platelet count greater than 100,000/mm3 (transfusion independent) Hemoglobin greater than 10 g/dL at time of pulmonary function testing Hepatic: Bilirubin less than 1.2 mg/dL SGOT or SGPT less than 3 times normal Renal: Creatinine less than 1.5 mg/dL OR Creatinine clearance or radioisotope GFR greater than 70 mL/min Pulmonary: FEV1, FVC, and/or DLCO greater than 60% predicted Children who are uncooperative with pulmonary function tests must have the following: No evidence of dyspnea at rest No exercise intolerance Oxygen saturation (by pulse oximetry) greater than 94% on room air Other: Minimum weight of 10 kg Not pregnant or nursing No active infection

PRIOR CONCURRENT THERAPY: Biologic therapy: No growth factors after completion of study chemotherapy Chemotherapy: No prior nitrosourea or procarbazine Endocrine therapy: No concurrent dexamethasone as antiemetic Radiotherapy: No prior craniospinal radiotherapy Surgery: Not specified

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005796

Locations


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

Sponsors and Collaborators

Indiana University

Indiana University Melvin and Bren Simon Cancer Center

Investigators


Study Chair:	James Croop, MD, PhD	Riley's Children Cancer Center at Riley Hospital for Children

More Information


Responsible Party:	Indiana University
ClinicalTrials.gov Identifier:	NCT00005796 History of Changes
Other Study ID Numbers:	9607-22 IUMC-9607-22 NCI-H00-0049
Study First Received:	June 2, 2000
Last Updated:	March 23, 2015
Health Authority:	United States: Federal Government

Keywords provided by Indiana University:


recurrent adult brain tumor adult brain stem glioma adult ependymoma adult medulloblastoma adult glioblastoma childhood high-grade cerebral astrocytoma childhood oligodendroglioma adult anaplastic astrocytoma adult anaplastic oligodendroglioma adult mixed glioma drug/agent toxicity by tissue/organ	bone marrow suppression untreated childhood brain stem glioma recurrent childhood brain stem glioma untreated childhood cerebellar astrocytoma recurrent childhood cerebellar astrocytoma recurrent childhood cerebral astrocytoma recurrent childhood medulloblastoma newly diagnosed childhood ependymoma recurrent childhood ependymoma adult giant cell glioblastoma adult gliosarcoma

Additional relevant MeSH terms:


Nervous System Neoplasms Central Nervous System Neoplasms Neoplasms by Site Neoplasms Nervous System Diseases Vincristine Procarbazine Lomustine	Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Alkylating Alkylating Agents

ClinicalTrials.gov processed this record on September 26, 2016