Combination Chemotherapy Plus Gene Therapy in Treating Patients With CNS Tumors

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2009 by Indiana University.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Indiana University Melvin and Bren Simon Cancer Center
Information provided by:
Indiana University
ClinicalTrials.gov Identifier:
NCT00005796
First received: June 2, 2000
Last updated: October 22, 2009
Last verified: October 2009
  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:


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
Estimated Study Completion Date: June 2012
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    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
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

Additional Information:
No publications provided

Responsible Party: Jim Croop, MD, 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: October 22, 2009
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:
Central Nervous System Neoplasms
Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Procarbazine
Vincristine
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 23, 2014