Combination Chemotherapy Plus Gene Therapy in Treating Patients With CNS Tumors

NCT ID: NCT00005796

Last Updated: 2015-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-02-29
• Study Completion Date: 2011-12-31

Brief Summary

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.

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.

Conditions

Bone Marrow Suppression; Brain and Central Nervous System Tumors; Drug/Agent Toxicity by Tissue/Organ

Study Design

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

Study Groups

Single arm

PCV therapy

Group Type: EXPERIMENTAL

filgrastim

Intervention Type: PROCEDURE

GCSF is given after chemo administration

gene therapy

Intervention Type: BIOLOGICAL

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

lomustine

Intervention Type: DRUG

chemotherapy is administered every 21 days

procarbazine hydrochloride

Intervention Type: DRUG

chemotherapy is administered every 21 days.

vincristine sulfate

Intervention Type: DRUG

chemotherapy is administered every 21 days

in vitro-treated peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

stem cells are reinfused after chemotherapy administration

Interventions

filgrastim

GCSF is given after chemo administration

Intervention Type: PROCEDURE

gene therapy

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

Intervention Type: BIOLOGICAL

lomustine

chemotherapy is administered every 21 days

Intervention Type: DRUG

procarbazine hydrochloride

chemotherapy is administered every 21 days.

Intervention Type: DRUG

vincristine sulfate

chemotherapy is administered every 21 days

Intervention Type: DRUG

in vitro-treated peripheral blood stem cell transplantation

stem cells are reinfused after chemotherapy administration

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Indiana University Melvin and Bren Simon Cancer Center

OTHER

Sponsor Role: collaborator

Indiana University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

James Croop, MD, PhD

Role: STUDY_CHAIR

Riley's Children Cancer Center at Riley Hospital for Children

Locations

Indiana University Cancer Center

Indianapolis, Indiana, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

IUMC-9607-22

Identifier Type: -

Identifier Source: secondary_id

NCI-H00-0049

Identifier Type: -

Identifier Source: secondary_id

9607-22

Identifier Type: -

Identifier Source: org_study_id