Treatment of Newly Diagnosed Brain Tumors With Chemotherapy and Radiation Using Cells Modified for Chemoprotection and an Experimental Drug to Decrease the Tumor Cell Resistance to Chemotherapy

NCT00272870 | Terminated Phase 1 DMC

• 1 other identifier: CCHMCEH003
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Cure rates for patients with high grade glioma remain disappointing, in part because tumor cells are often resistant to chemotherapy, and because using higher doses of chemotherapy causes damage to normal blood cells. This trial is designed to try to overcome both of these barriers. The idea is to make tumor cells more sensitive to a chemotherapy agent, Temozolomide, by using 06Benzylguanine (06BG). In addition, patients will have a portion of their blood cells modified by the insertion of a chemotherapy resistance gene which may help protect blood cells from damage by the combination of the Temozolomide and 06BG.

Conditions

Glioblastoma Multiforme (WHO Grade IV); Anaplastic Astrocytoma (WHO Grade III)

Outcome Measures

Primary Outcomes (1)

• To assess the safety and feasibility of infusing autologous PBSC transduced with MSCV-MGMTP140K construct, using the fibronectin component CH-296 to assist gene transfer.

  5 years

Secondary Outcomes (2)

• Assess the efficiency of gene transfer and durability of transgene expression in this clinical setting.

  5 years

• Assess the degree of chemotherapy resistance in transduced cells, and the ability to enrich the population of transduced stem cells with subsequent courses of chemotherapy.

  5 years

Interventions

06Benzylguanine DRUG

120 mg/m2/day; given Day 1-5 for up to 6 courses in Block 3

MGMT P140K GENETIC

Gene manipulated cells, patients are not expected to receive greater than approximately 10 x 10e6 transduced CD34+ cells/kg

Meltenyi CliniMacs DEVICE

Device used for CD34+ cell separation of peripheral collection

Eligibility Criteria

• Age: 5 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age \> 5 years and \< 55 years. NOTE: Subjects ages 5-30 are eligible to be treated at Cincinnati Children's Hospital Medical Center; subjects over age 30 will be treated at Ohio State University Comprehensive Cancer Center.
• Anticipated life expectancy of at least nine months 3.1.3 Karnofsky score \> 50 for patients \> 10 years of age, and Lansky score \> 50 for patients \< 10 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Patients must have one of the following newly-diagnosed central nervous system tumors, confirmed by histologic verification: Glioblastoma multiforme (WHO grade IV) OR Anaplastic astrocytoma (WHO grade III)
• Patients older than 30 years that have undergone a gross total resection and who do not have measurable disease on post operative MRI; measurable disease as assessed by post operative MRI is required on patients 30 years of age or younger.
• Neurologic deficits and corticosteroid doses must be stable or decreasing at the time of study entry.
• Adequate organ function as defined by: Serum creatinine \< upper limit of normal, or GFR \> 70 ml/min/1.73 m2 Total bilirubin \< 2.0 mg/dl; SGPT (ALT) AND SGOT (AST) \< 2.5x upper limit of normal; serum albumin \> 2.0 g/dL Absolute neutrophil count \> 1,000/µl, platelet count \> 75,000/µl independent of transfusions
• The patient and/or the patient's legally authorized guardian must give written informed consent according to local Institutional and/or University Human Experimentation Committee requirements.
• Women or men with reproductive potential must use effective contraception throughout the study. Effective contraception methods for women would include either an oral or transdermal contraceptive, injectable contraceptive (e.g., Depo-Provera), or contraceptive implants (e.g., intrauterine device). All males on study must agree to the use of condoms during intercourse.
• Women of reproductive potential must have a negative serum pregnancy test.

You may not qualify if:

• Any prior treatment with chemotherapy or radiotherapy.
• Any tumor arising in the spine or brainstem.
• Presence of metastatic disease in the spine.
• WHO grade III oligodendroglioma or oligoastrocytoma.
• Active infection at time of study entry.
• Pregnant or lactating females are excluded, because of the known teratogenic effects of alkylating agents.
• Known HIV-positive patients. Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy and are excluded from this study. An infectious disease screen consisting of HIV I \& II Ab and NAT, HTLV I \& II Ab, RPR, Hepatitis B Surface Ag, Hepatitis B Core Ab and Hepatitis C Ab will be obtained at study entry.
• Concurrent treatment with other investigational anti-cancer agents.
• Serious illness or medical condition which would not permit the patient to be managed according to the protocol.
• Low-grade glioma (WHO Grade 1-2).

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Glioblastoma; Astrocytoma; Lymphoma, Follicular

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Punam Malik, MD

  Cincinnati Childrens Hospital Medical Center

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2006
• First Posted: January 9, 2006
• Study Start: December 1, 2005
• Primary Completion: December 1, 2008
• Study Completion: August 1, 2012
• Last Updated: August 29, 2012

Record last verified: 2012-08

Locations

US (1)