BG & TMZ Therapy of Glioblastoma Multiforme

NCT01269424 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: CASE63078274U01CA062502
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. O6-benzylguanine may help temozolomide work better by making tumor cells more sensitive to the drug. Giving genetically modified peripheral blood stem cells during or after treatment may prevent side effects caused by chemotherapy. PURPOSE: This clinical trial studies O6-benzylguanine and temozolomide in combination with genetically modified peripheral blood stem cells in treating patients with newly diagnosed glioblastoma multiforme.

Conditions

Glioblastoma Multiforme

Keywords

adult giant cell glioblastoma; adult glioblastoma; adult gliosarcoma

Outcome Measures

Primary Outcomes (1)

• Feasibility and safety of infusing autologous P140K MGMT-transduced hematopoietic progenitors into patients with GBM

  Patients will be assessed for clinical symptoms and side-effects - CTCAE v 4.0 - from time of treatment until protocol is stopped due to toxicity, progression, patient choice, or patient election to enroll on new therapeutic option.

  up to 5 years

Secondary Outcomes (5)

• Successful transduction rate

  up to 4 years

• To evaluate the in vivo enrichment of P140K expressing hematopoietic cells by repeated treatments of BG and TMZ

  up to 4 years

• Progression-free

  up to 5 years

• Number of patients with radiological progression

  up to 5 years

• Overall Survival

  up to 5 years

Study Arms (3)

Cohort 1

ACTIVE COMPARATOR

LV gene transfer after concurrent chemo-radiotherapy

Biological: MGMTP140K-encoding retroviral vector; Drug: O6-benzylguanine; Drug: temozolomide; Other: laboratory biomarker analysis; Procedure: autologous hematopoietic stem cell transplantation; Procedure: in vitro-treated peripheral blood stem cell transplantation; Radiation: radiation therapy

Cohort 2

ACTIVE COMPARATOR

LV gene transfer prior to concurrent chemo-radiotherapy

Biological: MGMTP140K-encoding retroviral vector; Drug: O6-benzylguanine; Drug: temozolomide; Other: laboratory biomarker analysis; Procedure: autologous hematopoietic stem cell transplantation; Procedure: in vitro-treated peripheral blood stem cell transplantation; Radiation: radiation therapy

Cohort 3

ACTIVE COMPARATOR

Intra patient dose escalation of TMZ in patients with evidence of P140K marked cells

Biological: MGMTP140K-encoding retroviral vector; Drug: O6-benzylguanine; Drug: temozolomide; Other: laboratory biomarker analysis; Procedure: autologous hematopoietic stem cell transplantation; Procedure: in vitro-treated peripheral blood stem cell transplantation; Radiation: radiation therapy

Interventions

MGMTP140K-encoding retroviral vector BIOLOGICAL

Cohort 1; Cohort 2; Cohort 3

O6-benzylguanine DRUG

Cohort 1; Cohort 2; Cohort 3

temozolomide DRUG

Cohort 1; Cohort 2; Cohort 3

laboratory biomarker analysis OTHER

Cohort 1; Cohort 2; Cohort 3

autologous hematopoietic stem cell transplantation PROCEDURE

Cohort 1; Cohort 2; Cohort 3

in vitro-treated peripheral blood stem cell transplantation PROCEDURE

Cohort 1; Cohort 2; Cohort 3

radiation therapy RADIATION

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically confirmed, newly diagnosed, supratentorial GBM who have undergone gross total tumor resections or near gross total resection (resection of \>90% of enhancing tumor demonstrated by MRI) are eligible up to their third post-operative week. Patients with infratentorial disease, multifocal or leptomeningeal disease will be excluded. In general, patients will not have \> 1 cm residual measurable or evaluable disease after surgical tumor resection.
• ECOG performance status 0-2 or Karnofsky ≥ 70.
• Patients must have received no myelosuppressive chemotherapy prior to the diagnosis of GBM.
• Life expectancy of at least 12 weeks.
• Adequate hematologic (ANC ≥ 1,000/mm3, platelets ≥ 100,000/mm3, Hgb ≥ 9.5) , hepatic (Bilirubin ≤ 2.0 mg/dl, AST and ALT less than or equal to 3 times upper limit of normal, prothrombin time \<1.2 times normal), and renal (Serum creatinine ≤ 2.0 mg/dl or Creatinine Clearance ≥ 60mL/min/1.73 m2 for subjects with serum creatinine levels above institutional normal) . These tests will be repeated within 2 weeks of treatment with BG and TMZ, and must meet the same criteria.
• EKG without evidence of acute cardiac disease.
• Left ventricular ejection fraction (LVEF) ≥ 40
• Post-operative steroids are tapered to ≤ 24 mg decadron/d
• Patients of child-bearing potential must be using single barrier contraception
• Willingness and ability to provide informed consent.
• Patient must have all sutures removed prior to registration
• Patient must be considered to be clinically stable.

You may not qualify if:

• Medical condition associated with immunosuppression, active infection or medical illness which may jeopardize patient safety.
• Pregnant or lactating women. There is data to indicate that TMZ is teratogenic and carcinogenic. Thus, its use in pregnant women would confer unnecessary risk to the fetus.
• Patients with symptomatic pulmonary disease and other severe co-morbid conditions
• Patients with cardiac insufficiency and an LVEF of \< 40%. History of acute coronary event disease or arrhythmia within 6 months prior to enrollment
• Prior chemotherapy (including gliadel wafers) or hematopoietic cell transplantation.
• Inability to undergo repeated MRI evaluation.
• Prior diagnosis of malignant disease within a three year period with the exception of surgically cured basal cell carcinoma or carcinoma in situ of the cervix
• Mental incapacity or psychiatric illness preventing informed consent

Sponsors & Collaborators

• Stanton Gerson MD: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5047, United States

Location

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

O(6)-benzylguanine; Temozolomide; Radiotherapy

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Study Officials

• Andrew Sloan, MD

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Case Comprehensive Cancer Center

Study Record Dates

• First Submitted: December 31, 2010
• First Posted: January 4, 2011
• Study Start: November 22, 2011
• Primary Completion: December 7, 2020
• Study Completion: September 26, 2022
• Last Updated: March 2, 2023

Record last verified: 2023-03

Locations

US (1)