O6-Benzylguanine-Mediated Tumor Sensitization With Chemoprotected Autologous Stem Cell in Treating Patients With Malignant Gliomas

NCT00669669 | Terminated Phase 1 Results DMC

• 4 other identifiers: 2000.00NCI-2013-007018357RG1709046
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and best dose of temozolomide when given together with radiation therapy, carmustine, O6-benzylguanine, and patients' own stem cell (autologous) transplant in treating patients with newly diagnosed glioblastoma multiforme or gliosarcoma. Giving chemotherapy, such as temozolomide, carmustine, and O6-benzylguanine, and radiation therapy before a peripheral stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as filgrastim or plerixafor, and certain chemotherapy drugs, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy or radiation therapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy.

Conditions

Glioblastoma; Gliosarcoma

Outcome Measures

Primary Outcomes (2)

• Number of Participants Dose-limiting Toxicity (DLT)

  Defined as any grade 4 nonhematopoietic toxicity that is likely related to the investigational procedures (Part I)

  Up to 6 weeks after infusion

• Number of Participants With Retrovirus or Leukemia

  Replication competent retrovirus or diagnosis of leukemia

  Up to 2 years after infusion

Secondary Outcomes (8)

• Response Rate

  Up to 66 months

• Duration of Response

  Up to 65 months

• Time to Progression

  Up to 66 months.

• Number of Participants That Survived

  Up to 74 months

• Number of Participants With Chemoprotection

  Up to 66 months

Study Arms (1)

Treatment (chemotherapy, autologous stem cell transplant)

EXPERIMENTAL

See Detailed Description

Radiation: 3-Dimensional Conformal Radiation Therapy; Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Carmustine; Biological: Filgrastim; Procedure: In Vitro-Treated Peripheral Blood Stem Cell Transplantation; Radiation: Intensity-Modulated Radiation Therapy; Other: Laboratory Biomarker Analysis; Drug: O6-Benzylguanine; Drug: Plerixafor; Radiation: Proton Beam Radiation Therapy; Drug: Temozolomide

Interventions

3-Dimensional Conformal Radiation Therapy RADIATION

Undergo 3D conformal IMRT

Also known as: 3-dimensional radiation therapy, 3D CONFORMAL RADIATION THERAPY, 3D CRT, 3D-CRT, Conformal Therapy, Radiation Conformal Therapy

Treatment (chemotherapy, autologous stem cell transplant)

Autologous Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo autologous in vitro-treated peripheral blood stem cell transplant

Also known as: Autologous Stem Cell Transplantation

Treatment (chemotherapy, autologous stem cell transplant)

Carmustine DRUG

Given IV

Also known as: BCNU, Becenum, Becenun, BiCNU, Bis(chloroethyl) Nitrosourea, Bis-Chloronitrosourea, Carmubris, Carmustin, Carmustinum, FDA 0345, Gliadel, N,N'-Bis(2-chloroethyl)-N-nitrosourea, Nitrourean, Nitrumon, SK 27702, SRI 1720, WR-139021

Treatment (chemotherapy, autologous stem cell transplant)

Filgrastim BIOLOGICAL

Given SC

Also known as: Filgrastim XM02, G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tbo-filgrastim, Tevagrastim

Treatment (chemotherapy, autologous stem cell transplant)

In Vitro-Treated Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo autologous in vitro-treated peripheral blood stem cell transplant

Also known as: in vitro-treated PBPC transplantation, in vitro-treated peripheral blood progenitor cell transplantation

Treatment (chemotherapy, autologous stem cell transplant)

Intensity-Modulated Radiation Therapy RADIATION

Undergo 3D conformal IMRT

Also known as: IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy

Treatment (chemotherapy, autologous stem cell transplant)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (chemotherapy, autologous stem cell transplant)

O6-Benzylguanine DRUG

Given IV

Also known as: 6-O-BENZYLGUANINE, O(6)-Benzylguanine

Treatment (chemotherapy, autologous stem cell transplant)

Plerixafor DRUG

Given SC

Also known as: AMD 3100, JM-3100, Mozobil, SDZ SID 791

Treatment (chemotherapy, autologous stem cell transplant)

Proton Beam Radiation Therapy RADIATION

Undergo proton beam radiation therapy

Treatment (chemotherapy, autologous stem cell transplant)

Temozolomide DRUG

Given PO

Also known as: CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temodal, Temodar, Temomedac

Treatment (chemotherapy, autologous stem cell transplant)

Eligibility Criteria

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

You may qualify if:

• Patients with glioblastoma multiforme or gliosarcoma
• The patient or legal guardian must be able to comprehend the informed consent form and sign prior to patient enrollment
• Karnofsky performance status at time of study entry must be \>= 70%
• Life expectancy of \>= 3 months
• Patients must agree to undergo repeat clinical neurological examinations and brain magnetic resonance imaging (MRI) with appropriate contrast after every other cycle of chemotherapy
• White blood cell (WBC) \> 3000/ul
• Absolute neutrophil count (ANC) \> 1500/ul
• Platelets \> 100,000/ul
• Hemoglobin \> 10 gm/100ml
• Total and direct bilirubin \< 1.5 times upper limit of laboratory normal
• Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =\< 3 times upper limit of laboratory normal
• Alkaline phosphatase =\< 3 times upper limit of laboratory normal
• Blood urea nitrogen (BUN) \< 1.5 times upper limit of laboratory normal
• Serum creatinine \< 1.5 times upper limit of laboratory normal
• Left ventricular ejection fraction (LVEF) \>= 40%, however, subjects with a LVEF in the range of 40-49% should have cardiology clearance prior to intervention

You may not qualify if:

• Patients with cardiac insufficiency and a LVEF of \< 40%; history of coronary artery disease or arrhythmia, which has required or requires ongoing treatment
• Patients with active pulmonary infection and/or pulse oximetry \< 90% and a corrected diffusion capacity of the lung for carbon monoxide (DLCO) \< 70% of predicted
• Active systemic infection
• Patients who are human immunodeficiency virus (HIV) positive
• Pregnant or lactating women; a beta-human chorionic gonadotropin (HCG) level will be obtained from women of childbearing potential; fertile men and women should use effective contraception
• Previous chemotherapy for any malignancy including temozolomide, dacarbazine (DTIC) or prior nitrosourea
• Diabetes mellitus
• Bleeding disorder
• Methylated or hypermethylated MGMT promoter status within tumor tissue
• Medical or psychiatric condition which in the opinion of the protocol chairman would compromise the patient's ability to tolerate this protocol
• Prior interstitial radiotherapy, stereotactic or gamma knife surgery or implanted BCNU-wafers

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Adair JE, Johnston SK, Mrugala MM, Beard BC, Guyman LA, Baldock AL, Bridge CA, Hawkins-Daarud A, Gori JL, Born DE, Gonzalez-Cuyar LF, Silbergeld DL, Rockne RC, Storer BE, Rockhill JK, Swanson KR, Kiem HP. Gene therapy enhances chemotherapy tolerance and efficacy in glioblastoma patients. J Clin Invest. 2014 Sep;124(9):4082-92. doi: 10.1172/JCI76739. Epub 2014 Aug 8.

  PMID: 25105369 DERIVED

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

Radiotherapy, Conformal; Carmustine; carmustine, poliferprosan 20 drug combination; Filgrastim; Granulocyte Colony-Stimulating Factor; Radiotherapy, Intensity-Modulated; O(6)-benzylguanine; plerixafor; ferric pyrophosphate; Proton Therapy; Temozolomide

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)

Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Heavy Ion Radiotherapy; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Hans-Peter Kiem, M.D., Ph.D.
• Organization: Fred Hutch Cancer Research Center

hkiem@fredhutch.org

206.667.4425

Study Officials

• Hans-Peter Kiem

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: April 29, 2008
• First Posted: April 30, 2008
• Study Start: February 25, 2009
• Primary Completion: July 6, 2018
• Study Completion: January 20, 2021
• Last Updated: May 18, 2022
• Results First Posted: December 28, 2018

Record last verified: 2022-01

Locations

US (1)