Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Gene Therapy and Chemotherapy in Treating Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00003567
Recruitment Status : Terminated (slow accrual)
First Posted : January 27, 2003
Last Update Posted : June 11, 2010
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
Case Comprehensive Cancer Center

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:

RATIONALE: Gene therapy may improve the body's ability to fight cancer or make the cancer more sensitive to chemotherapy. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase I trial is studying the side effects and best dose of gene therapy together with chemotherapy in treating patients with advanced solid tumors or non-Hodgkin's lymphoma.


Condition or disease Intervention/treatment Phase
Brain and Central Nervous System Tumors Lymphoma Unspecified Adult Solid Tumor, Protocol Specific Biological: filgrastim Biological: sargramostim Biological: therapeutic autologous lymphocytes Drug: O6-benzylguanine Drug: carmustine Drug: temozolomide Procedure: in vitro-treated peripheral blood stem cell transplantation Phase 1

Detailed Description:

OBJECTIVES:

  • Evaluate the feasibility of introducing and expressing mutant MGMT-G156A cDNA in hematopoietic progenitors taken from patients with advanced solid tumors (including gliomas) or non-Hodgkin's lymphoma using a safety modified retroviral vector MFG.
  • Determine the toxicity associated with reinfusion of ex vivo-transduced hematopoietic stem cells into these patients, including the detection of replication competent retrovirus.
  • Evaluate the feasibility of identifying mutant MGMT-G156A-transduced and O6-benzylguanine (BG)- and temzolomide-resistant hematopoietic and stromal progenitors from the bone marrow of these patients.
  • Evaluate the feasibility of in vivo enrichment of the transduced hematopoietic progenitors in patients treated with BG and temzolomide.
  • Evaluate the toxicity of this regimen in these patients.
  • Determine the antitumor effect of this regimen in these patients.

OUTLINE: This is a dose-escalation study of CD34 stem cells and carmustine.

After a negative bone marrow sampling, patients receive sargramostim (GM-CSF) and filgrastim (G-CSF) subcutaneously (SC) once daily on days 1-5 (or G-CSF twice daily alone for 4-5 days). Peripheral blood progenitor cells are collected 24 hours after the last dose of growth factor injection on day 5 and also on day 6, if necessary. The CD34 positive stem cells are then infected by the retroviral mutant MGMT-G156A ex vivo.

Patients receive O6-benzylguanine (BG) IV over 1 hour followed by carmustine IV over 1 hour every 6 weeks for 5 courses, assuming recovery of peripheral blood counts. Approximately 72 hours after the end of the first course of chemotherapy, patients receive reinfusion of retrovirally-transduced hematopoietic stem cells over 5-10 minutes. Four weeks after the completion of BG and carmustine, patients receive BG IV over 1 hour followed by temozolomide IV over 1 hour every 4 weeks for up to 5 courses, in the absence of hematologic toxicity. Patients with responding disease may continue to receive BG and temzolomide in the absence of disease progression or unacceptable toxicity provided other phase II studies indicate the safety of more than 5 courses.

Cohorts of 3-6 patients receive escalating numbers of CD34 stem cells targeted for retroviral infection and escalating doses of carmustine.

Patients are followed monthly for 2 months, every 4 months for 8 months, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 12-18 patients will be accrued for this study.

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Mutant MGMT Gene Transfer Into Human Hematopoietic Progenitors to Protect Hematopoiesis During O6-Benzylguanine (BG, NSC 637037) and Carmustine Followed by Temozolomide Therapy of Advanced Solid Tumors
Study Start Date : May 1999
Actual Primary Completion Date : January 2007
Actual Study Completion Date : February 2007

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Intervention Details:
  • Biological: filgrastim
    Patients receive filgrastim (G-CSF) subcutaneously (SC) once daily on days 1-5 (or G-CSF twice daily alone for 4-5 days).
  • Biological: sargramostim
    Patients receive sargramostim (GM-CSF) subcutaneously (SC) once daily on days 1-5 (or G-CSF twice daily alone for 4-5 days).
  • Biological: therapeutic autologous lymphocytes
  • Drug: O6-benzylguanine
    Patients receive O6-benzylguanine (BG) IV over 1 hour every 6 weeks for 5 courses. Four weeks after the completion of BG and carmustine, patients receive BG IV over 1 hour every 4 weeks for up to 5 courses, in the absence of hematologic toxicity. Patients with responding disease may continue to receive BG and temzolomide in the absence of disease progression or unacceptable toxicity.
  • Drug: carmustine
    Patients receive carmustine IV over 1 hour every 6 weeks for 5 courses.Cohorts of 3-6 patients receive escalating numbers of CD34 stem cells targeted for retroviral infection and escalating doses of carmustine.
  • Drug: temozolomide
    Four weeks after the completion of BG and carmustine, patients receive temozolomide IV over 1 hour every 4 weeks for up to 5 courses, in the absence of hematologic toxicity. Patients with responding disease may continue to receive BG and temzolomide in the absence of disease progression or unacceptable toxicity.
  • Procedure: in vitro-treated peripheral blood stem cell transplantation
    Approximately 72 hours after the end of the first course of chemotherapy, patients receive reinfusion of retrovirally-transduced hematopoietic stem cells over 5-10 minutes. Cohorts of 3-6 patients receive escalating numbers of CD34 stem cells targeted for retroviral infection and escalating doses of carmustine.

Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Gene transfer expression [ Time Frame: measured at days 28, 56, 84, and 112, and then every 3 months for 1 year ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • One of the following histologically confirmed diseases for which no curative surgical, radiotherapy, or chemotherapy programs are available and standard therapy offers, at best, a modest clinical benefit

    • Solid tumors
    • Gliomas
    • Non-Hodgkin's lymphoma
  • Primary and metastatic CNS malignancies are eligible
  • Evaluable or measurable disease
  • CD34 count at least 2.0 cells/μL

  • No bone marrow involvement

    • Histologically negative bone marrow biopsy

PATIENT CHARACTERISTICS:

Age:

  • 18 to 70

Performance status:

  • ECOG 0-2

Life expectancy:

  • At least 12 weeks

Hematopoietic:

  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 8.5 g/dL

Hepatic:

  • Bilirubin no greater than 1.5 mg/dL
  • AST and ALT less than 2.5 times normal
  • Prothrombin time less than 1.2 times normal

Renal:

  • Creatinine no greater than 2.0 mg/dL

Cardiovascular:

  • No acute cardiac disease by EKG

Pulmonary:

  • No symptomatic pulmonary disease

Other:

  • HIV negative
  • No other severe comorbid conditions
  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for 2 months after study completion

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • See Chemotherapy
  • No prior hematopoietic stem cell transplantation

Chemotherapy:

  • No prior high-dose chemotherapy
  • Prior adjuvant chemotherapy allowed

Endocrine therapy:

  • Not specified

Radiotherapy:

  • No prior radiotherapy to 25% or more of bone marrow

Surgery:

  • Not specified

Other:

  • At least 4 weeks since prior myelosuppressive therapy
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00003567


Locations
Layout table for location information
United States, Ohio
Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
Sponsors and Collaborators
Case Comprehensive Cancer Center
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Study Chair: Stanton L. Gerson, MD Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Stanton L. Gerson, MD, Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00003567    
Other Study ID Numbers: CWRU2Y97
R21CA076192 ( U.S. NIH Grant/Contract )
P30CA043703 ( U.S. NIH Grant/Contract )
CASE-CWRU-2Y97 ( Other Identifier: Case Comprehensive Cancer Center )
NCI-T97-0060
CASE-2Y97 ( Other Identifier: Case Comprehensive Cancer Center )
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: June 11, 2010
Last Verified: June 2010
Keywords provided by Case Comprehensive Cancer Center:
recurrent adult brain tumor
adult brain stem glioma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV adult Burkitt lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
 recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
adult mixed glioma
stage IV mantle cell lymphoma
recurrent mantle cell lymphoma
unspecified adult solid tumor, protocol specific
adult anaplastic astrocytoma
adult anaplastic oligodendroglioma
adult glioblastoma
adult pilocytic astrocytoma
adult subependymoma
adult anaplastic ependymoma
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Neoplasms
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site
Nervous System Diseases
 Temozolomide
Carmustine
O(6)-benzylguanine
Sargramostim
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors