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Brain and Central Nervous System TumorsPhase 1NCT00003567

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

A Phase 1 study testing filgrastim, sargramostim and therapeutic autologous lymphocytes in people with Brain and Central Nervous System Tumors and Lymphoma, run by Case Comprehensive Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
filgrastim, sargramostim and therapeutic autologous lymphocytes
How many people
8 participants
Where
1 siteUnited States
Study dates
May 1999to Feb 2007
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44106-5065

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
filgrastim, sargramostim, therapeutic autologous lymphocytes, O6-benzylguanine, carmustine
Keywords
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
Medical subject headings
Central Nervous System Neoplasms, Lymphoma, Brain Neoplasms, Lymphoma, Follicular, Lymphoma, Non-Hodgkin, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Large-Cell, Immunoblastic, Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • filgrastimBiological

    Patients receive filgrastim (G-CSF) subcutaneously (SC) once daily on days 1-5 (or G-CSF twice daily alone for 4-5 days).

  • sargramostimBiological

    Patients receive sargramostim (GM-CSF) subcutaneously (SC) once daily on days 1-5 (or G-CSF twice daily alone for 4-5 days).

  • therapeutic autologous lymphocytesBiological

  • O6-benzylguanineDrug

    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.

  • carmustineDrug

    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.

  • temozolomideDrug

    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.

  • in vitro-treated peripheral blood stem cell transplantationProcedure or surgery

    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.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Gene transfer expression

    Measured: measured at days 28, 56, 84, and 112, and then every 3 months for 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startMay 1999
  3. Primary completionJan 2007
  4. Study completionFeb 2007

Why it stopped: slow accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00003567
Sponsor's protocol ID
CWRU2Y97
Other IDs
R21CA076192, P30CA043703, CASE-CWRU-2Y97, NCI-T97-0060, CASE-2Y97
Status last verified
Jun 2010
First submitted
1 Nov 1999
Last updated
11 Jun 2010
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing filgrastim, sargramostim and therapeutic autologous lymphocytes in people with Brain and Central Nervous System Tumors and Lymphoma, run by Case Comprehensive Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 11 Jun 2010. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: slow accrual). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Gene transfer expression (time frame: measured at days 28, 56, 84, and 112, and then every 3 months for 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00003567.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2010.

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