NCT00003567

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
8

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started May 1999

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 1999

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

November 1, 1999

Completed
3.2 years until next milestone

First Posted

Study publicly available on registry

January 27, 2003

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2007

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2007

Completed
Last Updated

June 11, 2010

Status Verified

June 1, 2010

Enrollment Period

7.7 years

First QC Date

November 1, 1999

Last Update Submit

June 9, 2010

Conditions

Brain and Central Nervous System TumorsLymphomaUnspecified Adult Solid Tumor, Protocol Specific

Keywords

recurrent adult brain tumoradult brain stem gliomastage IV grade 1 follicular lymphomastage IV grade 2 follicular lymphomastage IV grade 3 follicular lymphomastage IV adult diffuse small cleaved cell lymphomastage IV adult diffuse mixed cell lymphomastage IV adult diffuse large cell lymphomastage IV adult immunoblastic large cell lymphomastage IV adult lymphoblastic lymphomastage IV adult Burkitt lymphomarecurrent grade 1 follicular lymphomarecurrent grade 2 follicular lymphomarecurrent grade 3 follicular lymphomarecurrent adult diffuse small cleaved cell lymphomarecurrent adult diffuse mixed cell lymphomarecurrent adult diffuse large cell lymphomarecurrent adult immunoblastic large cell lymphomarecurrent adult lymphoblastic lymphomarecurrent adult Burkitt lymphomaadult mixed gliomastage IV mantle cell lymphomarecurrent mantle cell lymphomaunspecified adult solid tumor, protocol specificadult anaplastic astrocytomaadult anaplastic oligodendrogliomaadult glioblastomaadult pilocytic astrocytomaadult subependymomaadult anaplastic ependymomaadult myxopapillary ependymomaadult ependymoblastomarecurrent marginal zone lymphomarecurrent small lymphocytic lymphomastage IV small lymphocytic lymphomastage IV marginal zone lymphomaextranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissuenodal marginal zone B-cell lymphomasplenic marginal zone lymphomaadult oligodendrogliomaadult giant cell glioblastomaadult gliosarcomaadult diffuse astrocytoma

Outcome Measures

Primary Outcomes (1)

  • Gene transfer expression

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

Interventions

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

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.

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Study Sites (1)

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

Cleveland, Ohio, 44106-5065, United States

Location

MeSH Terms

Conditions

Central Nervous System NeoplasmsLymphomaBrain NeoplasmsLymphoma, FollicularLymphoma, Non-HodgkinLymphoma, Large B-Cell, DiffuseLymphoma, Large-Cell, ImmunoblasticPrecursor Cell Lymphoblastic Leukemia-LymphomaBurkitt LymphomaGliomaLymphoma, Mantle-CellAstrocytomaOligodendrogliomaGlioblastomaGlioma, SubependymalEpendymomaNeuroectodermal Tumors, PrimitiveLymphoma, B-Cell, Marginal ZoneLeukemia, Lymphocytic, Chronic, B-CellGliosarcoma

Interventions

FilgrastimsargramostimO(6)-benzylguanineCarmustineTemozolomide

Condition Hierarchy (Ancestors)

Nervous System NeoplasmsNeoplasms by SiteNeoplasmsNervous System DiseasesNeoplasms by Histologic TypeLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesBrain DiseasesCentral Nervous System DiseasesLymphoma, B-CellLeukemia, LymphoidLeukemiaHematologic DiseasesEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms, Glandular and EpithelialNeoplasms, Nerve TissueLeukemia, B-CellChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating FactorColony-Stimulating FactorsGlycoproteinsGlycoconjugatesCarbohydratesHematopoietic Cell Growth FactorsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsProteinsBiological FactorsNitrosourea CompoundsUreaAmidesOrganic ChemicalsNitroso CompoundsDacarbazineTriazenesImidazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Stanton L. Gerson, MD

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

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER

Study Record Dates

First Submitted

November 1, 1999

First Posted

January 27, 2003

Study Start

May 1, 1999

Primary Completion

January 1, 2007

Study Completion

February 1, 2007

Last Updated

June 11, 2010

Record last verified: 2010-06

Locations

US(1)