Oblimersen and Gemcitabine in Treating Patients With Advanced Solid Tumor or Lymphoma

This study has been terminated.
(Administratively complete.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00060112
First received: May 6, 2003
Last updated: January 24, 2013
Last verified: January 2013
  Purpose

Drugs used in chemotherapy such as gemcitabine use different ways to stop cancer cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of gemcitabine by making cancer cells more sensitive to the drug. This phase I trial is studying the side effects and best dose of oblimersen and gemcitabine in treating patients with metastatic or unresectable solid tumors or lymphoma


Condition Intervention Phase
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Nodal Marginal Zone B-cell Lymphoma
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Small Lymphocytic Lymphoma
Splenic Marginal Zone Lymphoma
Stage IV Adult Burkitt Lymphoma
Stage IV Adult Diffuse Large Cell Lymphoma
Stage IV Adult Diffuse Mixed Cell Lymphoma
Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
Stage IV Adult Hodgkin Lymphoma
Stage IV Adult Immunoblastic Large Cell Lymphoma
Stage IV Adult Lymphoblastic Lymphoma
Stage IV Adult T-cell Leukemia/Lymphoma
Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Grade 3 Follicular Lymphoma
Stage IV Mantle Cell Lymphoma
Stage IV Marginal Zone Lymphoma
Stage IV Small Lymphocytic Lymphoma
Unspecified Adult Solid Tumor, Protocol Specific
Biological: oblimersen sodium
Drug: gemcitabine hydrochloride
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Oblimersen (Genasense™, G3139) in Combination With Gemcitabine in Advanced Malignancies

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • MTD defined as the dose level at which less than 2 out of 6 patients experience DLT assessed using NCI CTC version 2.0 [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    Descriptive statistics will be employed in the analysis of all safety and laboratory observations.


Secondary Outcome Measures:
  • Pharmacokinetics [ Time Frame: Pre-dose, 4, 8, 12, 24, 48, 72, 96, 120, 121.67, 126, and 129 hours ] [ Designated as safety issue: No ]
    Peak concentration and area under the concentration time curves of gemcitabine triphosphate will be will be utilized to assess the pharmacodynamic relationship of gemcitabine triphosphate concentration to bivariate toxicity and tumor responses using logistic regression analysis.


Enrollment: 15
Study Start Date: March 2003
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (oblimersen sodium and gemcitabine hydrochloride)
Patients receive oblimersen IV continuously on days 1-5 and gemcitabine IV over 2-3 hours on day 5. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.
Biological: oblimersen sodium
Given IV
Other Names:
  • augmerosen
  • G3139
  • G3139 bcl-2 antisense oligodeoxynucleotide
  • Genasense
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose and dose-limiting toxicity of oblimersen and gemcitabine in patients with advanced solid tumor or lymphoma.

II. Determine the effect of oblimersen on the pharmacokinetics and pharmacodynamics of gemcitabine in these patients.

III. Determine the toxic effects of this regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive oblimersen IV continuously on days 1-5 and gemcitabine IV over 2-3 hours on day 5. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of oblimersen and gemcitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 10 additional patients receive treatment at the MTD.

PROJECTED ACCRUAL: Approximately 15 patients will be accrued for this study within 6-8 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed malignancy for which there is no standard or effective curative or palliative therapy

    • Solid tumors and lymphoma allowed
    • Metastatic or unresectable disease
  • Measurable or evaluable nonmeasurable disease

    • Evaluable nonmeasurable disease includes ascites, pleural/pericardial effusions, lymphangitis cutis/pulmonis, inflammatory breast disease, abdominal masses not followed by CT scan or MRI, or cystic lesions
    • Disease characterized by elevated serum tumor marker alone is allowed
  • No known brain metastases
  • Performance status - ECOG 0-2
  • Performance status - Karnofsky 60-100%
  • More than 3 months
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Bilirubin no greater than 1.5 mg/dL
  • AST and ALT no greater than 2.5 times upper limit of normal
  • No history of portal hypertension
  • No history of cirrhosis or hepatitis
  • No radiographic evidence of cirrhosis and/or varices
  • Creatinine normal
  • Creatinine clearance at least 60 mL/min
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No prior allergic reaction attributed to compounds of similar chemical or biological composition to oblimersen or other study agents
  • No other concurrent uncontrolled illness that would preclude study participation
  • No ongoing or active infection
  • No psychiatric illness or social situation that would preclude study compliance
  • No concurrent prophylactic colony-stimulating factors such as filgrastim (G-CSF) or sargramostim (GM-CSF)
  • Concurrent interventional growth factors allowed

    • No growth factor administration within 24 hours before study chemotherapy
  • Concurrent epoetin alfa allowed
  • No more than 3 prior chemotherapy regimens
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
  • More than 2 weeks since prior hormonal therapy
  • Concurrent megestrol for anorexia/cachexia allowed
  • No prior pelvic or whole abdominal radiotherapy
  • More than 4 weeks since prior radiotherapy
  • More than 4 weeks since prior major surgery
  • Recovered from prior therapy
  • More than 4 weeks since prior investigational therapy
  • No prior oblimersen
  • No other concurrent investigational agents
  • No other concurrent anticancer therapy
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00060112

Locations
United States, California
Stanford University
Stanford, California, United States, 94305
Sponsors and Collaborators
Investigators
Principal Investigator: Branimir (Brandy) Sikic Stanford University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00060112     History of Changes
Other Study ID Numbers: NCI-2012-02531, SUMC-78808, CDR0000299507
Study First Received: May 6, 2003
Last Updated: January 24, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Burkitt Lymphoma
Hodgkin Disease
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, Mantle-Cell
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
DNA Virus Infections
Epstein-Barr Virus Infections
Herpesviridae Infections
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Leukemia, Lymphoid
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Experimental
Tumor Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on October 30, 2014