Oblimersen Sodium and Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage I, Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma

This study has been terminated.
(Manufacturer is no longer making the drug.)
Sponsor:
Collaborators:
Genta Incorporated
Information provided by (Responsible Party):
Julie M Vose, MD, University of Nebraska
ClinicalTrials.gov Identifier:
NCT00736450
First received: August 14, 2008
Last updated: October 11, 2012
Last verified: October 2012
  Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Oblimersen sodium may help chemotherapy work better by making cancer cells more sensitive to the drugs. Giving oblimersen sodium together with combination chemotherapy may kill more cancer cells. PURPOSE: This clinical trial is studying the side effects of giving oblimersen sodium together with combination chemotherapy and to see how well it works in treating patients with newly diagnosed stage I, stage II, stage III, or stage IV diffuse large B-cell lymphoma


Condition Intervention
Contiguous Stage II Adult Diffuse Large Cell Lymphoma
Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma
Stage I Adult Diffuse Large Cell Lymphoma
Stage III Adult Diffuse Large Cell Lymphoma
Stage IV Adult Diffuse Large Cell Lymphoma
Biological: oblimersen sodium
Biological: rituximab
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: vincristine sulfate
Drug: prednisone
Procedure: biopsy
Genetic: microarray analysis
Other: immunohistochemistry staining method
Genetic: gene expression analysis
Genetic: cytogenetic analysis

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Investigator Initiated Pilot Study of Microarray Directed Therapy for Diffuse Large B-cell Lymphoma Using Genasense With CHOP-R

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • Feasibility of performing an AFFYmetrix microarray study [ Time Frame: Within 7 working days of receipt of adequate tissue samples at the University of Nebraska Medical Center (UNMC) ] [ Designated as safety issue: No ]
  • Rate of rapid turn around of the microarray testing results, as assessed by the proportion of patients whose microarray and IHC tests are completed [ Time Frame: Within 7 working days of receipt of adequate tissue samples at the University of Nebraska Medical Center (UNMC) ] [ Designated as safety issue: No ]
  • Efficacy of treatment, in terms of complete response rate (anyone achieving a CR or Cru) [ Time Frame: End of treatment ] [ Designated as safety issue: No ]
  • Toxicity as assessed by NCI CTCAE v3.0 [ Time Frame: During each cycle ] [ Designated as safety issue: Yes ]

Enrollment: 37
Study Start Date: July 2008
Estimated Study Completion Date: October 2022
Estimated Primary Completion Date: October 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
See Detailed Description
Biological: oblimersen sodium
Given IV
Other Names:
  • augmerosen
  • G3139
  • G3139 bcl-2 antisense oligodeoxynucleotide
  • Genasense
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: prednisone
Given orally
Other Names:
  • DeCortin
  • Deltra
Procedure: biopsy
Correlative studies
Other Name: biopsies
Genetic: microarray analysis
Correlative studies
Other Name: gene expression profiling
Other: immunohistochemistry staining method
Correlative studies
Other Name: immunohistochemistry
Genetic: gene expression analysis
Correlative studies
Genetic: cytogenetic analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES: I. To assess the feasibility and determine the rate of rapid turn around, that is within 7 working days of receipt of adequate tissue at UNMC for a AFFYmetrix microarray study of newly diagnosed patients with Diffuse Large B-cell Lymphoma (DLBCL) who will then receive treatment on this protocol. II. To evaluate efficacy (complete response rate) of Genasense (antisense bcl-2) given in addition to standard cyclophosphamide, vincristine, doxorubicin, and prednisone -rituximab (CHOP-R) to newly diagnosed patients with DLBCL who are found to have the ABC type after gene expression profiling or IHC as compared to newly diagnosed patients with DLBCL who do not express the ABC type that go on to receive standard CHOP-R (control). III. To evaluate the toxicity of Genasense (antisense bcl-2) given in addition to standard cyclophosphamide, vincristine, doxorubicin, and prednisone -rituximab (CHOP-R) for newly diagnosed patients with DLBCL who are found to have the ABC type after gene expression profiling. OUTLINE: Patients with diffuse large B-cell lymphoma (DLBCL) that expresses ABC type proceed to treatment in group I. Patients with DLBCL that does not express ABC type proceed to treatment in group II. GROUP I (oblimersen sodium and standard CHOP-R): Patients receive oblimersen sodium IV continuously on days 1-7. Patients also receive CHOP-R comprising rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 5 and prednisone orally on days 5-10. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. GROUP II (standard CHOP-R alone): Patients receive CHOP-R comprising rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 1 and prednisone orally on days 1-5. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed periodically.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Newly diagnosed patients with Diffuse Large B-cell Lymphoma (DLBCL) (any stage) OR composite lymphoma with >= 50% DLBCL
  • Adequate diagnostic tissue for microarray gene expression analysis or IHC analysis
  • Karnofsky Performance Status >= 70 (ECOG 0, 1)
  • No prior chemotherapy (with the exception of 1 cycle CHOP-R based on current diagnosis, clinical condition, and availability/feasibility of initiating Genasense), immunotherapy, radiotherapy, or investigational therapies for NHL; steroid therapy is allowed only if required for maintenance of another chronic disease (e.g., rheumatoid arthritis)
  • Patients aged >= 60 years, or patients with a history of coronary artery disease, congestive heart failure, hypertension, diabetes, or hyperlipidemia must have an estimated ejection fraction >= 0.45 (45%) by MUGA or echocardiography, performed within two months of study entry
  • Patients must be willing to give written informed consent, and sign an institutionally approved consent form prior to initiating genasense or any study related activities (i.e., Genasense & microarray)
  • Females of childbearing potential must have a negative serum pregnancy test prior to enrollment in the study
  • Adequate venous access for 7-day continuous infusion
  • Patients without evidence of severe organ dysfunction as determined within two weeks of 1st cycle of CHOP-R: 1) Hemoglobin > 8 g/dl; 2) Absolute neutrophil count > 1000/; 3) Platelets > 100,000 (lower blood counts may be acceptable if due to lymphoma after review with principal investigator); 4) Creatinine =< 2.0 mg/dL (unless due to NHL); 5) Bilirubin =< 2.0 mg/dL; 6) AST =< 3 x upper normal; 7) ALP =< 3 x upper normal (unless due to NHL)
  • Men and women of reproductive potential must agree to use TWO of the following forms of birth control every time they have sex throughout the study and for up to 3 months following discontinuation of study drug: hormonal birth control methods, condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicidal, IUD, or surgical sterilization while participating in this study

Exclusion Criteria:

  • Significant medical disease other than cancer including: 1) Any bleeding or coagulation disorder including a history of autoimmune hemolytic anemia or autoimmune thrombocytopenia; 2) Severe pulmonary disease; 3) Uncontrolled congestive heart failure; 4) New York Heart Association class III or IV disease; 5) Uncontrolled seizure disorder; and 6) Active infections
  • Less than 3 weeks from prior major surgery
  • Prior organ allograft
  • Known HIV infection (due to expected frequent occurrence of myelo-suppression and immunosuppression)
  • Women who are pregnant (confirmed by a serum pregnancy test in females of reproductive potential) or breast-feeding (women of child-bearing potential and sexually active males must be advised to take precautions to prevent pregnancy during treatment or remain abstinent)
  • Women of child-bearing potential and sexually active males must be advised to take precautions to prevent pregnancy during treatment (unless the subject or subject's partner(s) is sterile, i.e., women who have had a hysterectomy or have been post-menopausal for at least twelve consecutive months) or remain abstinent
  • Known hypersensitivity to phosphorothiate-containing oligonucleotides
  • Concurrent investigational, corticosteroid therapy or any other anti-cancer treatments (such as chemotherapy, radiation, biologic or investigational therapies) while receiving protocol therapy; other than one cycle CHOP-R allowed based on current diagnosis, clinical condition, and availability/feasibility of initiating Genasense; other than chronic steroid use for another indication (For stage I/II or as clinically indicated- involved field irradiation as per standard practice is accepted)
  • Other investigational drug therapy within 30 days of study entry
  • Secondary leukemia or history of antecedent hematologic disorder
  • History of second cancer (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for three or more years)
  • No active CNS disease defined as symptomatic meningeal lymphoma or known CNS parenchymal lymphoma
  • Concomitant anticoagulant therapy is not permitted (with the exception of 1 mg/day of warfarin for central line prophylaxis)
  • Known hypersensitivity to G3139 (Genasense) or R-CHOP
  • Neurologic disorders, overt psychosis, mental disability or evidence of limited capacity to provide fully informed consent or cooperation with the complexities of the treatment program
  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: NCT00736450

Locations
United States, Nebraska
Saint Francis Medical Center
Grand Island, Nebraska, United States, 68803
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-6805
Sponsors and Collaborators
University of Nebraska
Genta Incorporated
Investigators
Principal Investigator: Julie Vose University of Nebraska
  More Information

No publications provided

Responsible Party: Julie M Vose, MD, Neumann M. and Mildred E. Harris Professor, Chief, Division of Hematology/Oncology, University of Nebraska
ClinicalTrials.gov Identifier: NCT00736450     History of Changes
Other Study ID Numbers: 462-07, NCI-2009-01692, P30CA036727
Study First Received: August 14, 2008
Last Updated: October 11, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Cyclophosphamide
Rituximab
Doxorubicin
Prednisone
Vincristine
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on July 20, 2014