Oblimersen Sodium & Combination Chemotherapy in Treating Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma

NCT00736450 | Terminated Early Phase 1 Results DMC FDA Drug

• 3 other identifiers: 0462-07-FBNCI-2009-01692P30CA036727
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Time to Perform Microarray Study After Receipt of Tissue

  The time from tissue harvest to release of microarray test and IHC assay results will be noted in days.

  Upto 14 days

• Number of Participants With Microarray Testing Results Are Completed Within 7 Days.

  Upto 7 days

Secondary Outcomes (1)

• Efficacy of Treatment, in Terms of Complete Response Rate (Anyone Achieving a CR or Cru)

  End of treatment, an average of 4 months

Study Arms (1)

Arm I

EXPERIMENTAL

See Detailed Description

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

Interventions

oblimersen sodium BIOLOGICAL

Given IV

Also known as: augmerosen, G3139, G3139 bcl-2 antisense oligodeoxynucleotide, Genasense

Arm I

rituximab BIOLOGICAL

Given IV

Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan

Arm I

cyclophosphamide DRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana

Arm I

doxorubicin hydrochloride DRUG

Given IV

Also known as: ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF

Arm I

vincristine sulfate DRUG

Given IV

Also known as: leurocristine sulfate, VCR, Vincasar PFS

Arm I

prednisone DRUG

Given orally

Also known as: DeCortin, Deltra

Arm I

biopsy PROCEDURE

Correlative studies

Also known as: biopsies

Arm I

microarray analysis GENETIC

Correlative studies

Also known as: gene expression profiling

Arm I

immunohistochemistry staining method OTHER

Correlative studies

Also known as: immunohistochemistry

Arm I

gene expression analysis GENETIC

Correlative studies

Arm I

cytogenetic analysis GENETIC

Correlative studies

Arm I

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Nebraska: lead
• National Cancer Institute (NCI): collaborator
• Genta Incorporated: collaborator

Study Sites (2)

Saint Francis Medical Center

Grand Island, Nebraska, 68803, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198-6805, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

oblimersen; Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone; Biopsy; Microarray Analysis; Gene Expression Profiling; Immunohistochemistry; Cytogenetic Analysis

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Microchip Analytical Procedures; Genetic Techniques; Histocytochemistry; Histological Techniques; Immunologic Techniques

Results Point of Contact

• Title: Julie Vose
• Organization: University of Nebraska Medical Center

jmvose@unmc.edu

402-559-3848

Study Officials

• Julie M Vose, MD MBA

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2008
• First Posted: August 15, 2008
• Study Start: July 23, 2008
• Primary Completion: October 9, 2012
• Study Completion: October 9, 2012
• Last Updated: October 24, 2023
• Results First Posted: August 31, 2018

Record last verified: 2023-10

Locations

US (2)