Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00736450
Recruitment Status : Terminated (Manufacturer is no longer making the drug.)
First Posted : August 15, 2008
Results First Posted : August 31, 2018
Last Update Posted : August 31, 2018
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Genta Incorporated
Information provided by (Responsible Party):
Julie M Vose, MD, University of Nebraska

Tracking Information
First Submitted Date  ICMJE August 14, 2008
First Posted Date  ICMJE August 15, 2008
Results First Submitted Date  ICMJE January 30, 2018
Results First Posted Date  ICMJE August 31, 2018
Last Update Posted Date August 31, 2018
Study Start Date  ICMJE July 2008
Actual Primary Completion Date September 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 3, 2018)
  • Time to Perform Microarray Study After Receipt of Tissue [ Time Frame: Upto 14 days ]
    The time from tissue harvest to release of microarray test and IHC assay results will be noted in days.
  • Number of Participants With Microarray Testing Results Are Completed Within 7 Days. [ Time Frame: Upto 7 days ]
Original Primary Outcome Measures  ICMJE
 (submitted: August 14, 2008)
  • Feasibility of performing an AFFYmetrix microarray study
  • Rate of rapid turn around of the microarray testing results, as assessed by the proportion of patients whose microarray and IHC tests are completed within 7 working days of receipt of adequate tissue samples at the University of Nebraska Medical Cen ...
  • Efficacy of treatment, in terms of complete response rate
  • Toxicity as assessed by NCI CTCAE v3.0
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 3, 2018)
Efficacy of Treatment, in Terms of Complete Response Rate (Anyone Achieving a CR or Cru) [ Time Frame: End of treatment, an average of 4 months ]
Response criteria are the recommendations of the International Harmonization Project's update to the International Working Group guidelines. Complete response (CR) is defined as disappearance of all evidence of disease; Partial response (PR) is defined as regression of measurable disease and no new sites
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE Investigator Initiated Pilot Study of Microarray Directed Therapy for Diffuse Large B-cell Lymphoma Using Genasense With CHOP-R
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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • 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
Study Arms  ICMJE Experimental: Arm I
See Detailed Description
Interventions:
  • 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: October 11, 2012)
37
Original Estimated Enrollment  ICMJE
 (submitted: August 14, 2008)
70
Actual Study Completion Date  ICMJE October 2012
Actual Primary Completion Date September 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 19 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00736450
Other Study ID Numbers  ICMJE 462-07
NCI-2009-01692 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
P30CA036727 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Julie M Vose, MD, University of Nebraska
Study Sponsor  ICMJE University of Nebraska
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • Genta Incorporated
Investigators  ICMJE
Principal Investigator: Julie Vose University of Nebraska
PRS Account University of Nebraska
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP