Oblimersen Sodium & Combination Chemotherapy in Treating Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma
Primary Purpose
Contiguous Stage II Adult Diffuse Large Cell Lymphoma, Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma, Stage I Adult Diffuse Large Cell Lymphoma
Status
Terminated
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
oblimersen sodium
rituximab
cyclophosphamide
doxorubicin hydrochloride
vincristine sulfate
prednisone
biopsy
microarray analysis
immunohistochemistry staining method
gene expression analysis
cytogenetic analysis
Sponsored by
About this trial
This is an interventional treatment trial for Contiguous Stage II Adult Diffuse Large Cell Lymphoma
Eligibility 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
Sites / Locations
- Saint Francis Medical Center
- University of Nebraska Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Arm I
Arm Description
See Detailed Description
Outcomes
Primary Outcome Measures
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.
Number of Participants With Microarray Testing Results Are Completed Within 7 Days.
Secondary Outcome Measures
Efficacy of Treatment, in Terms of Complete Response Rate (Anyone Achieving a CR or Cru)
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
Full Information
NCT ID
NCT00736450
First Posted
August 14, 2008
Last Updated
October 20, 2023
Sponsor
University of Nebraska
Collaborators
National Cancer Institute (NCI), Genta Incorporated
1. Study Identification
Unique Protocol Identification Number
NCT00736450
Brief Title
Oblimersen Sodium & Combination Chemotherapy in Treating Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma
Official Title
Investigator Initiated Pilot Study of Microarray Directed Therapy for Diffuse Large B-cell Lymphoma Using Genasense With CHOP-R
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Terminated
Why Stopped
Manufacturer is no longer making the drug.
Study Start Date
July 23, 2008 (Actual)
Primary Completion Date
October 9, 2012 (Actual)
Study Completion Date
October 9, 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Nebraska
Collaborators
National Cancer Institute (NCI), Genta Incorporated
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm I
Arm Type
Experimental
Arm Description
See Detailed Description
Intervention Type
Biological
Intervention Name(s)
oblimersen sodium
Other Intervention Name(s)
augmerosen, G3139, G3139 bcl-2 antisense oligodeoxynucleotide, Genasense
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
rituximab
Other Intervention Name(s)
IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
CPM, CTX, Cytoxan, Endoxan, Endoxana
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
doxorubicin hydrochloride
Other Intervention Name(s)
ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
vincristine sulfate
Other Intervention Name(s)
leurocristine sulfate, VCR, Vincasar PFS
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
prednisone
Other Intervention Name(s)
DeCortin, Deltra
Intervention Description
Given orally
Intervention Type
Procedure
Intervention Name(s)
biopsy
Other Intervention Name(s)
biopsies
Intervention Description
Correlative studies
Intervention Type
Genetic
Intervention Name(s)
microarray analysis
Other Intervention Name(s)
gene expression profiling
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
immunohistochemistry staining method
Other Intervention Name(s)
immunohistochemistry
Intervention Description
Correlative studies
Intervention Type
Genetic
Intervention Name(s)
gene expression analysis
Intervention Description
Correlative studies
Intervention Type
Genetic
Intervention Name(s)
cytogenetic analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Time to Perform Microarray Study After Receipt of Tissue
Description
The time from tissue harvest to release of microarray test and IHC assay results will be noted in days.
Time Frame
Upto 14 days
Title
Number of Participants With Microarray Testing Results Are Completed Within 7 Days.
Time Frame
Upto 7 days
Secondary Outcome Measure Information:
Title
Efficacy of Treatment, in Terms of Complete Response Rate (Anyone Achieving a CR or Cru)
Description
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
Time Frame
End of treatment, an average of 4 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julie M Vose, MD MBA
Organizational Affiliation
University of Nebraska
Official's Role
Principal Investigator
Facility Information:
Facility Name
Saint Francis Medical Center
City
Grand Island
State/Province
Nebraska
ZIP/Postal Code
68803
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198-6805
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Oblimersen Sodium & Combination Chemotherapy in Treating Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma
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