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
Conditions
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.
Interventions
BIOLOGICALoblimersen sodium
Given IV
BIOLOGICALrituximab
Given IV
DRUGcyclophosphamide
Given IV
DRUGdoxorubicin hydrochloride
Given IV
DRUGvincristine sulfate
Given IV
DRUGprednisone
Given orally
PROCEDUREbiopsy
Correlative studies
GENETICmicroarray analysis
Correlative studies
OTHERimmunohistochemistry staining method
Correlative studies
GENETICgene expression analysis
Correlative studies
GENETICcytogenetic analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Genta Incorporated
University of Nebraska
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Perform Microarray Study After Receipt of Tissue | 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. | Upto 7 days | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Treatment, in Terms of Complete Response Rate (Anyone Achieving a CR or Cru) | 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 |
Countries
United States
Participant flow
Pre-assignment details
Of the 37 subjects consented, 19 were Not ABC gene type positive so were removed from the study. Of the 18 remaining eligible, 4 patients opted for standard of care and withdrew from the study. 13 subjects had microarray analysis conducted with tissue.
Participants by arm
| Arm | Count |
|---|---|
| Arm I Patients in this study who are found to have the Activated B-Cell (ABC) type after gene expression profiling or Immunohistochemistry (IHC) staining will receive combination chemotherapy with the standard CHOP-R with Genasense (oblimersen) (anti-bcl2 oligonucleotide).
oblimersen sodium: Given IV
rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate: Given IV
prednisone: Given orally | 37 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Not ABC gene eligible | 19 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Arm I |
|---|---|
| Age, Continuous | 53 years |
| Region of Enrollment United States | 37 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 14 |
| other Total, other adverse events | 12 / 14 |
| serious Total, serious adverse events | 2 / 14 |
Outcome results
Primary
Number of Participants With Microarray Testing Results Are Completed Within 7 Days.
Time frame: Upto 7 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm I | Number of Participants With Microarray Testing Results Are Completed Within 7 Days. | results within 7 days or less | 11 Participants |
| Arm I | Number of Participants With Microarray Testing Results Are Completed Within 7 Days. | results in more than 7 days | 2 Participants |
Primary
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.
Time frame: Upto 14 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm I | Time to Perform Microarray Study After Receipt of Tissue | 4.4 days |
Secondary
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
Time frame: End of treatment, an average of 4 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm I | Efficacy of Treatment, in Terms of Complete Response Rate (Anyone Achieving a CR or Cru) | complete response | 12 Participants |
| Arm I | Efficacy of Treatment, in Terms of Complete Response Rate (Anyone Achieving a CR or Cru) | partial response | 1 Participants |