Oblimersen, Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Treating Patients With Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, use different ways to stop cancer cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of a chemotherapy drug by making cancer cells more sensitive to the drug. Combining oblimersen with rituximab and combination chemotherapy may kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of oblimersen when given together with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in treating patients with stage II, stage III, or stage IV large B-cell lymphoma

Detailed Description
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OBJECTIVES: Primary Determine the feasibility and safety of oblimersen administered in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, in terms of short-term and long-term toxicity, in patients with previously untreated stage III or IV or extensive or bulky stage II diffuse large B-cell lymphoma. Determine the maximum tolerated dose of oblimersen administered with this regimen in these patients. Secondary Determine the remission rate and failure-free, progression-free, and overall survival of patients treated with this regimen. OUTLINE: This is a nonrandomized, non-blinded, multicenter, dose-escalation study of oblimersen. Patients receive CHOP-R* therapy comprising cyclophosphamide IV over 15-45 minutes, doxorubicin IV over 5-10 minutes, vincristine IV, and rituximab IV over 30-90 minutes on day 1 and oral prednisone on days 1-5. Patients also receive oblimersen IV continuously on days -4 to 3. Treatment repeats every 21 days for 6-8 courses in the absence of disease progression or unacceptable toxicity. Patients who discontinue treatment due to unacceptable toxicity to oblimersen may continue to receive standard therapy comprising CHOP-R. NOTE: *Patients treated at the British Columbia Cancer Agency receive cyclophosphamide, doxorubicin, vincristine, and rituximab on days 1 and 2 and prednisone as above. Cohorts of 3-6 patients receive escalating doses of oblimersen until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, at least 10 patients are treated at that dose level. Patients are followed every 3 months for 2 years, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 19-28 patients will be accrued for this study within 5-10 months.

Official Title
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A Phase I Study Of G3139 Antisense Oligonucleotide (Oblimersen) In Combination With CHOP And Rituximab In Untreated Advanced Stage Diffuse Large B Cell Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: oblimersen sodium
* Biological: rituximab
* Drug: cyclophosphamide
* Drug: doxorubicin hydrochloride
* Drug: prednisone
* Drug: vincristine sulfate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed* CD20+ diffuse large B-cell lymphoma, including any of the following stages: Extensive stage II (not radio-encompassable within a single involved field or not a candidate for brief chemotherapy and radiotherapy) Bulky stage II (any single mass greater than 10 cm) Stage III Stage IV NOTE: *Confirmed by tissue biopsy Previously untreated disease Measurable disease At least 2 cm by imaging studies Circulating lymphoma cells no greater than 5,000/mm^3 No history of other lymphoproliferative disorder No history of indolent lymphoma No T-cell lymphoma No CNS involvement No post-transplantation lymphoproliferative disorder PATIENT CHARACTERISTICS: Age 19 and over Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic Absolute neutrophil count at least 1,500/mm^3 (unless due to bone marrow involvement with lymphoma) Platelet count at least 100,000/mm^3 (unless due to splenomegaly or bone marrow involvement with lymphoma) Hepatic Bilirubin no greater than 3 mg/dL (unless due to lymphoma) No known hepatitis B virus Renal Creatinine no greater than 2 mg/dL (unless due to lymphoma) Cardiovascular No cardiac contraindication to doxorubicin therapy (e.g., abnormal contractility on echocardiography) History of cardiac disease allowed provided ejection fraction is normal Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Adequate venous access HIV negative No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer, localized basal cell or squamous cell skin cancer, or curatively treated carcinoma in situ of the cervix No neurological contraindication to vincristine (e.g., peripheral neuropathy) No active systemic infection No medical condition that would compromise study treatment, add toxicity, or impair assessment PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior systemic chemotherapy Endocrine therapy Not specified Radiotherapy No prior radiotherapy Prior radiotherapy for localized basal cell or squamous cell skin cancer used with curative intent allowed Surgery Not specified

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: oblimersen sodium|nan|
|Biological: rituximab|nan|
|Drug: cyclophosphamide|nan|
|Drug: doxorubicin hydrochloride|nan|
|Drug: prednisone|nan|
|Drug: vincristine sulfate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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contiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma