Oblimersen, Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Treating Patients With Stage II, Stage III, or Stage IV Diffuse Large B-Cell Lymphoma
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Purpose
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
| Condition | Intervention | Phase |
|---|---|---|
|
Lymphoma |
Biological: oblimersen sodium Biological: rituximab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: vincristine sulfate |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Primary Purpose: Treatment |
| Official Title: | A Phase I Study Of G3139 Antisense Oligonucleotide (Oblimersen) In Combination With CHOP And Rituximab In Untreated Advanced Stage Diffuse Large B Cell Lymphoma |
| Study Start Date: | July 2003 |
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.
Eligibility| Ages Eligible for Study: | 19 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| United States, California | |
| Stanford Cancer Center at Stanford University Medical Center | |
| Stanford, California, United States, 94305 | |
| Canada, British Columbia | |
| British Columbia Cancer Agency - Centre for the Southern Interior | |
| Kelowna, British Columbia, Canada, V1Y 5L3 | |
| Fraser Valley Cancer Centre at British Columbia Cancer Agency | |
| Surrey, British Columbia, Canada, V3V 1Z2 | |
| British Columbia Cancer Agency - Vancouver Cancer Centre | |
| Vancouver, British Columbia, Canada, V5Z 4E6 | |
| Study Chair: | Richard J. Klasa, MD | British Columbia Cancer Agency |
More Information
Additional Information:
No publications provided
| ClinicalTrials.gov Identifier: | NCT00070083 History of Changes |
| Other Study ID Numbers: | CDR0000329985, BCCA-NCI-5818, NCI-5818 |
| Study First Received: | October 3, 2003 |
| Last Updated: | April 4, 2009 |
| Health Authority: | United States: Federal Government |
Keywords provided by National Cancer Institute (NCI):
|
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 |
Additional relevant MeSH terms:
|
Lymphoma Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Lymphoma, Non-Hodgkin Cyclophosphamide Rituximab Doxorubicin Prednisone Vincristine |
Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antirheumatic Agents Therapeutic Uses Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antibiotics, Antineoplastic Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists |
ClinicalTrials.gov processed this record on May 19, 2013