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

Sponsor:	British Columbia Cancer Agency
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00070083

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 I

Study Type:	Interventional
Study Design:	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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Cyclophosphamide Prednisone Vincristine Doxorubicin Doxorubicin hydrochloride Myocet Rituximab Oblimersen sodium Vincristine sulfate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

July 2003

Detailed Description:

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

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00070083

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
British Columbia Cancer Agency - Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Fraser Valley Cancer Centre at British Columbia Cancer Agency
Surrey, British Columbia, Canada, V3V 1Z2

Sponsors and Collaborators

British Columbia Cancer Agency

National Cancer Institute (NCI)

Investigators

Study Chair:

Richard J. Klasa, MD

British Columbia Cancer Agency

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000329985, BCCA-NCI-5818, NCI-5818
Study First Received:	October 3, 2003
Last Updated:	April 4, 2009
ClinicalTrials.gov Identifier:	NCT00070083 History of Changes
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:

Anti-Inflammatory Agents
Prednisone
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Cyclophosphamide
Antibiotics, Antineoplastic
Hormones
Lymphoma, B-Cell
Therapeutic Uses
Lymphoma
Alkylating Agents
Lymphoma, Large B-Cell, Diffuse

Immunoproliferative Disorders
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Rituximab
Mitosis Modulators
Vincristine
Antimitotic Agents
Glucocorticoids
Immunosuppressive Agents
Doxorubicin
Pharmacologic Actions
Lymphatic Diseases
Neoplasms
Tubulin Modulators

ClinicalTrials.gov processed this record on November 27, 2009