Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	19 and over	NCI	BCCA-NCI-5818 NCI-5818, NCT00070083, 5818

Objectives

Primary

1. 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.
2. Determine the maximum tolerated dose of oblimersen administered with this regimen in these patients.

Secondary

1. Determine the remission rate and failure-free, progression-free, and overall survival of patients treated with this regimen.

Entry 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/mm³



• No history of other lymphoproliferative disorder



• No history of indolent lymphoma



• No T-cell lymphoma



• No CNS involvement



• No post-transplantation lymphoproliferative disorder

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

Patient Characteristics:

Age

• 19 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm³ (unless due to bone marrow involvement with lymphoma)
• Platelet count at least 100,000/mm³ (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

Expected Enrollment

A total of 19-28 patients will be accrued for this study within 5-10 months.

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.

Trial Contact Information

Trial Lead Organizations

British Columbia Cancer Agency - Vancouver Cancer Centre

Richard Klasa, MD, Protocol chair		Ph: 604-877-6000 ext. 2730; 800-663-3333 Email: rklasa@bccancer.bc.ca

Registry Information
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
Trial Start Date		2003-07-30
Registered in ClinicalTrials.gov		NCT00070083
Date Submitted to PDQ		2003-08-12
Information Last Verified		2005-06-23
NCI Grant/Contract Number		CN85188

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