A Phase I Study Of G3139 Antisense Oligonucleotide (Oblimersen) In Combination With CHOP And Rituximab In Untreated Advanced Stage Diffuse Large B Cell Lymphoma
- 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
- 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
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
Primary Purpose: Treatment
Richard J. Klasa, MD
British Columbia Cancer Agency
United States: Federal Government
|Stanford Cancer Center at Stanford University Medical Center||Stanford, California 94305|