A Phase I Study Of G3139 Antisense Oligonucleotide (Oblimersen) In Combination With CHOP And Rituximab In Untreated Advanced Stage Diffuse Large B Cell Lymphoma
19 Years
N/A
Both
Lymphoma
Trial Information
A Phase I Study Of G3139 Antisense Oligonucleotide (Oblimersen) In Combination With CHOP And Rituximab In Untreated Advanced Stage Diffuse Large B Cell Lymphoma
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Richard J. Klasa, MD
Investigator Role:
Study Chair
Investigator Affiliation:
British Columbia Cancer Agency
Authority:
United States: Federal Government
Study ID:
CDR0000329985
NCT ID:
NCT00070083
Start Date:
July 2003
Completion Date:
Related Keywords:
- Lymphoma
- 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
- Lymphoma
- Lymphoma, B-Cell
- Lymphoma, Large B-Cell, Diffuse
Name | Location |
|---|---|
| Stanford Cancer Center at Stanford University Medical Center | Stanford, California 94305 |
