A Phase II Study Of Epothilone B Analog BMS-247550 (NSC 710428) In Patients With Relapsed Aggressive Non-Hodgkin's Lymphomas
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed aggressive non-Hodgkin's lymphoma of 1 of the following
cellular types:
- Grade III follicular center
- Diffuse large B-cell
- Mantle cell
- Primary mediastinal B-cell
- Burkitt's
- High-grade B-cell (Burkitt-like)
- Anaplastic large cell of 1 of the following subtypes:
- CD30-positive
- T-cell
- Null cell
- Hodgkin's-like
- Relapsed or refractory disease after prior standard chemotherapy, meeting criteria
for 1 of the following cohorts:
- Cohort 1 (relapsed but chemosensitive): Prior complete response (CR) or partial
response (PR) lasting at least 4 weeks after the most recent prior therapy
- Cohort 2 (refractory): Stable disease or less than a PR after the most recent
prior therapy
- No progressive disease after the most recent prior therapy
- Measurable disease
- At least 1 bidimensionally measurable lesion at least 10 mm by conventional
techniques or clinical exam
- Ineligible for or unwilling to undergo hematopoietic stem cell transplantation
- Patients requiring debulking prior to transplant allowed
- No known CNS involvement by lymphoma
- Prior CNS disease that has been successfully treated in patients with relapsed
disease exclusively outside of the CNS may be allowed by the principal
investigator
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2
Life expectancy
- More than 3 months
Hematopoietic
- WBC at least 3,000/mm^3
- Absolute neutrophil count at least 1,200/mm^3
- Platelet count at least 100,000/mm^3
Hepatic
- Bilirubin no greater than 1.5 mg/dL
- AST/ALT no greater than 2.5 times upper limit of normal
Renal
- Creatinine no greater than 1.5 mg/dL OR
- Creatinine clearance at least 60 mL/min
Cardiovascular
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No prior allergic reaction or hypersensitivity to compounds containing Cremophor EL
or agents of similar chemical or biological composition to BMS-247550
- No peripheral neuropathy grade 2 or greater
- No other currently active malignancy except nonmelanoma skin cancer or carcinoma in
situ of the cervix (previously treated malignancy allowed if considered to be at less
than 30% risk of relapse)
- No ongoing or active infection
- No psychiatric illness or social situation that would preclude study compliance
- No other concurrent uncontrolled illness
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No colony-stimulating factors (CSFs) within 24 hours of study chemotherapy
- No CSFs during first course of study therapy
- No concurrent filgrastim-SD/01
- No concurrent immunotherapy
Chemotherapy
- See Disease Characteristics
- At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas or
mitomycin)
- No other concurrent chemotherapy
Endocrine therapy
- No concurrent hormonal therapy
Radiotherapy
- At least 4 weeks since prior radiotherapy
- No concurrent therapeutic radiotherapy
Surgery
- At least 4 weeks since prior surgery
Other
- Recovered from prior therapy
- At least 7 days since prior cimetidine
- No concurrent cimetidine
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent investigational agents
- No other concurrent anticancer medications
- No concurrent unconventional therapies, food, or vitamin supplements containing
Hypericum perforatum