Purpose:
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die. Combining more than one drug may kill more tumor cells.
PURPOSE: Phase I/II trial to study the effectiveness of bryostatin 1 in treating patients
who have relapsed non-Hodgkin's lymphoma or chronic lymphocytic leukemia.
Study summary:
OBJECTIVES: I. Assess the efficacy of bryostatin 1 administered as a 72-hour infusion in
patients with relapsed non-Hodgkin's lymphoma and chronic lymphocytic leukemia. II. Gain
information regarding the toxicity and tolerability of escalated vincristine doses given
after each bryostatin 1 infusion in cohorts of patients who fail to respond to bryostatin
alone. III. Determine the qualitative and quantitative toxic effects of bryostatin 1 in
these patients. IV. Determine the duration of response and survival following treatment with
bryostatin 1.
OUTLINE: All patients receive bryostatin 1 by 72-hour continuous infusion every 2 weeks
until disease progression or until 2 courses beyond documentation of complete remission.
Response is assessed after every 4 courses. Patients with disease progression who continue
to meet the eligibility criteria receive vincristine within 2 hours after completion of each
bryostatin 1 infusion. Groups of 3-6 patients receive escalated doses of vincristine until
the maximum tolerated dose with bryostatin 1 is determined. Courses repeat every 2 weeks, as
above; no individual dose escalation is allowed. No concurrent steroids are permitted.
Patients are followed for survival.
PROJECTED ACCRUAL: A total of 25 evaluable patients with low-grade NHL or CLL will be
entered over approximately 20 months if there are 2-4 responses in the first 15 patients. A
total of 20 evaluable patients with intermediate- or high-grade NHL will be entered over
approximately 2 years if there are 1 or 2 responses in the first 10 patients.
Criteria:
DISEASE CHARACTERISTICS: One of the following hematologic malignancies that has failed 1
or 2 prior front-line chemotherapy regimens and is ineligible for treatment of higher
potential efficacy: Histologically confirmed chronic lymphocytic leukemia (CLL)
Intermediate- or high-risk (RAI stage I-IV) disease Evidence of active disease required by
at least one of the following for intermediate-risk CLL: One of the following B symptoms:
Weight loss of 10% or more in previous 6 months Extreme fatigue Fever over 100 F without
evidence of infection Night sweats Massive (more than 6 cm below left costal margin) or
progressive splenomegaly Massive (more than 10 cm in longest diameter) or progressive
lymphadenopathy Progressive lymphocytosis with more than 50% increase over 2-month period
or anticipated doubling time of less than 12 months Progressive bone marrow failure as
manifested by development or worsening of anemia and/or thrombocytopenia Autoimmune anemia
and/or thrombocytopenia poorly responsive to corticosteroids Biopsy proven low-,
intermediate-, or high-grade non-Hodgkin's lymphoma Transformed lymphoma allowed
Measurable disease required Re-treatment on this study allowed if disease relapsed after a
complete remission
PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Zubrod 0-2 Life expectancy:
At least 12 weeks Hematopoietic: ANC at least 1,500/mm3 (at least 1,000/mm3 in CLL
patients with at least 30% marrow involvement) Platelets at least 100,000/mm3 (at least
50,000/mm3 in CLL patients with at least 30% marrow involvement) Hepatic: Bilirubin less
than 1.5 mg/dL Transaminases less than 2.5 times normal Renal: Creatinine no greater than
1.5 mg/dL OR Creatinine clearance at least 60 mL/min Cardiovascular: No history of
impaired cardiac status, e.g.: Severe coronary artery disease Cardiomyopathy Uncontrolled
congestive heart failure Arrhythmia Other: No known AIDS or HIV infection No second
malignancy within 5 years except: Adequately treated nonmelanomatous skin cancer In situ
cervical cancer Not pregnant or nursing Effective contraception required of fertile
patients during and for 2 months after study
PRIOR CONCURRENT THERAPY: No concurrent therapy Biologic therapy: Not specified
Chemotherapy: See Disease Characteristics At least 4 weeks since chemotherapy (8 weeks
since nitrosoureas or mitomycin) and recovered Endocrine therapy: Not specified
Radiotherapy: At least 4 weeks since radiotherapy and recovered Surgery: Not specified
Other: No prior bone marrow transplant