Clinical trial NCT00002908: Bryostatin 1 in Treating Patients With Relapsed Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia
Official title: PHASE II CLINICAL EVALUATION OF BRYOSTATIN 1 IN PATIENTS WITH RELAPSED NON-HODGKIN'S LYMPHOMA AND CLL
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Lymphoma
Keywords: refractory chronic lymphocytic leukemia
recurrent small lymphocytic lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
Lead sponsor: Barbara Ann Karmanos Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-07-19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
Study officials:
affiliation: Barbara Ann Karmanos Cancer Institute
name: Ayad M. Al-Katib, MD, FACP
role: STUDY_CHAIR
References: