RATIONALE: Drugs used in chemotherapy such as vincristine use different ways to stop cancer cells from dividing so they stop growing or die. Bryostatin 1 may help vincristine kill more cancer cells by making the cells more sensitive to the drug.

PURPOSE: Phase II trial to study the effectiveness of combining bryostatin 1 with vincristine in treating patients who have progressive or relapsed non-Hodgkin's lymphoma after autologous bone marrow transplantation or autologous stem cell transplantation.

Condition	Treatment or Intervention	Phase
adult non-Hodgkin's lymphoma	Drug: bryostatin 1  Drug: vincristine  Procedure: chemosensitization/potentiation  Procedure: chemotherapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the response rate of patients with low- or intermediate-grade non-Hodgkin's lymphoma who have progressed or relapsed after autologous bone marrow or stem cell transplantation treated with bryostatin 1 and vincristine.
• Determine whether blunting of apoptotic response using annexin V staining of peripheral blood CD5+ and CD19+ lymphocytes by flow cytometry is predictive of outcome (i.e., lack of clinical response) in patients treated with this regimen.
• Determine the incidence of grade 3 or greater myelotoxicity in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive bryostatin 1 IV over 24 hours and vincristine IV on days 1 and 15. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients without disease progression after 6 courses may continue therapy with bryostatin 1 IV and vincristine IV on days 1 and 22. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 16-28 patients will be accrued for this study within 18-24 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed non-Hodgkin's lymphoma (NHL)
• Relapsed or progressive disease after autologous bone marrow or peripheral blood stem cell transplantation
• Low- or intermediate-grade NHL of any of the following REAL classification subtypes:
• B-cell small lymphocytic
• Marginal zone/MALT
• Mantle cell
• Plasmacytoid
• Lymphoplasmacytoid
• Follicular grade I, II, or III
• Diffuse small cell
• Large B-cell
• At least 1 unidimensionally measurable lesion that is at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
• Must have received prior autologous bone marrow or peripheral blood stem cell transplantation
• No prior allogeneic transplantation
• No known brain metastases or leptomeningeal involvement NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 8-10 weeks

Hematopoietic

• Absolute neutrophil count at least 1,250/mm^3
• Platelet count at least 50,000/mm^3
• Hemoglobin at least 8.5 g/dL

Hepatic

• Bilirubin no greater than 2.0 mg/dL
• AST/ALT no greater than 3 times normal

Renal

• Creatinine no greater than 2.0 mg/dL

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
• HIV negative
• No clinically apparent grade 2 or greater neuropathy
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY: Biologic therapy

• See Disease Characteristics

Chemotherapy

• Prior vincristine allowed

Endocrine therapy

• No concurrent steroids

Radiotherapy

• At least 4 weeks since prior large-field radiotherapy

Surgery

• Not specified

Other

• At least 4 weeks since prior anticancer therapy and recovered
• No other concurrent anticancer therapy

Michigan
      Josephine Ford Cancer Center at Henry Ford Health System, Detroit,  Michigan,  48202,  United States; Recruiting
New Jersey
      CCOP - Northern New Jersey, Hackensack,  New Jersey,  07601,  United States; Recruiting
Ohio
      Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University, Cleveland,  Ohio,  44106-5065,  United States; Recruiting
Oregon
      Cancer Institute at Oregon Health and Science University, Portland,  Oregon,  97239-3098,  United States; Recruiting
Pennsylvania
      Abramson Cancer Center at the University of Pennsylvania, Philadelphia,  Pennsylvania,  19104-4283,  United States; Recruiting
      Hillman Cancer Center at University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15232,  United States; Recruiting

Study chairs or principal investigators

Scot C. Remick, MD,  Study Chair,  Ireland Cancer Center   

Study ID Numbers:  CDR0000288817; CWRU-ICC-2402; NCI-5922; NCT00058305
Record last reviewed:  May 2004
Last Updated:  February 4, 2005
Record first received:  April 7, 2003
ClinicalTrials.gov Identifier:  NCT00058305
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08