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Phase I Study of Bryostatin 1 (NSC 339555) and Fludarabine in Patients With Chronic Lymphocytic Leukemia and Indolent Non-Hodgkin's Lymphoma


Phase 1
18 Years
N/A
Not Enrolling
Both
Leukemia, Lymphoma

Thank you

Trial Information

Phase I Study of Bryostatin 1 (NSC 339555) and Fludarabine in Patients With Chronic Lymphocytic Leukemia and Indolent Non-Hodgkin's Lymphoma


OBJECTIVES:

- Determine the toxic effects and maximum tolerated dose of bryostatin 1 and fludarabine
in patients with symptomatic or advanced chronic lymphocytic leukemia or relapsed
indolent non-Hodgkin's lymphoma.

- Monitor apoptosis, differentiation, and protein kinase C activity in leukemic
lymphocytes exposed in vivo to bryostatin 1 and fludarabine.

- Observe the antitumor activity of this combination therapy in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are assigned to one of two
treatment groups.

- Group I: Patients receive bryostatin 1 IV over 24 hours followed by fludarabine IV over
30 minutes daily on days 1-5.

- Group II: Patients receive fludarabine IV over 30 minutes daily on days 1-5 followed by
bryostatin 1 IV over 24 hours.

In both groups, courses repeat every 4 weeks for patients with stable or responding disease.

Cohorts of 3-6 patients receive escalating doses of fludarabine and bryostatin 1 until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 6 patients experience dose-limiting toxicity. Once the MTD for fludarabine is
determined, the dose of bryostatin 1 is escalated.

PROJECTED ACCRUAL: Approximately 30-60 patients will be accrued for this study within 3
years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed chronic lymphocytic leukemia

- Stage I (symptomatic or with bulky lymphadenopathy)

- Stage II, III, or IV

- Prior chemotherapy allowed, including fludarabine or other purine nucleoside
analog therapy OR

- Histologically confirmed indolent non-Hodgkin's lymphoma

- Progressive or relapsed following chemotherapy

- Includes the following histologies:

- B-cell chronic lymphocytic leukemia/prolymphocytic leukemia/lymphomas

- Lymphoplasmacytoid lymphoma (Waldenstrom's)/immunocytoma

- Mantle cell lymphoma

- Follicular lymphoma

- Small cell

- Mixed small and large cell

- Diffuse (predominately small cell type)

- Marginal zone B-cell lymphoma

- Extranodal (MALT-type with or without monocytoid B-cells)

- Provisional subtype: nodal (with or without monocytoid B-cells)

- Provisional entity: splenic marginal zone lymphoma (with or without villous
lymphocytes)

- Hairy cell leukemia

- Peripheral T-cell and NK-cell neoplasms

- T-cell chronic lymphocytic leukemia/polylymphocytic leukemia

- Large granular lymphocyte leukemia

- T-cell type

- NK-cell type

- Mycosis fungoides/Sezary's syndrome (cutaneous T-cell lymphoma)

- No CNS disease

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- Zubrod 0-2

Life expectancy:

- Not specified

Hematopoietic:

- Granulocyte count at least 1,000/mm3

- Platelet count at least 75,000/mm3

- Hemoglobin at least 8 g/dL

- Coombs negative

Hepatic:

- AST/ALT no greater than 2.5 times upper limit of normal

- Bilirubin no greater than 2 mg/mL

Renal:

- Creatinine clearance at least 40 mL/min

Other:

- No concurrent neurologic condition

- No other concurrent medical condition that would preclude study

- Not pregnant or nursing

- Fertile patients must use effective contraception during and for 3 months after study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- No concurrent systemic immunoglobulin therapy

- No prior bone marrow or peripheral stem cell transplantation

Chemotherapy:

- See Disease Characteristics

- At least 3 weeks since prior systemic chemotherapy

Endocrine therapy:

- No concurrent systemic glucocorticoid therapy

Radiotherapy:

- Not specified

Surgery:

- Not specified

Other:

- No other concurrent anticancer therapy

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Steven Grant, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Massey Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000066433

NCT ID:

NCT00005580

Start Date:

September 1998

Completion Date:

August 2006

Related Keywords:

  • Leukemia
  • Lymphoma
  • recurrent cutaneous T-cell non-Hodgkin lymphoma
  • Waldenstrom macroglobulinemia
  • stage I chronic lymphocytic leukemia
  • stage II chronic lymphocytic leukemia
  • stage III chronic lymphocytic leukemia
  • stage IV chronic lymphocytic leukemia
  • refractory chronic lymphocytic leukemia
  • T-cell large granular lymphocyte leukemia
  • B-cell chronic lymphocytic leukemia
  • refractory hairy cell leukemia
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • recurrent adult T-cell leukemia/lymphoma
  • prolymphocytic leukemia
  • recurrent mantle cell lymphoma
  • recurrent mycosis fungoides/Sezary syndrome
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone lymphoma
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Lymphoma
  • Lymphoma, Non-Hodgkin

Name

Location
Fox Chase Cancer Center Philadelphia, Pennsylvania  19111
New York Presbyterian Hospital - Cornell Campus New York, New York  10021
Massey Cancer Center Richmond, Virginia  23298-0037