Bryostatin 1 Plus Cladribine in Treating Patients With Relapsed Chronic Lymphocytic Leukemia

Barbara Ann Karmanos Cancer Institute

Status and phase: Completed; Phase 1

Conditions: Leukemia

Treatments: Drug: cladribine; Drug: bryostatin 1

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00003174

WSU-C-1388

CDR0000065984

P30CA022453 (U.S. NIH Grant/Contract)

NCI-T97-0016

Details and patient eligibility

About

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: This phase I trial is studying the side effects and best dose of cladribine when given with bryostatin 1 in treating patients with relapsed chronic lymphocytic leukemia.

Full description

OBJECTIVES:

• Determine the maximum tolerated dose of cladribine when administered after bryostatin 1 in patients with relapsed chronic lymphocytic leukemia.
• Determine the qualitative and quantitative toxic effects of this regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study of cladribine.

Patients receive bryostatin 1 IV continuously on days 1-3 immediately followed by cladribine IV continuously on days 4-8. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients who achieve complete remission (CR) receive 2 additional courses past CR.

Cohorts of 3-6 patients receive escalating dose levels of cladribine 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.

Patients are followed at 3 weeks.

PROJECTED ACCRUAL: A minimum of 15 patients will be accrued for this study.

Enrollment: 80 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Diagnosis of relapsed chronic lymphocytic leukemia

  • Intermediate- or high-risk (stage I-IV) disease

• Intermediate-risk patients must have active disease, defined by at least 1 of the following criteria:

  • Presence of any 1 of the following disease-related B symptoms:

    • 10% or more loss of body weight within the past 6 months
    • Extreme fatigue
    • Fever greater than 100 degrees Fahrenheit without evidence of infection
    • Night sweats

  • Massive (greater than 6 cm below left costal margin) or progressive splenomegaly

  • Massive (greater than 10 cm in longest diameter) or progressive lymphadenopathy

  • Progressive lymphocytosis with an increase of more than 50% over a 2-month period or anticipated doubling time of less than 12 months

  • Progressive bone marrow failure as manifested by the development or worsening of anemia and/or thrombocytopenia

  • Autoimmune anemia and/or thrombocytopenia poorly responsive to corticosteroids

• Failed 1-2 prior front-line regimens

• Failed prior fludarabine

• Ineligible for any known treatment of higher potential efficacy

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Zubrod 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• See Disease Characteristics
• Absolute neutrophil count at least 1,000/mm^3
• Platelet count at least 50,000/mm^3

Hepatic:

• Bilirubin less than 1.5 mg/dL
• Transaminases less than 2.5 times normal

Renal:

• Creatinine less than 1.5 mg/dL OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No history of severe coronary artery disease, cardiomyopathy, uncontrolled congestive heart failure, or arrhythmias

Neurologic:

• No prior drug-related neurotoxicity
• No other neurologic disorder

Other:

• Not pregnant or nursing
• Fertile patients must use effective barrier or non-hormonal contraception during and for 2 months after study participation
• No HIV infection
• No AIDS

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior bone marrow transplantation

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy (8 weeks for mitomycin or nitrosoureas) and recovered

Endocrine therapy:

• See Disease Characteristics
• No concurrent steroids
• No concurrent hormonal contraceptives

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered

Surgery:

• Not specified

Other:

• No other concurrent therapy