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

Leukemia Clinical Trial

Official title:

Phase I Clinical Evaluation of Bryostatin 1 in Combination With 2-CdA in Patients With Relapsed CLL

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003174
• Other study ID #: CDR0000065984
• Secondary ID: P30CA022453WSU-C
• Status: Completed
• Phase: Phase 1
• First received: November 1, 1999
• Last updated: April 22, 2014
• Start date: May 1998
• Est. completion date: November 2005

Study information

• Verified date: April 2014
• Source: Barbara Ann Karmanos Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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: 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: November 2005
• Est. primary completion date: November 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• bryostatin 1

• cladribine

Locations

Country	Name	City	State
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Barbara Ann Karmanos Cancer Institute	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Ahmad I, Al-Katib AM, Beck FW, Mohammad RM. Sequential treatment of a resistant chronic lymphocytic leukemia patient with bryostatin 1 followed by 2-chlorodeoxyadenosine: case report. Clin Cancer Res. 2000 Apr;6(4):1328-32. — View Citation