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

Sponsor

Barbara Ann Karmanos Cancer Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00003174

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

90.1

Duration (Months)

26.7

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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: 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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: bryostatin 1 Drug: cladribine	Phase 1

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 1998

Actual Primary Completion Date :

Nov 1, 2005

Actual Study Completion Date :

Nov 1, 2005

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48202-1379
2	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan	United States	48202
3	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236