Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Related Publications
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	NCI	WSU-C-1388 NCI-T97-0016, NCT00003174, T97-0016

Objectives

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

Entry 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

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

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/mm³
• Platelet count at least 50,000/mm³

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

Expected Enrollment

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

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.

Ahmad I, Al-Katib AM, Beck FW, et al.: Sequential treatment of a resistant chronic lymphocytic leukemia patient with bryostatin 1 followed by 2-chlorodeoxyadenosine: case report. Clin Cancer Res 6 (4): 1328-32, 2000.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Barbara Ann Karmanos Cancer Institute

Ayad Al-Katib, MD, FACP, Protocol chair		Ph: 313-745-8853

Registry Information
Official Title		Phase I Clinical Evaluation of Bryostatin 1 in Combination with 2-CdA in Patients with Relapsed CLL
Trial Start Date		1998-05-21
Registered in ClinicalTrials.gov		NCT00003174
Date Submitted to PDQ		1997-12-31
Information Last Verified		2006-04-13
NCI Grant/Contract Number		CA22453

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