Bryostatin 1 Plus Cladribine in Treating Patients With Relapsed Chronic Lymphocytic Leukemia
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Purpose
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 | Intervention | Phase |
|---|---|---|
|
Leukemia |
Drug: bryostatin 1 Drug: cladribine |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | 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 1998 |
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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| United States, Michigan | |
| Barbara Ann Karmanos Cancer Institute | |
| Detroit, Michigan, United States, 48202-1379 | |
| Josephine Ford Cancer Center at Henry Ford Hospital | |
| Detroit, Michigan, United States, 48202 | |
| Van Elslander Cancer Center at St. John Hospital and Medical Center | |
| Grosse Pointe Woods, Michigan, United States, 48236 | |
| Study Chair: | Ayad M. Al-Katib, MD, FACP | Barbara Ann Karmanos Cancer Institute |
More Information
Additional Information:
Publications:
| ClinicalTrials.gov Identifier: | NCT00003174 History of Changes |
| Other Study ID Numbers: | CDR0000065984, WSU-C-1388, NCI-T97-0016 |
| Study First Received: | November 1, 1999 |
| Last Updated: | July 23, 2008 |
| Health Authority: | United States: Federal Government |
Keywords provided by National Cancer Institute (NCI):
|
stage I chronic lymphocytic leukemia stage II chronic lymphocytic leukemia stage III chronic lymphocytic leukemia stage IV chronic lymphocytic leukemia refractory chronic lymphocytic leukemia |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Neoplasms by Histologic Type Neoplasms Leukemia, B-Cell Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases |
Bryostatin 1 Cladribine Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Adjuvants, Immunologic Immunologic Factors Physiological Effects of Drugs Immunosuppressive Agents |
ClinicalTrials.gov processed this record on May 22, 2013