UCN-01 and Fludarabine in Treating Patients With Recurrent or Refractory Lymphoma or Leukemia - Full Text View

Sponsor:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00019838

Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining UCN-01 with chemotherapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of fludarabine when given with UCN-01 in treating patients with recurrent or refractory low-grade lymphoma or leukemia.

Condition	Intervention	Phase
Leukemia Lymphoma	Drug: 7-hydroxystaurosporine Drug: fludarabine phosphate	Phase I

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Phase I and Pharmacokinetic Study of UCN-01 and Fludarabine in Relapsed or Refractory Low-Grade Lymphoid Malignancies

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma

Drug Information available for: Fludarabine Fludarabine monophosphate UCN 01

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

July 1999

Detailed Description:

OBJECTIVES:

Determine the maximum tolerated dose and toxic effects of fludarabine when administered with UCN-01 in patients with recurrent or refractory low-grade or indolent lymphoid malignancies.
Determine, preliminarily, the activity of this treatment regimen in these patients.
Assess the pharmacokinetics of this treatment regimen in these patients.

OUTLINE: This is a dose-escalation study of fludarabine.

Patients receive UCN-01 IV over 72 hours on days 1-3 alone during course 1 and over 36 hours on days 1-2 during courses 2-7. Patients also receive fludarabine IV over 30 minutes beginning on day 1 and continuing for up to 5 days during courses 2-7. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of fludarabine 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 every 2 months for 6 months, every 3 months for 1 year, and then every 6 months thereafter.

PROJECTED ACCRUAL: Approximately 20 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

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed recurrent or refractory low-grade or indolent lymphoid malignancies requiring systemic therapy, including the following:
- Grade I or II follicular small cleaved cell lymphoma
- Small lymphocytic lymphoma/leukemia subtypes (chronic lymphocytic leukemia)
- Mantle cell lymphoma
- Waldenstrom's macroglobulinemia
- Lymphoplasmacytoid
- Marginal zone (nodal, extranodal, or splenic subtypes)
- Hairy cell leukemia
Transformed indolent subtypes allowed provided 1 of the following criteria are met:
- Previously treated with a doxorubicin-containing regimen
- No rapidly progressing disease that threatens vital functions
Measurable disease
No active leptomeningeal or parenchymal CNS lymphoma NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

Karnofsky 60-100%

Life expectancy:

Not specified

Hematopoietic:

Absolute neutrophil count at least 1,000/mm^3
Platelet count at least 50,000/mm^3
No active Coomb's-positive hemolytic anemia

Hepatic:

Total bilirubin less than 2.0 mg/dL (unless elevation is due to Gilbert's disease and direct bilirubin is normal)

Renal:

Creatinine less than 1.5 mg/dL OR
Creatinine clearance greater than 60 mL/min

Cardiovascular:

No angina
No congestive heart failure
No myocardial infarction within the past 6 months

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
HIV negative
No insulin-dependent diabetes mellitus

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

See Disease Characteristics
More than 3 weeks since prior systemic chemotherapy and recovered

Endocrine therapy:

More than 3 weeks since prior systemic steroid therapy and recovered

Radiotherapy:

Not specified

Surgery:

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00019838

Locations

United States, Maryland
NCI - Center for Cancer Research
Bethesda, Maryland, United States, 20892
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Study Chair:

Wyndham H. Wilson, MD, PhD

National Cancer Institute (NCI)

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Wilson WH, Gutierrez M, Stetler-Stevenson M, et al.: Phase I trial of 7-hydroxystaurosporine (UCN-01) and fludararbine phosphate (FAMP); in vivo evidence of UCN-01 induced apoptosis in CLL. [Abstract] Blood 96 (11 Pt 1): A-3268, 756a, 2000.

Study ID Numbers:	CDR0000067252, NCI-99-C-0127, NCI-T99-0022
Study First Received:	July 11, 2001
Last Updated:	December 13, 2008
ClinicalTrials.gov Identifier:	NCT00019838 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

Waldenstrom macroglobulinemia
refractory chronic lymphocytic leukemia
refractory hairy cell leukemia
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent mantle cell lymphoma

recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Vidarabine
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Protein Kinase Inhibitors
Leukemia
Therapeutic Uses
Staurosporine
Lymphoma

Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Enzyme Inhibitors
7-hydroxystaurosporine
Fludarabine monophosphate
Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Lymphatic Diseases
Neoplasms
Fludarabine
Lymphoproliferative Disorders

ClinicalTrials.gov processed this record on November 27, 2009