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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00019838
First received: July 11, 2001
Last updated: August 22, 2012
Last verified: February 2005
  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 1

Study Type: Interventional
Study Design: Primary Purpose: 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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Investigators
Study Chair: Wyndham H. Wilson, MD, PhD National Cancer Institute (NCI)
  More Information

Additional Information:
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.

ClinicalTrials.gov Identifier: NCT00019838     History of Changes
Obsolete Identifiers: NCT00001822
Other Study ID Numbers: CDR0000067252, NCI-99-C-0127, NCI-T99-0022
Study First Received: July 11, 2001
Last Updated: August 22, 2012
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
Waldenström 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:
Lymphoma
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Fludarabine
Fludarabine phosphate
7-hydroxystaurosporine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014