Combination Chemotherapy in Treating Patients With Chronic Lymphocytic Leukemia or Lymphocytic Lymphoma

This study has been completed.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University Health Network, Toronto Identifier:
First received: September 6, 2002
Last updated: July 22, 2015
Last verified: July 2015

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase I/II trial to study the effectiveness of combining UCN-01 with fludarabine in treating patients who have relapsed or refractory chronic lymphocytic leukemia or lymphocytic lymphoma.

Condition Intervention Phase
Drug: 7-hydroxystaurosporine
Drug: fludarabine phosphate
Phase 1
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Phase I/II Study Of UCN-01 In Combination With Fludarabine In Patients With Relapsed Or Refractory Chronic Lymphocytic Leukemia Or Small Lymphocytic Lymphoma

Resource links provided by NLM:

Further study details as provided by University Health Network, Toronto:

Study Start Date: June 2002
Primary Completion Date: December 2003 (Final data collection date for primary outcome measure)
Detailed Description:


  • Determine the overall response rate in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma treated with UCN-01 and fludarabine.
  • Assess the molecular changes in CLL cells in peripheral blood in patients treated with this regimen.
  • Determine the progression-free and overall survival of patients treated with this regimen.
  • Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter, dose-escalation study of UCN-01.

Patients receive UCN-01 IV over 3 hours on day 1 and fludarabine IV over 30-60 minutes on days 1-5. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of UCN-01 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 18-46 additional patients receive UCN-01 and fludarabine as above at the recommended phase II dose.

PROJECTED ACCRUAL: A total of 12 patients will be accrued for the phase I portion of this study within 6 months. A total of 18-46 patients will be accrued for the phase II portion of this study within 9-23 months.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • Histologically or cytologically confirmed chronic lymphocytic leukemia (CLL) or B-cell small lymphocytic lymphoma (SLL)

    • CLL is defined as:

      • Persistent lymphocytosis greater than 5,000/mm^3
      • CD19/CD5/CD23 positive
      • Kappa or lambda light chain restriction
  • Refractory to or disease progression after 1 or 2 prior treatment regimens

    • Retreatment with oral chlorambucil is allowed and considered a second regimen

      • At least one of the chlorambucil treatments must be for 3 months or longer
    • At least 4 courses of cyclophosphamide, vincristine, and prednisone with or without doxorubicin allowed
    • Patients may have received prior fludarabine as first- or second-line therapy if there is evidence of at least partial response and time to progression after initial fludarabine therapy was at least 12 months
  • No CNS involvement by lymphoma



  • 18 and over

Performance status

  • ECOG 0-2 OR
  • Karnofsky 60-100%

Life expectancy

  • More than 3 months


  • See Disease Characteristics
  • Absolute neutrophil count at least 1,000/mm^3
  • Platelet count at least 100,000/mm^3
  • No autoimmune hemolytic anemia or thrombocytopenia secondary to CLL or SLL requiring ongoing therapy with prednisone or other immunosuppressive agents


  • Bilirubin normal
  • AST and ALT no greater than 2.5 times upper limit of normal


  • Creatinine normal OR
  • Creatinine clearance at least 60 mL/min


  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia


  • DLCO greater than 60% predicted
  • FEV_1 greater than 70% predicted
  • No significant underlying pulmonary disease


  • No other malignancy within the past 5 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix
  • No insulin-dependent diabetes mellitus
  • No other uncontrolled concurrent illness
  • No ongoing or active infection
  • No pre-existing peripheral neuropathy grade 2 or greater
  • No psychiatric illness or social situation that would preclude study compliance
  • No prior allergic reactions to compounds of similar chemical or biological composition to UCN-01 or other agents in this study
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception


Biologic therapy

  • Not specified


  • See Disease Characteristics
  • At least 4 weeks since prior chemotherapy and recovered

Endocrine therapy

  • See Hematopoietic


  • No prior mediastinal radiation
  • At least 4 weeks since prior radiotherapy and recovered


  • Not specified


  • No other concurrent investigational agents
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  Contacts and Locations
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Please refer to this study by its identifier: NCT00045513

Canada, Ontario
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8N 3Z5
London Health Sciences Centre
London, Ontario, Canada, N6A 465
Princess Margaret Hospital at University Health Network
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
University Health Network, Toronto
National Cancer Institute (NCI)
Study Chair: Michael R. Crump, MD, FRCPC Princess Margaret Hospital, Canada
  More Information

Additional Information:
No publications provided

Responsible Party: University Health Network, Toronto Identifier: NCT00045513     History of Changes
Other Study ID Numbers: PMH-PHL-006, CDR0000256600, NCI-5538
Study First Received: September 6, 2002
Last Updated: July 22, 2015
Health Authority: United States: Federal Government

Keywords provided by University Health Network, Toronto:
refractory chronic lymphocytic leukemia
recurrent small lymphocytic lymphoma

Additional relevant MeSH terms:
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Fludarabine phosphate
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses processed this record on November 27, 2015