We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00045513
First Posted: January 27, 2003
Last Update Posted: July 23, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University Health Network, Toronto
  Purpose

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
Leukemia Lymphoma 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:

OBJECTIVES:

  • 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.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-2 OR
  • Karnofsky 60-100%

Life expectancy

  • More than 3 months

Hematopoietic

  • 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

Hepatic

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

Renal

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

Cardiovascular

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

Pulmonary

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

Other

  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

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

Endocrine therapy

  • See Hematopoietic

Radiotherapy

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

Surgery

  • Not specified

Other

  • No other concurrent investigational agents
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00045513


Locations
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)
Investigators
Study Chair: Michael R. Crump, MD, FRCPC Princess Margaret Hospital, Canada
  More Information

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT00045513     History of Changes
Other Study ID Numbers: PMH-PHL-006
CDR0000256600 ( Registry Identifier: PDQ (Physician Data Query) )
NCI-5538
First Submitted: September 6, 2002
First Posted: January 27, 2003
Last Update Posted: July 23, 2015
Last Verified: July 2015

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

Additional relevant MeSH terms:
Lymphoma
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Fludarabine
Fludarabine phosphate
7-hydroxystaurosporine
Staurosporine
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors