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Combination Chemotherapy in Treating Patients With Chronic Lymphocytic Leukemia or Lymphocytic Lymphoma
This study is ongoing, but not recruiting participants.
Study NCT00045513   Information provided by National Cancer Institute (NCI)
First Received: September 6, 2002   Last Updated: July 23, 2008   History of Changes

September 6, 2002
July 23, 2008
June 2002
 
 
 
Complete list of historical versions of study NCT00045513 on ClinicalTrials.gov Archive Site
 
 
 
Combination Chemotherapy in Treating Patients With Chronic Lymphocytic Leukemia or Lymphocytic Lymphoma
Phase I/II Study Of UCN-01 In Combination With Fludarabine In Patients With Relapsed Or Refractory Chronic Lymphocytic Leukemia Or Small Lymphocytic Lymphoma

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.

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.

Phase I, Phase II
Interventional
Treatment
  • Leukemia
  • Lymphoma
  • Drug: 7-hydroxystaurosporine
  • Drug: fludarabine phosphate
 
 

*   Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
 
Active, not recruiting
 
 
 

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT00045513
 
CDR0000256600, PMH-PHL-006, NCI-5538
Princess Margaret Hospital, Canada
National Cancer Institute (NCI)
Study Chair: Michael R. Crump, MD, FRCPC Princess Margaret Hospital, Canada
National Cancer Institute (NCI)
March 2004

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP