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

Primary Purpose

Leukemia, Lymphoma

Status
Completed
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
7-hydroxystaurosporine
fludarabine phosphate
Sponsored by
University Health Network, Toronto
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring refractory chronic lymphocytic leukemia, recurrent small lymphocytic lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • McMaster Children's Hospital at Hamilton Health Sciences
  • London Health Sciences Centre
  • Princess Margaret Hospital at University Health Network

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
September 6, 2002
Last Updated
July 22, 2015
Sponsor
University Health Network, Toronto
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00045513
Brief Title
Combination Chemotherapy in Treating Patients With Chronic Lymphocytic Leukemia or Lymphocytic Lymphoma
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2015
Overall Recruitment Status
Completed
Study Start Date
June 2002 (undefined)
Primary Completion Date
December 2003 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma
Keywords
refractory chronic lymphocytic leukemia, recurrent small lymphocytic lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
7-hydroxystaurosporine
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael R. Crump, MD, FRCPC
Organizational Affiliation
Princess Margaret Hospital, Canada
Official's Role
Study Chair
Facility Information:
Facility Name
McMaster Children's Hospital at Hamilton Health Sciences
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 3Z5
Country
Canada
Facility Name
London Health Sciences Centre
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 465
Country
Canada
Facility Name
Princess Margaret Hospital at University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada

12. IPD Sharing Statement

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

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