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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00045513
• Other study ID #: PMH-PHL-006
• Secondary ID: CDR0000256600NCI
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 6, 2002
• Last updated: July 22, 2015
• Start date: June 2002

Study information

• Verified date: July 2015
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. primary completion date: December 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma

Intervention

Drug:
• 7-hydroxystaurosporine

• fludarabine phosphate

Locations

Country	Name	City	State
Canada	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	Princess Margaret Hospital at University Health Network	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
University Health Network, Toronto	National Cancer Institute (NCI)

Country where clinical trial is conducted

Canada,