Flavopiridol in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia or Lymphocytic Lymphoma

Recurrent Small Lymphocytic Lymphoma Clinical Trial

Official title:

A Dose-Escalation Study of Flavopiridol (NSC 649890) Administered as a 30 Minute Loading Dose Followed by a 4-Hour Infusion in Patients With Previously Treated B-Cell Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00058240
• Other study ID #: NCI-2012-01435
• Secondary ID: NCI-2012-01435CD
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: April 7, 2003
• Last updated: June 6, 2014
• Start date: April 2003
• Est. completion date: February 2009

Study information

• Verified date: November 2012
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This phase I/II trial studies the side effects and best dose of flavopiridol in treating patients with previously treated chronic lymphocytic leukemia or lymphocytic lymphoma. Drugs used in chemotherapy such as flavopiridol work in different ways to stop cancer cells from dividing so they stop growing or die.

Description:

PRIMARY OBJECTIVES:

I. To determine the toxicity profile, dose-limiting toxicity, and maximum tolerated dose of flavopiridol administered as a 30 minute loading dose followed by a 4-hour infusion once weekly for 4 consecutive weeks every 6 weeks.

II. To determine the safety and feasibility of performing dose escalation to 80 mg/m2 (30 mg/m2 30-minute IV bolus followed by 50 mg/m2 4-hour IV infusion) beginning dose 2 in patients who do not experience severe tumor lysis requiring hemodialysis during dose 1.

III. To determine the pharmacokinetics and cellular pharmacodynamics of flavopiridol administered in this schedule.

SECONDARY OBJECTIVES:

I. To determine the complete response (CR) and overall response rate (CR + PR) of flavopiridol in patients with previously-treated CLL administered as a 30 minute loading dose followed by a 4 hour infusion once weekly for 4 consecutive weeks every 6 weeks.

OUTLINE: This is a dose-escalation study.

Patients receive a loading dose of flavopiridol IV over 30 minutes followed by a 4-hour infusion on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. After the MTD is determined, 12 additional patients are accrued and treated as above at the recommended phase II dose.

After completion of study treatment, patients are followed at 2 months and then every 3 months for 2 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: February 2009
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of B-cell chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma, including Waldenstrom's macroglobulinemia, as indicated by the following:

• Massive or progressive splenomegaly and/or lymphadenopathy

• Anemia (hemoglobin less than 11 g/dL) or thrombocytopenia (platelet count less than 100,000/mm^3)

• Weight loss of more than 10% within the past 6 months

• Grade 2 or 3 fatigue

• Fevers greater than 100.5º C or night sweats for more than 2 weeks with no evidence of infection

• Progressive lymphocytosis with an increase of more than 50% over a 2-month period or anticipated doubling time of less than 6 months

• Received at least 1 prior therapy for CLL

• Performance status - ECOG 0-2

• See Disease Characteristics

• WBC less than 200,000/mm^3

• Bilirubin no greater than 1.5 times normal (unless due to Gilbert's disease or any of the conditions stated below)*

• AST no greater than 2 times normal*

• Creatinine no greater than 2.0 mg/dL

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No other malignancy that would limit survival to less than 2 years

• No history of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis) unless inactive for more than 2 years

• No psychiatric condition that would preclude compliance with treatment or giving informed consent

• No other concurrent chemotherapy

• No concurrent chronic corticosteroids

• No concurrent hormonal therapy except steroids for new adrenal failure or hormonal agents for nondisease-related conditions (e.g., insulin for diabetes)

• No concurrent dexamethasone or other corticosteroid-based antiemetics

• No concurrent radiotherapy

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• B-cell Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Recurrent Small Lymphocytic Lymphoma
• Refractory Chronic Lymphocytic Leukemia
• Waldenstrom Macroglobulinemia
• Waldenström Macroglobulinemia

Intervention

Drug:
• alvocidib
Given IV

Locations

Country	Name	City	State
United States	Ohio State University Medical Center	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of flavopiridol determined by dose-limiting toxicities graded assessed utilizing the NCI Common Toxicity Criteria 2.0		6 weeks	Yes
Secondary	Overall response rate (CR + PR) of flavopiridol in patients evaluated utilizing the Revised National Cancer Institute-sponsored Working Group Guidelines	Descriptive data will be computed and compared using analysis of variance and non-parametric rank equivalents for continuous data and chi-square or Fisher's exact test for discrete data.	Up to 2 years	No