Brief Title
Flavopiridol in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia or Lymphocytic Lymphoma
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)
Brief 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.
Detailed 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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Number of Patients With Dose Limiting Toxicities (DLTs)
Secondary Outcome
Overall Response Rate (CR + PR) of Flavopiridol in Patients Evaluated Utilizing the Revised National Cancer Institute-sponsored Working Group Guidelines
Condition
B-cell Chronic Lymphocytic Leukemia
Intervention
alvocidib
Study Arms / Comparison Groups
Arm I
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
52
Start Date
April 2003
Completion Date
February 2009
Primary Completion Date
February 2009
Eligibility Criteria
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 (Eastern Cooperative Oncology Group) 0-2
- See Disease Characteristics
- WBC (white blood count) 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 (aspartate aminotransferase) 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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
John Byrd, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00058240
Organization ID
NCI-2012-01435
Secondary IDs
NCI-2012-01435
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
John Byrd, Principal Investigator, Ohio State University
Verification Date
June 2017