Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	NCI	OSU-0055 OSU 0055, NCI-5746, NCT00058240, 5746

Objectives

Primary

1. Determine the maximum tolerated dose of flavopiridol in patients with previously treated B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.
2. Determine the dose-limiting toxicity and toxicity profile of this drug in these patients.
3. Determine the safety and feasibility of performing dose escalation of this drug in patients who do not experience sever tumor lysis requiring hemodialysis during dose 1.
4. Determine the pharmacokinetics and cellular pharmacodynamics of this drug in these patients.

Secondary

1. Determine the complete response and overall response rates in patients treated with this drug.

Entry Criteria

Disease Characteristics:

• 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/mm³)
  • 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

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• No other concurrent chemotherapy

Endocrine therapy

• 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

Radiotherapy

• No concurrent radiotherapy

Surgery

• Not specified

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics
• WBC less than 200,000/mm³

Hepatic

• 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*

 [Note: *Unless due to hemolysis, disease infiltration of the liver, or perihepatic lymph node obstruction of biliary flow from the liver]

Renal

• Creatinine no greater than 2.0 mg/dL

Other

• 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

Expected Enrollment

Approximately 3-84 patients will be accrued for this study within 28 months.

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.

Phelps MA, Lin TS, Johnson AJ, et al.: Clinical response and pharmacokinetics from a phase 1 study of an active dosing schedule of flavopiridol in relapsed chronic lymphocytic leukemia. Blood 113 (12): 2637-45, 2009.[PUBMED Abstract]

Lin TS, Dalton JT, Wu D, et al.: Flavopiridol given as a 30-min intravenous (IV) bolus followed by 4-hr continuous IV infusion (CIVI) results in clinical activity and tumor lysis in refractory chronic lymphocytic leukemia (CLL). [Abstract] J Clin Oncol 22 (Suppl 14): A-6564, 573s, 2004.

Trial Contact Information

Trial Lead Organizations

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Thomas Lin, MD, PhD, Protocol chair		Ph: 614-293-5655 Email: thomas.lin@osumc.edu

Registry Information
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)
Trial Start Date		2003-04-21
Trial Completion Date		2009-02-23
Registered in ClinicalTrials.gov		NCT00058240
Date Submitted to PDQ		2003-02-25
Information Last Verified		2007-01-15
NCI Grant/Contract Number		CA81534, CA16058

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