Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Flavopiridol in Treating Patients With Chronic Lymphocytic Leukemia or Prolymphocytic Leukemia

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Active 18 and over NCI CLLRC-OSU-0491 7000, NCI-7000, NCT00098371, OSU-0491

Special Category: NCI Web site featured trial

Objectives

1. Determine the complete response (CR) and overall response rate (CR and partial response) in patients with previously treated B-cell chronic lymphocytic leukemia (CLL) or prolymphocytic leukemia arising from CLL treated with flavopiridol.
2. Determine the toxicity profile of this drug in these patients.
3. Determine the response duration, progression-free survival, and overall survival of patients treated with this drug.
4. Determine the pharmacokinetics of this drug in these patients.

Secondary

1. Determine the relationship of drug induced apoptosis of CLL cells in vitro and subsequent relationship to clinical response and tumor lysis in vivo in patients treated with this drug.
2. Determine the day 1 and 8 of cycle 1 pharmacokinetics (PK) in patients who are dose escalated to determine the variability of PK and pharmacodynamic analyses between these two treatment administrations.
3. Determine the differences in diagnosis and relapse samples to investigate mechanisms of acquired flavopiridol resistance in primary CLL cells in patients treated with this drug.

Entry Criteria

Disease Characteristics:

• Histologically confirmed B-cell chronic lymphocytic leukemia (CLL) or prolymphocytic leukemia (PLL) arising from CLL
  • No de novo PLL
  • Lymphocyte count > 5,000/mm³ at some point since initial diagnosis of CLL
  • B-cells co-expressing CD5 AND CD19 or CD20
  • If no dim serum immunoglobulin or CD23 expression on leukemia cells, must be examined for cyclin D1 overexpression OR t(11;14) to rule out mantle cell lymphoma



• Requiring therapy, defined by any of the following:
  • Massive or progressive splenomegaly and/or lymphadenopathy
  • Anemia (hemoglobin < 11 g/dL) OR thrombocytopenia (platelet count < 100,000/mm³)
  • Weight loss > 10% within the past 6 months
  • Grade 2 or 3 fatigue
  • Fevers > 100.5°C or night sweats for > 2 weeks with no evidence of infection
  • Progressive lymphocytosis with an increase of > 50% over a 2-month period OR an anticipated doubling time < 6 months



• Received ≥ 1 prior chemotherapy regimen that included fludarabine or nucleoside equivalent OR alternative therapy if contraindication to fludarabine exists (i.e., autoimmune hemolytic anemia)

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• No other concurrent chemotherapy

Endocrine therapy

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

Radiotherapy

• No concurrent radiotherapy

Surgery

• Not specified

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 2 years

Hematopoietic

• See Disease Characteristics
• Baseline cytopenias allowed
• WBC ≤ 200,000/mm³

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN) (unless due to Gilbert's disease, hemolysis, or disease infiltration of the liver)
• AST ≤ 2 times ULN (unless due to hemolysis or disease infiltration of the liver)

Renal

• Creatinine ≤ 2.0 mg/dL

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy that would limit life expectancy

Expected Enrollment

A total of 70 patients will be accrued for this study within 3.5-6.5 months.

Outcomes

Complete response (CR) and overall response rate (CR and partial response)
Toxicity
Response duration
Progression-free survival
Overall survival

Pharmacokinetics (PK)
Relationship of drug induced apoptosis of CLL cells in vitro to clinical response and tumor lysis in vivo
Variability of PK and pharmacodynamic analyses
Mechanisms of acquired flavopiridol resistance

Outline

This is an open-label study.

Patients receive flavopiridol IV over 30 minutes followed by a 4-hour infusion on days 1, 8, 15, and 22. Treatment repeats every 42 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving at least a partial remission (PR) and whose PR lasts for > 6 months after completion of treatment may receive 6 additional courses of flavopiridol.

Patients are followed at 2 months and then every 3 months for 5 years.

Trial Contact Information

Trial Lead Organizations

Chronic Lymphocytic Leukemia Research Consortium

John Byrd, MD, Protocol chair		Ph: 614-293-9869 Email: john.byrd@osumc.edu

U.S.A.
California
	La Jolla
	Rebecca and John Moores UCSD Cancer Center
		Clinical Trials Office - Rebecca and John Moores UCSD Cancer Center	Ph:  858-822-5354
			Email: cancercto@ucsd.edu
Massachusetts
	Boston
	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
		Clinical Trials Office - Dana-Farber/Harvard Cancer Center	Ph:  617-582-8480
Minnesota
	Rochester
	Mayo Clinic Cancer Center
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
New York
	New Hyde Park
	Long Island Jewish Medical Center
		Kanti Rai, MD	Ph:  718-470-7135 800-371-7111
			Email: rai@lij.edu
Ohio
	Columbus
	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
		Clinical Trials Office - OSU Comprehensive Cancer Center	Ph:  614-293-4976
			Email: osu@emergingmed.com
Tennessee
	Nashville
	Sarah Cannon Cancer Center at Centennial Medical Center
		Clinical Trials Office - Sarah Cannon Cancer Center at Centennial Medical Center	Ph:  615-329-7274
Texas
	Houston
	M. D. Anderson Cancer Center at University of Texas
		Clinical Trials Office - M. D. Anderson Cancer Center at the University of Texas	Ph:  713-792-3245

Related Information

Featured trial article

Registry Information
Official Title		A Phase II CRC Study Of Flavopiridol Administered As A 30 Minute Loading Dose Followed By A 4-hour Continuous Infusion In Patients With Previously Treated B-Cell Chronic Lymphocytic Leukemia Or Prolymphocytic Leukemia Arising From CLL
Trial Start Date		2005-05-03
Trial Completion Date		2006-08-26 (estimated)
Registered in ClinicalTrials.gov		NCT00098371
Date Submitted to PDQ		2004-10-29
Information Last Verified		2008-10-24
NCI Grant/Contract Number		CA76576, CA1605