Flavopiridol in Treating Patients With Chronic Lymphocytic Leukemia or Prolymphocytic Leukemia - Full Text View

Sponsors and Collaborators:	Chronic Lymphocytic Leukemia Research Consortium National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00098371

Purpose

RATIONALE: Drugs used in chemotherapy, such as flavopiridol, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well flavopiridol works in treating patients with chronic lymphocytic leukemia or prolymphocytic leukemia.

Condition	Intervention	Phase
Leukemia	Drug: alvocidib	Phase II

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Alvocidib Flavopiridol

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Complete response (CR) and overall response rate (CR and partial response) [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]
Response duration [ Designated as safety issue: No ]
Progression-free survival [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Pharmacokinetics (PK) [ Designated as safety issue: No ]
Relationship of drug induced apoptosis of CLL cells in vitro to clinical response and tumor lysis in vivo [ Designated as safety issue: No ]
Variability of PK and pharmacodynamic analyses [ Designated as safety issue: No ]
Mechanisms of acquired flavopiridol resistance [ Designated as safety issue: No ]

Estimated Enrollment:	70
Study Start Date:	May 2005
Estimated Primary Completion Date:	August 2006 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

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.
Determine the toxicity profile of this drug in these patients.
Determine the response duration, progression-free survival, and overall survival of patients treated with this drug.
Determine the pharmacokinetics of this drug in these patients.

Secondary

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.
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.
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.

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.

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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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/mm^3 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/mm^3)
- 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)

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/mm^3

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00098371

Locations

United States, California
Rebecca and John Moores UCSD Cancer Center	Recruiting
La Jolla, California, United States, 92093-0658
Contact: Clinical Trials Office - Rebecca and John Moores UCSD Cancer 858-822-5354 cancercto@ucsd.edu
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02115
Contact: John G. Gribben, MD, DSc 617-632-3033 john_gribben@dfci.harvard.edu
United States, Minnesota
Mayo Clinic Cancer Center	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Office - All Mayo Clinic Locations 507-538-7623
United States, New York
Long Island Jewish Medical Center	Recruiting
New Hyde Park, New York, United States, 11040
Contact: Kanti R. Rai, MD 718-470-7135 rai@lij.edu
United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Recruiting
Columbus, Ohio, United States, 43210-1240
Contact: Clinical Trials Office - OSU Comprehensive Cancer Center 614-293-4976 osu@emergingmed.com
United States, Tennessee
Sarah Cannon Cancer Center at Centennial Medical Center	Recruiting
Nashville, Tennessee, United States, 37203
Contact: Clinical Trials Office - Sarah Cannon Cancer Center at Centenn 615-329-7274
United States, Texas
M. D. Anderson Cancer Center at University of Texas	Recruiting
Houston, Texas, United States, 77030-4009
Contact: Clinical Trials Office - M. D. Anderson Cancer Center at the U 713-792-3245

Sponsors and Collaborators

Chronic Lymphocytic Leukemia Research Consortium

National Cancer Institute (NCI)

Investigators

Study Chair:

John C. Byrd, MD

Arthur G. James Cancer Hospital & Richard J. Solove Research Institute

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Featured trial article This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000404350, CLLRC-OSU-0491, NCI-7000, OSU-0491
Study First Received:	December 7, 2004
Last Updated:	November 21, 2008
ClinicalTrials.gov Identifier:	NCT00098371
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

B-cell chronic lymphocytic leukemia
prolymphocytic leukemia
refractory chronic lymphocytic leukemia

Study placed in the following topic categories:

Chronic lymphocytic leukemia
Flavopiridol
Lymphatic Diseases
Leukemia
Leukemia, Lymphoid
Immunoproliferative Disorders

Leukemia, Prolymphocytic
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, B-cell, chronic
Prolymphocytic leukemia
Lymphoproliferative Disorders
Leukemia, B-Cell

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Antineoplastic Agents
Therapeutic Uses

Growth Substances
Physiological Effects of Drugs
Enzyme Inhibitors
Growth Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 13, 2009