Flavopiridol in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia or Lymphocytic Lymphoma - Full Text View

Sponsors and Collaborators:	Arthur G. James Cancer Hospital & Richard J. Solove Research Institute National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00058240

Purpose

RATIONALE: Drugs used in chemotherapy such as flavopiridol work in different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: This phase I trial is studying the side effects and best dose of flavopiridol in treating patients with previously treated chronic lymphocytic leukemia or lymphocytic lymphoma.

Condition	Intervention	Phase
Leukemia Lymphoma	Drug: alvocidib	Phase I

Study Type:	Interventional
Study Design:	Treatment
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)

Resource links provided by NLM:

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

Drug Information available for: Alvocidib Flavopiridol

U.S. FDA Resources

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

Estimated Enrollment:	84
Study Start Date:	April 2003
Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the maximum tolerated dose of flavopiridol in patients with previously treated B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.
Determine the dose-limiting toxicity and toxicity profile of this drug in these patients.
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.
Determine the pharmacokinetics and cellular pharmacodynamics of this drug in these patients.

Secondary

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

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.

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

Eligibility

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

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/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

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2

Life expectancy

Not specified

Hematopoietic

See Disease Characteristics
WBC less than 200,000/mm^3

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00058240

Locations

United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
Columbus, Ohio, United States, 43210-1240

Sponsors and Collaborators

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

National Cancer Institute (NCI)

Investigators

Study Chair:

Thomas S. Lin, MD, PhD

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

More Information

Additional Information:

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

Publications:

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.

Study ID Numbers:	CDR0000287197, OSU-0055, OSU 0055, NCI-5746
Study First Received:	April 7, 2003
Last Updated:	June 19, 2009
ClinicalTrials.gov Identifier:	NCT00058240 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

B-cell chronic lymphocytic leukemia
refractory chronic lymphocytic leukemia
Waldenstrom macroglobulinemia
recurrent small lymphocytic lymphoma

Study placed in the following topic categories:

Leukemia, Lymphoid
Immunoproliferative Disorders
Protein Kinase Inhibitors
Recurrence
Leukemia
Lymphatic Diseases
Flavopiridol

Waldenstrom Macroglobulinemia
Chronic Lymphocytic Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, B-Cell
Lymphoproliferative Disorders
Leukemia, B-cell, Chronic
Lymphoma

Additional relevant MeSH terms:

Leukemia, Lymphoid
Neoplasms by Histologic Type
Immunoproliferative Disorders
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions

Leukemia
Lymphatic Diseases
Flavopiridol
Neoplasms
Leukemia, Lymphocytic, Chronic, B-Cell
Therapeutic Uses
Growth Inhibitors
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphoma

ClinicalTrials.gov processed this record on July 02, 2009