Expired Study
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Columbus, Ohio 43210


Purpose:

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.


Study summary:

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.


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 0-2 - See Disease Characteristics - WBC 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 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


Study is Available At:


Original ID:

NCI-2012-01435


NCT ID:

NCT00058240


Secondary ID:

NCI-2012-01435


Study Acronym:


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)


Overall Status:

Completed


Study Phase:

Phase 1/Phase 2


Genders:

Both


Minimum Age:

18 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

National Cancer Institute (NCI)


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Endpoint Classification: Safety Study, Interventio


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

84


Enrollment Type:

Actual


Overall Contact Information

Official Name:John Byrd
Principal Investigator
Ohio State University

Study Dates

Start Date:April 2003
Completion Date:February 2009
Completion Type:Actual
Primary Completion Date:February 2009
Primary Completion Type:Actual
Verification Date:November 2012
Last Changed Date:June 6, 2014
First Received Date:April 7, 2003

Study Outcomes

Outcome Type:Secondary Outcome
Measure:Overall response rate (CR + PR) of flavopiridol in patients evaluated utilizing the Revised National Cancer Institute-sponsored Working Group Guidelines
Time Frame:Up to 2 years
Safety Issues:False
Description:Descriptive data will be computed and compared using analysis of variance and non-parametric rank equivalents for continuous data and chi-square or Fisher's exact test for discrete data.
Outcome Type:Primary Outcome
Measure:Maximum tolerated dose of flavopiridol determined by dose-limiting toxicities graded assessed utilizing the NCI Common Toxicity Criteria 2.0
Time Frame:6 weeks
Safety Issues:True

Study Interventions

Intervention Type:Drug
Name:alvocidib
Description:Given IV
Arm Name:Arm I
Other Name:FLAVO

Study Arms

Study Arm Type:Experimental
Arm Name: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.

Study Agencies

Agency Class:NIH
Agency Type:Lead Sponsor
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Results Reference
Citation:Ni W, Ji J, Dai Z, Papp A, Johnson AJ, Ahn S, Farley KL, Lin TS, Dalton JT, Li X, Jarjoura D, Byrd JC, Sadee W, Grever MR, Phelps MA. Flavopiridol pharmacogenetics: clinical and functional evidence for the role of SLCO1B1/OATP1B1 in flavopiridol disposition. PLoS One. 2010 Nov 1;5(11):e13792.
PMID:21072184
Reference Type:Results Reference
Citation:Phelps MA, Lin TS, Johnson AJ, Hurh E, Rozewski DM, Farley KL, Wu D, Blum KA, Fischer B, Mitchell SM, Moran ME, Brooker-McEldowney M, Heerema NA, Jarjoura D, Schaaf LJ, Byrd JC, Grever MR, Dalton JT. Clinical response and pharmacokinetics from a phase 1 study of an active dosing schedule of flavopiridol in relapsed chronic lymphocytic leukemia. Blood. 2009 Mar 19;113(12):2637-45. Epub 2008 Nov 3.
PMID:18981292
Reference Type:Results Reference
Citation: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.

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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