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Flavopiridol in Treating Patients With Chronic Lymphocytic Leukemia or Prolymphocytic Leukemia

This study has been terminated.
(CTEP Initiated Action.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00098371
First received: December 7, 2004
Last updated: August 31, 2016
Last verified: August 2016
Results First Received: July 14, 2015  
Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: B-cell Chronic Lymphocytic Leukemia
Prolymphocytic Leukemia
Refractory Chronic Lymphocytic Leukemia
Intervention: Drug: alvocidib

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Treatment (Alvocidib) 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.To improve tolerability of treatment regimen, an amendment to the protocol was done to reduce the cycle length from 42 days to 28 days, reducing the number of treatments per cycle from four (days 1, 8, 15 & 22) to three (days 1, 8, and 15).

Participant Flow:   Overall Study
    Treatment (Alvocidib)
STARTED   64 
COMPLETED   64 
NOT COMPLETED   0 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
Treatment (Alvocidib) 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.

Baseline Measures
   Treatment (Alvocidib) 
Overall Participants Analyzed 
[Units: Participants]
 64 
Age 
[Units: Patients]
 
<=18 years   0 
Between 18 and 65 years   44 
>=65 years   20 
Age 
[Units: Years]
Median (Full Range)
 60 
 (31 to 82) 
Gender 
[Units: Patients]
 
Female   22 
Male   42 
Region of Enrollment 
[Units: Participants]
 
United States   64 


  Outcome Measures
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1.  Primary:   Complete Response (CR) Rate   [ Time Frame: Up to 8 months ]

2.  Primary:   Overall Response Rate (CR + PR)   [ Time Frame: Up to 8 months ]

3.  Primary:   Response Duration   [ Time Frame: Up to 8 months ]

4.  Primary:   Progression-free Survival (PFS) for Responding Patients as Assessed Using Standard Kaplan-Meier Methods   [ Time Frame: Up to 5 years ]

5.  Primary:   Progression-free Survival for All Patients as Assessed Using Standard Kaplan-Meier Methods   [ Time Frame: Up to 5 years ]

6.  Primary:   Overall Survival   [ Time Frame: Up to 5 years ]

7.  Primary:   Toxicity   [ Time Frame: Measurement prior to each infusion, at end of therapy, 2 months post-completion and post-treatment follow-up every 3 months for two years. ]

8.  Secondary:   Pharmacokinetics (PK) (AUC) as Assessed by Plasma Levels of Both Flavopiridol and Metabolites of Flavopiridol   [ Time Frame: During treatment day 1 and day 8 of cycle 1 ]

9.  Secondary:   PK (Cmax) as Assessed by Plasma Levels of Both Flavopiridol and Metabolites of Flavopiridol   [ Time Frame: During treatment day 1 and day 8 of course 1 ]

10.  Secondary:   PK as Assessed by Levels of Both Flavopiridol and Metabolites of Flavopiridol in Urine Samples   [ Time Frame: Urine collected at 4 separate times in some patients during the first 24 hours after start of infusion on day 1 of course 1. ]

11.  Secondary:   Serial Levels of IL-6 as Assessed by Blood Plasma   [ Time Frame: 4.5 hours, 8 hours, 12 hours, and 24 hours following the initiation of therapy during day 1 of course 1 ]

12.  Secondary:   Comparison of CLL Cell Samples Taken at Registration/Diagnosis to CLL Cell Samples Taken at Time of Relapse   [ Time Frame: At baseline and at time of relapse or when patient goes off therapy due to disease progression ]

13.  Secondary:   Correlation of Adverse Prognostic Factors With Response to Flavopiridol Treatment as Assessed by Interphase Cytogenetics, VH Mutational Status, ZAP-70 Protein Expression, CD38, and p53   [ Time Frame: up to 8 months ]

14.  Secondary:   Levels of Mcl-1 mRNA, Mcl-1 Protein, HIF-1alpha Protein, HIF-1alpha mRNA, NF-kappaB Activation, Total IkB, IkB Phosphorylation, GSK-beta Activity, and IL-6 Target Genes (i.e., STAT3)   [ Time Frame: At baseline, 4.5 hours (end of continuous infusion), 8 hours, and approximately 24 hours following initiation of therapy ]

15.  Secondary:   Comparison of Clinical Response and Tumor Lysis in Vivo With Drug-induced Apoptosis and Mitochondrial Perturbation in Vitro as Assessed by Flow Cytometry   [ Time Frame: At baseline ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: John Byrd, MD
Organization: The Ohio State University Comprehensive Cancer Center
phone: 614-293-9869
e-mail: John.Byrd@osumc.edu


Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00098371     History of Changes
Other Study ID Numbers: NCI-2009-00111
OSU 0491
N01CM62207 ( US NIH Grant/Contract Award Number )
Study First Received: December 7, 2004
Results First Received: July 14, 2015
Last Updated: August 31, 2016
Health Authority: United States: Food and Drug Administration