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Phase II Study of Flavopiridol in Patients With Previously Treated B-Cell Chronic Lymphocytic Leukemia (CLL) or Prolymphocytic Leukemia Arising from CLL
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
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Protocol IDs
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Phase II
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Treatment
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Active
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18 and over
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NCI
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CLLRC-OSU-0491 7000, NCI-7000, NCT00098371, OSU-0491
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Special Category:
NCI Web site featured trial 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.
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 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 Patient Characteristics:
Age Performance status Life expectancy 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 Other - Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No other malignancy that would limit life expectancy
Expected Enrollment 70A total of 70 patients will be accrued for this study within 3.5-6.5 months. Outcomes Primary Outcome(s)Complete response (CR) and overall response rate (CR and partial response) Toxicity Response duration Progression-free survival Overall survival
Secondary Outcome(s)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 | | | | Trial Sites
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U.S.A. |
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California |
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La Jolla |
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| | | | | | | | Rebecca and John Moores UCSD Cancer Center |
| | Clinical Trials Office - Rebecca and John Moores UCSD Cancer Center | |
| Email:
cancercto@ucsd.edu |
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Massachusetts |
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Boston |
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| | | Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute |
| | Clinical Trials Office - Dana-Farber/Harvard Cancer Center | |
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Minnesota |
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Rochester |
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| | | Mayo Clinic Cancer Center |
| | Clinical Trials Office - All Mayo Clinic Locations | |
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New York |
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New Hyde Park |
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| | | Long Island Jewish Medical Center |
| | Kanti Rai, MD | Ph: | 718-470-7135 | | 800-371-7111 |
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| Email:
rai@lij.edu |
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Ohio |
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Columbus |
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| | | Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center |
| | Clinical Trials Office - OSU Comprehensive Cancer Center | |
| Email:
osu@emergingmed.com |
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Tennessee |
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Nashville |
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| | | Sarah Cannon Cancer Center at Centennial Medical Center |
| | Clinical Trials Office - Sarah Cannon Cancer Center at Centennial Medical Center | |
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Texas |
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Houston |
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| | | M. D. Anderson Cancer Center at University of Texas |
| | Clinical Trials Office - M. D. Anderson Cancer Center at the University of Texas | |
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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 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. Back to Top |
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