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Alvocidib in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
This study has been terminated.
Sponsor:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00377104
First received: September 13, 2006
Last updated: July 1, 2013
Last verified: July 2013
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Purpose
This phase I trial is studying the side effects and best dose of flavopiridol in treating patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma. Drugs used in chemotherapy, such as alvocidib, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.
| Condition | Intervention | Phase |
|---|---|---|
| B-cell Chronic Lymphocytic Leukemia Contiguous Stage II Small Lymphocytic Lymphoma Noncontiguous Stage II Small Lymphocytic Lymphoma Stage I Chronic Lymphocytic Leukemia Stage I Small Lymphocytic Lymphoma Stage II Chronic Lymphocytic Leukemia Stage III Chronic Lymphocytic Leukemia Stage III Small Lymphocytic Lymphoma Stage IV Chronic Lymphocytic Leukemia Stage IV Small Lymphocytic Lymphoma | Drug: alvocidib Other: pharmacological study Other: laboratory biomarker analysis | Phase 1 |
| Study Type: | Interventional |
| Study Design: | Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
| Official Title: | A Phase I Dose-Escalation Study of Flavopiridol (NSC 649890) Administered as a 30 Minute Loading Dose Followed by a 4-Hour Infusion in Patients With B-Cell Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) Following Cytoreduction With Chemotherapy |
Resource links provided by NLM:
Genetic and Rare Diseases Information Center resources:
Lymphosarcoma
Chronic Lymphocytic Leukemia
Leukemia, B-cell, Chronic
U.S. FDA Resources
Further study details as provided by National Cancer Institute (NCI):
Primary Outcome Measures:
- Toxicity profile of alvocidib administered as a 30 minute loading dose followed by a 4-hour infusion once weekly for 3 consecutive weeks every 5 weeks as consolidation therapy following cytoreduction chemotherapy [ Time Frame: Day 1, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment ]Assessed utilizing the NCI Common Terminology Criteria for Adverse Events version 3.0.
- Dose-limiting toxicity of alvocidib as consolidation chemotherapy after cytoreduction chemotherapy in patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma [ Time Frame: Course 1 ]The National Cancer Institute Common Toxicity Criteria version 3.0 will be used to characterize toxicity. If no patients experience dose-limiting toxicity, dose escalation will occur. If 1 patient has a dose limiting toxicity, 3 additional patients will be enrolled at that dose. If fewer than 2 of 6 patients experiences dose limiting toxicity, then the next highest dose level will be used for the subsequent cohort of 3 patients. If at any dose level two or more of the six patients experience a dose limiting toxicity, 3 additional patients will be treated at the previous dose level.
Secondary Outcome Measures:
- Pharmacokinetics and cellular pharmacodynamics of alvocidib administered in this schedule [ Time Frame: Baseline and day 1 ]Cytokine studies will be examined by standard ELISA assays to determine if increase IL-6 correlates with hypotension, hypoxemia, and tachycardia observed following treatment and to identify the source of production of this cytokine. We will examine interphase cytogenetics, p53 mutational status, p53/ATM functional assay, VH mutational status, and ZAP-70 over-expression.
- Complete response (CR) and overall response rate (CR and partial response) of alvocidib in patients with previously-treated CLL [ Time Frame: Baseline, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment ]Criteria for response will utilize the Revised National Cancer Institute-sponsored Working Group Guidelines.
| Enrollment: | 24 |
| Study Start Date: | September 2006 |
| Primary Completion Date: | November 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment (chemotherapy)
Patients receive alvocidib IV over 30 minutes (loading dose), followed by alvocidib IV over 4 hours on days 1, 8, and 15. Treatment repeats every 5 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
|
Drug: alvocidib
Given IV
Other Names:
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies
|
Detailed Description:
PRIMARY OBJECTIVES:
I. Determine the toxicity profile, dose-limiting toxicity, and maximum tolerated dose of flavopiridol (alvocidib) as consolidation chemotherapy after cytoreduction chemotherapy in patients with B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.
SECONDARY OBJECTIVES:
I. Determine the pharmacokinetics and cellular pharmacodynamics of flavopiridol in these patients.
II. Determine the complete response (CR) and overall response rate (CR and partial response) of patients treated with flavopiridol.
OUTLINE: This is a dose-escalation study. Patients receive alvocidib intravenously (IV) over 30 minutes (loading dose), followed by alvocidib IV over 4 hours on days 1, 8, and 15.
Treatment repeats every 5 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. 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. A total of 12 patients are treated at the MTD (i.e., recommended phase II dose). Patients undergo blood collection at baseline and periodically during study for pharmacokinetic and cytokine studies (levels of tumor necrosis factor-alpha, interleukin [IL]-6, -11, and -16) by enzyme-linked immunosorbent assay (ELISA). Interphase cytogenetics, p53 mutational status, p53/ATM function, V_H mutational status, zeta-chain-associated protein kinase 70 (ZAP-70) overexpression, and single nucleotide polymorphisms are also examined.
After completion of study treatment, patients are followed at 2 months and then every 3 months for 5 years.
Eligibility| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
-
Diagnosis of 1 of the following:
- B-cell chronic lymphocytic leukemia (CLL)
- Small lymphocytic lymphoma (SLL)
-
Must have received 1-3 prior therapies for CLL
- Completed therapy 2-12 months ago
- Prior therapy must have led to a partial response or greater
- No evidence of progressive disease
- ECOG performance status 0-2
- Absolute neutrophil count ≥ 1,000/mm³
- WBC ≤ 5,000/mm³
- Platelet count ≥ 50,000/mm³
- Cytopenia allowed
- Creatinine < 2.0 mg/dL
- Bilirubin ≤ 1.5 times normal (unless due to Gilbert's disease or hemolysis)
- AST ≤ 2 times normal (unless due to hemolysis)
- No secondary malignancy or other disease that would limit survival to < 2 years
- No history of inflammatory bowel disease unless inactive for > 2 years
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- See Disease Characteristics
- No other concurrent chemotherapy
- No concurrent radiotherapy
- No concurrent dexamethasone or other corticosteroid-based antiemetics
- No concurrent chronic corticosteroid therapy
-
No other concurrent hormonal therapy except for the following:
- Steroids for new adrenal failure
- Hormones for nondisease-related conditions (e.g., insulin for diabetes)
Contacts and Locations
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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00377104
Please refer to this study by its ClinicalTrials.gov identifier: NCT00377104
Locations
| United States, Ohio | |
| Ohio State University Medical Center | |
| Columbus, Ohio, United States, 43210 | |
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Leslie Andritsos | Ohio State University |
More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00377104 History of Changes |
| Obsolete Identifiers: | NCT01645579 |
| Other Study ID Numbers: |
NCI-2009-00161 OSU 05116 OSU-IRB-2006C0031 CDR0000501975 OSU-05116 U01CA076576 ( U.S. NIH Grant/Contract ) |
| Study First Received: | September 13, 2006 |
| Last Updated: | July 1, 2013 |
Additional relevant MeSH terms:
|
Leukemia, Lymphocytic, Chronic, B-Cell Lymphoma Leukemia Leukemia, Lymphoid Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases |
Leukemia, B-Cell Alvocidib Antineoplastic Agents Growth Inhibitors Growth Substances Physiological Effects of Drugs Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on September 21, 2017