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Alvocidib in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00377104
First received: September 13, 2006
Last updated: April 10, 2013
Last verified: January 2013
History of Changes
  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
Genetic: cytogenetic analysis
Genetic: mutation analysis
Genetic: polymorphism analysis
Genetic: protein expression analysis
Other: diagnostic laboratory biomarker analysis
Other: immunoenzyme technique
Other: immunologic technique
Other: pharmacological study
 Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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:

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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Criteria for response will utilize the Revised National Cancer Institute-sponsored Working Group Guidelines.


Enrollment: 24
Study Start Date: September 2006
Estimated Primary Completion Date: June 2013 (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:
  • FLAVO
  • flavopiridol
  • HMR 1275
  • L-868275
Genetic: cytogenetic analysis
Correlative studies
Genetic: mutation analysis
Correlative studies
Genetic: polymorphism analysis
Correlative studies
Genetic: protein expression analysis
Correlative studies
Other: diagnostic laboratory biomarker analysis
Correlative studies
Other: immunoenzyme technique
Correlative studies
Other Name: immunoenzyme techniques
Other: immunologic technique
Correlative studies
Other Names:
  • immunological laboratory methods
  • laboratory methods, immunological
Other: pharmacological study
Correlative studies
Other Name: pharmacological 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
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00377104

Locations
United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at 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 Comprehensive Cancer Center
  More Information

No publications provided

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, U01CA076576
Study First Received: September 13, 2006
Last Updated: April 10, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
 Flavopiridol
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Growth Inhibitors
Growth Substances
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 16, 2013