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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


Phase 1
18 Years
N/A
Open (Enrolling)
Both
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

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Trial Information

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


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.


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)

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Description:

Assessed utilizing the NCI Common Terminology Criteria for Adverse Events version 3.0.

Outcome Time Frame:

Day 1, every 2 courses, at 2 months and then every 3 months for 5 years after completion of study treatment

Safety Issue:

Yes

Principal Investigator

Leslie Andritsos

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University Comprehensive Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00161

NCT ID:

NCT00377104

Start Date:

September 2006

Completion Date:

Related Keywords:

  • 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
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Lymphoma

Name

Location

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical CenterColumbus, Ohio  43210-1240