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A Dose-Escalation Study of Flavopiridol (NSC 649890) Administered as a 30 Minute Loading Dose Followed by a 4-Hour Infusion in Patients With Previously Treated B-Cell Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)


Phase 1
18 Years
N/A
Not Enrolling
Both
B-cell Chronic Lymphocytic Leukemia, Recurrent Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia, Waldenström Macroglobulinemia

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Trial Information

A Dose-Escalation Study of Flavopiridol (NSC 649890) Administered as a 30 Minute Loading Dose Followed by a 4-Hour Infusion in Patients With Previously Treated B-Cell Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)


PRIMARY OBJECTIVES:

I. To determine the toxicity profile, dose-limiting toxicity, and maximum tolerated dose of
flavopiridol administered as a 30 minute loading dose followed by a 4-hour infusion once
weekly for 4 consecutive weeks every 6 weeks.

II. To determine the safety and feasibility of performing dose escalation to 80 mg/m2 (30
mg/m2 30-minute IV bolus followed by 50 mg/m2 4-hour IV infusion) beginning dose 2 in
patients who do not experience severe tumor lysis requiring hemodialysis during dose 1.

III. To determine the pharmacokinetics and cellular pharmacodynamics of flavopiridol
administered in this schedule.

SECONDARY OBJECTIVES:

I. To determine the complete response (CR) and overall response rate (CR + PR) of
flavopiridol in patients with previously-treated CLL administered as a 30 minute loading
dose followed by a 4 hour infusion once weekly for 4 consecutive weeks every 6 weeks.

OUTLINE: This is a dose-escalation study.

Patients receive a loading dose of flavopiridol IV over 30 minutes followed by a 4-hour
infusion on days 1, 8, 15, and 22. Treatment repeats every 6 weeks for up to 6 courses in
the absence of unacceptable toxicity or disease progression.

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. After the MTD is determined, 12 additional
patients are accrued and treated as above at the recommended phase II dose.

After completion of study treatment, patients are followed at 2 months and then every 3
months for 2 years.


Inclusion Criteria:



- Diagnosis of B-cell chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma,
including Waldenstrom's macroglobulinemia, as indicated by the following:

- Massive or progressive splenomegaly and/or lymphadenopathy

- Anemia (hemoglobin less than 11 g/dL) or thrombocytopenia (platelet count less
than 100,000/mm^3)

- Weight loss of more than 10% within the past 6 months

- Grade 2 or 3 fatigue

- Fevers greater than 100.5º C or night sweats for more than 2 weeks with no
evidence of infection

- Progressive lymphocytosis with an increase of more than 50% over a 2-month
period or anticipated doubling time of less than 6 months

- Received at least 1 prior therapy for CLL

- Performance status - ECOG 0-2

- See Disease Characteristics

- WBC less than 200,000/mm^3

- Bilirubin no greater than 1.5 times normal (unless due to Gilbert's disease or any of
the conditions stated below)*

- AST no greater than 2 times normal*

- Creatinine no greater than 2.0 mg/dL

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No other malignancy that would limit survival to less than 2 years

- No history of inflammatory bowel disease (e.g., Crohn's disease or ulcerative
colitis) unless inactive for more than 2 years

- No psychiatric condition that would preclude compliance with treatment or giving
informed consent

- No other concurrent chemotherapy

- No concurrent chronic corticosteroids

- No concurrent hormonal therapy except steroids for new adrenal failure or hormonal
agents for nondisease-related conditions (e.g., insulin for diabetes)

- No concurrent dexamethasone or other corticosteroid-based antiemetics

- No concurrent radiotherapy

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Maximum tolerated dose of flavopiridol determined by dose-limiting toxicities graded assessed utilizing the NCI Common Toxicity Criteria 2.0

Outcome Time Frame:

6 weeks

Safety Issue:

Yes

Principal Investigator

John Byrd

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-01435

NCT ID:

NCT00058240

Start Date:

April 2003

Completion Date:

Related Keywords:

  • B-cell Chronic Lymphocytic Leukemia
  • Recurrent Small Lymphocytic Lymphoma
  • Refractory Chronic Lymphocytic Leukemia
  • Waldenström Macroglobulinemia
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Lymphoma
  • Waldenstrom Macroglobulinemia

Name

Location

Ohio State University Medical CenterColumbus, Ohio  43210