Clinical Trial: Sorafenib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase I Dose Escalation Trial of the Raf Kinase Inhibitor BAY 43-9006 (NSC #724772) as Single Agent for Adults With Relapsed and Refractory Acute Leukemias and Chronic Myeloid Leukemia in Blast Crisis

Brief Summary: This phase I trial is studying the side effects and best dose of sorafenib in treating patients with relapsed or refractory acute myeloid leukemia, acute lymphoblastic leukemia, or chronic myelogenous leukemia. Sorafenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the dose-limiting toxicity(s) (DLTs) and maximally tolerated dose (MTD) of BAY 43-9006 given orally.

SECONDARY OBJECTIVES:

I. To obtain preliminary evidence of tumor response to BAY 43-9006 in patients. II. To assess the pharmacokinetic profile of BAY 43-9006. III. To characterize the preliminary profile of adverse events and changes in laboratory parameters in patients treated with BAY 43-9006.

IV. To assess effects of BAY 43-9006 on various cellular properties of leukemic blasts exposed to drug in vivo and in vitro.

OUTLINE: This is an open-label, dose-escalation study.

Patients receive oral sorafenib twice daily on days 1-14 or 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete remission (CR) may be considered for retreatment with sorafenib for up to an additional 6 courses upon disease recurrence provided the duration of CR is longer than 1 month.

Cohorts of 3-6 patients receive escalating doses of sorafenib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A total of 12 patients are treated at the MTD.

After completion of study treatment, patients are followed monthly for up to 1 year.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • DLT defined as non-hematologic > grade 3 or hematologic grade 4 marrow aplasia > 28 days (without leukemia clearance) as assessed by NCI-CTC version 3.0 [ Time Frame: 28 days ]
    Observed toxicities will be reported and summarized s with frequencies, type and grade in a descriptive manner. No formal statistical inference will be made on this dose-finding study.
  • MDT based on the incidence of DTL as assessed by NCI-CTC version 3.0 [ Time Frame: 28 days ]
    Observed toxicities will be reported and summarized s with frequencies, type and grade in a descriptive manner. No formal statistical inference will be made on this dose-finding study.


Original Primary Outcome:

Current Secondary Outcome:

  • Response (CR and/or PR) [ Time Frame: Up to 1 year ]
    Summarized in different dose levels and durations. The 95% confidence intervals will be provided.
  • Pharmacokinetic parameters [ Time Frame: At baseline, at 0.25, 0.5, 1, 2, 4, 6, 8, 24, and 48 hours (days 1, 2, and 3) at days 8, 15, and 29 ]
    Pharmacokinetic parameters over time in different dose levels will be evaluated via descriptive statistics.
  • Sorafenib tosylate related adverse events as assessed by NCI-CTC version 3.0 [ Time Frame: Up to 1 year after completion of treatment ]
    Adverse events will be summarized with frequencies by type and grade in different dose levels and durations using descriptive statistics.
  • Impact of sorafenib tosylate on the Raf kinase/MEK/ERK signaling pathway [ Time Frame: At baseline and at 28 days (course 1) ]
    Mean percentage changes will be estimated along with 95% confidence intervals. Dichotomous outcome (on/off) will be tabulated and proportions of activation between pre and post treatment will be compared using Fisher's exact test for each of those targets involved in Raf kinase signaling pathway.


Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: August 16, 2005
Date Started: June 2005
Date Completion:
Last Updated: January 8, 2013
Last Verified: January 2013