Sorafenib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia
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|ClinicalTrials.gov Identifier: NCT00131989|
Recruitment Status : Completed
First Posted : August 19, 2005
Last Update Posted : January 9, 2013
|Condition or disease||Intervention/treatment||Phase|
|Adult Acute Basophilic Leukemia Adult Acute Eosinophilic Leukemia Adult Acute Megakaryoblastic Leukemia (M7) Adult Acute Minimally Differentiated Myeloid Leukemia (M0) Adult Acute Monocytic Leukemia (M5b) Adult Acute Myeloblastic Leukemia With Maturation (M2) Adult Acute Myeloblastic Leukemia Without Maturation (M1) Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) Adult Acute Myeloid Leukemia With t(15;17)(q22;q12) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Adult Acute Myelomonocytic Leukemia (M4) Adult Erythroleukemia (M6a) Adult Pure Erythroid Leukemia (M6b) Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia||Drug: sorafenib tosylate Other: pharmacological study Other: laboratory biomarker analysis||Phase 1|
I. To determine the dose-limiting toxicity(s) (DLTs) and maximally tolerated dose (MTD) of BAY 43-9006 given orally.
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||48 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||June 2005|
|Actual Primary Completion Date :||April 2007|
Experimental: Treatment (sorafenib tosylate)
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 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.
Drug: sorafenib tosylate
Other: pharmacological study
Other Name: pharmacological studies
Other: laboratory biomarker analysis
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00131989
|United States, Maryland|
|Johns Hopkins University|
|Baltimore, Maryland, United States, 21287-8936|
|Principal Investigator:||B. Smith||Johns Hopkins University|