Sorafenib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia
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
3 other identifiers
interventional
48
1 country
1
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 1, 2005
CompletedFirst Submitted
Initial submission to the registry
August 16, 2005
CompletedFirst Posted
Study publicly available on registry
August 19, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2007
CompletedJanuary 9, 2013
January 1, 2013
1.8 years
August 16, 2005
January 8, 2013
Conditions
Outcome Measures
Primary Outcomes (2)
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
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.
28 days
MDT based on the incidence of DTL as assessed by NCI-CTC version 3.0
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.
28 days
Secondary Outcomes (4)
Response (CR and/or PR)
Up to 1 year
Pharmacokinetic parameters
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
Sorafenib tosylate related adverse events as assessed by NCI-CTC version 3.0
Up to 1 year after completion of treatment
Impact of sorafenib tosylate on the Raf kinase/MEK/ERK signaling pathway
At baseline and at 28 days (course 1)
Study Arms (1)
Treatment (sorafenib tosylate)
EXPERIMENTALPatients 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.
Interventions
Given orally
Correlative studies
Eligibility Criteria
You may qualify if:
- Patients must have pathological confirmation (histologically or cytologically) of relapsed or refractory acute myeloid leukemia (other than acute promyelocytic leukemia), acute lymphocytic leukemia, or chronic myeloid leukemia in blast crisis
- The morphologic diagnosis of AML (non-APL), ALL, and CML in blast crisis will be made independently by members of the hematologic pathology division; routine staining and standard criteria as outlined by the Report of the NCI-Sponsored Workshop will be followed
- All patients must have been refractory to or relapsed from their most recent therapy AND are considered ineligible for potential curative approaches including allogeneic stem cell transplant; in addition, patients must be at least:
- weeks from last cytotoxic chemotherapy (excluding hydroxyurea)
- Hydroxyurea may be used for blast count control but must be discontinued within 48 hours of the initiation of BAY 43-9006
- weeks from last radiation therapy
- week from last biologic therapy (including myeloid growth factors)
- ECOG performance status =\< 2 (Karnofsky \>= 60%)
- Life expectancy of greater than 2 months
- Multilineage bone marrow failure due to the subject's underlying leukemia
- Total blast count in the peripheral blood \< 30,000
- Total bilirubin =\< 2 mg/dl
- AST(SGOT)/ALT(SGPT) =\< 5 X institutional upper limit of normal
- Serum creatinine within normal institutional limits OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
- All women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; the effects of BAY 43-9006 on the developing human fetus at the recommended therapeutic dose are unknown; however, kinase inhibitors are known to be teratogenic; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- +1 more criteria
You may not qualify if:
- Patients with APL are not eligible for this clinical trial
- Patients who have not recovered from adverse events due to agents administered more than 3 weeks earlier
- Patients with rapidly increasing peripheral blood blast counts (increase in the absolute peripheral blast count \> 50% within one week) or uncontrolled (absolute blast count \> 30,000) while on hydroxyurea will be excluded
- Patients with uncontrolled hypertension (i.e., persistent grade 3 while undergoing treatment)
- Patients may not be actively receiving any other investigational agents
- Patients active and / or untreated CNS leukemia will not be eligible
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to BAY 43-9006
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with BAY 43-9006
- Patients with immune deficiency are at increased risk of lethal infections when treated with marrow suppressive therapy; therefore, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with BAY 43-9006; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Patients must not have any evidence of bleeding diathesis
- Patients must not be on therapeutic anticoagulation; prophylactic anticoagulation (i.e. low dose warfarin) of venous or arterial access devices is allowed provided that the requirements for PT, INR or PTT are met
- Patients must not be taking the cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine, or phenobarbital), rifampin or St. John's wort
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Johns Hopkins University
Baltimore, Maryland, 21287-8936, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
B. Smith
Johns Hopkins University
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 16, 2005
First Posted
August 19, 2005
Study Start
June 1, 2005
Primary Completion
April 1, 2007
Last Updated
January 9, 2013
Record last verified: 2013-01