Sorafenib Maintenance Therapy for Patients With AML After Allogeneic Stem Cell Transplant

Study Overview
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Brief Summary
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Sorfenib works by slowing the spread of cancer cells. It has been used in other studies for patients with AML with the FLT3-ITD mutation and information from these studies suggests that sorafenib may help to control leukemia. The purpose of this study is to find the highest dose of sorafenib for maintenance therapy that can be safely used in participants with AML who have undergone allogeneic stem cell transplant.

Detailed Description
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Subjects will taken sorafenib orally either once or twice daily. Subjects will come to the Bone Marrow Transplant Clinic 3 times (on Day 8, 15, and 30) during the first month of treatment. After the first month, they will be seen every month for 3 months and then at 9 at 6 and 9 months. Subjects will have a physical exam and be asked questions regarding general health and specific questions about any problems they might be having and any medications they are taking. Subjects will have standard blood tests every month for 12 months to check liver and kidney function and complete blood count. Subjects will have research blood tests on Days 8, 15 and 30 during the first month of treatment. Subjects will have a bone marrow biopsy after 3 months and 12 months of treatment. Subjects will receive treatment for up to 12 months and be followed for 1 year after completing the study.

Official Title
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Phase I Trial of Sorafenib Maintenance Therapy for Patients With FLT3-ITD AML After Allogeneic Stem Cell Transplantation

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Sorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with AML with the FLT3-ITD mutation who have undergone allogeneic HSCT Peripheral blood chimerism studies showing >/= 70% of all cells are of donor origin Adequate hematologic and hepatic function ECOG performance status 0-2 Able to swallow whole pills Exclusion Criteria: Evidence of relapsed/recurrent/residual disease as assessed by bone marrow aspirate and biopsy performed between days 30-60 after HSCT Active acute graft vs host disease requiring an equivalent dose of > 0.5 mg/kg/day of prednisone or equivalent or those patients which necessitated the addition of another agent for the treatment of GVHD beyond corticosteroids Ongoing uncontrolled infection Cardiac disease: congestive heart failure > class II NYHA, unstable angina or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy Uncontrolled hypertension Known HIV infection or chronic hepatitis B or C Thrombotic or embolic events such as cerebrovascular accident including transient ischemic attacks within the past 6 months Pulmonary hemorrhage/bleeding event > CTCAE v 4.0 Grade 2 within 4 weeks of starting study drug Any other hemorrhage/bleeding event > CTCAE v. 4.0 Grade 3 within 4 weeks of starting study drug Serious non-healing wound, non-healing ulcer, or bone fracture Evidence or history of bleeding diathesis or coagulopathy Major surgery or significant traumatic injury within 4 weeks of starting study drug Use of St. John's Wort or rifampin (rifampicin) Known or suspected allergy to sorafenib Pregnant or breast-feeding Receiving any other investigational agents

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Post-SCT Sorafenib<br>Sorafenib will be given as maintenance therapy after allo HCT to patients with FLT3-ITD AML. | Drug: Sorafenib<br>* Oral, 200 to 400 mg QD or BID<br>* Other names: BAY 43-9006;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose | To define the maximum tolerated dose (MTD) of maintenance sorafenib after allogeneic HSCT | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median number of days sorafenib tolerated | Define the median number of days of sorafenib tolerated prior to dose-limiting toxicity or disease relapse | 3 years | 
| Rate of serious infections | Rate of serious infections (bacterial, viral, fungal, or other) after starting sorafenib | 3 years | 
| Rate of acute GVHD | Rate of grades II-IV acute graft-vs-host disease (GVHD) after starting sorafenib | 3 years | 
| Rate of chronic GVHD | Rates of significant chronic GVHD after starting sorafenib | 3 years | 
| Survival | 1-year and 2-year progression-free and overall survival after HSCT | 3 years | 
| Impact of sorafenib on bone marrow and serum levels of FLT3-ITD quantitative PCR | To assess the impact of sorafenib on quantitative bone marrow and serum levels of FLT3-ITD DNA in patients (as measured by PCR) with FLT3-ITD AML after allogeneic SCT | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, FLT3-ITD, Stem cell transplant