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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Sorafenib

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02214
      • Dana-Farber Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Dana-Farber Cancer Institute
• Investigators: Principal Investigator: Yi-Bin Chen, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Chen YB, Li S, Lane AA, Connolly C, Del Rio C, Valles B, Curtis M, Ballen K, Cutler C, Dey BR, El-Jawahri A, Fathi AT, Ho VT, Joyce A, McAfee S, Rudek M, Rajkhowa T, Verselis S, Antin JH, Spitzer TR, Levis M, Soiffer R. Phase I trial of maintenance sorafenib after allogeneic hematopoietic stem cell transplantation for fms-like tyrosine kinase 3 internal tandem duplication acute myeloid leukemia. Biol Blood Marrow Transplant. 2014 Dec;20(12):2042-8. doi: 10.1016/j.bbmt.2014.09.007. Epub 2014 Sep 17.

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: July 19, 2011
• First Submitted That Met QC Criteria: July 19, 2011
• First Posted (Estimate): July 20, 2011

Study Record Updates

• Last Update Posted (Actual): March 22, 2017
• Last Update Submitted That Met QC Criteria: March 21, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: AML; Stem cell transplant; FLT3-ITD
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: 11-114