Sorafenib Maintenance Therapy for Patients With AML After Allogeneic Stem Cell Transplant - Full Text View

Sponsor:	Massachusetts General Hospital
Collaborator:	Dana-Farber Cancer Institute
Information provided by (Responsible Party):	Yi-Bin A. Chen, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT01398501

Purpose

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.

Condition	Intervention	Phase
Acute Myeloid Leukemia	Drug: Sorafenib	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I Trial of Sorafenib Maintenance Therapy for Patients With FLT3-ITD AML After Allogeneic Stem Cell Transplantation

Resource links provided by NLM:

Genetics Home Reference related topics: familial acute myeloid leukemia with mutated CEBPA

MedlinePlus related topics: Acute Myeloid Leukemia Cancer Leukemia

Drug Information available for: Sorafenib Sorafenib tosylate

U.S. FDA Resources

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:

Maximum Tolerated Dose [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
To define the maximum tolerated dose (MTD) of maintenance sorafenib after allogeneic HSCT

Secondary Outcome Measures:

Median number of days sorafenib tolerated [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Define the median number of days of sorafenib tolerated prior to dose-limiting toxicity or disease relapse
Rate of serious infections [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
Rate of serious infections (bacterial, viral, fungal, or other) after starting sorafenib
Rate of acute GVHD [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
Rate of grades II-IV acute graft-vs-host disease (GVHD) after starting sorafenib
Rate of chronic GVHD [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
Rates of significant chronic GVHD after starting sorafenib
Survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
1-year and 2-year progression-free and overall survival after HSCT
Impact of sorafenib on bone marrow and serum levels of FLT3-ITD quantitative PCR [ Time Frame: 3 years ] [ Designated as safety issue: No ]
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

Estimated Enrollment:	28
Study Start Date:	August 2011
Estimated Study Completion Date:	August 2014
Estimated Primary Completion Date:	August 2014 (Final data collection date for primary outcome measure)

Intervention Details:

Oral, 200 to 400 mg QD or BID

Other Name: BAY 43-9006

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.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01398501

Contacts

Contact: Yi-Bin Chen, MD

617-724-1124

ychen6@partners.org

Locations

United States, Massachusetts
Massachusetts General Hospital	Recruiting
Boston, Massachusetts, United States, 02114
Principal Investigator: Yi-Bin Chen, MD
Dana-Farber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02214
Principal Investigator: Robert Soiffer, MD

Sponsors and Collaborators

Massachusetts General Hospital

Dana-Farber Cancer Institute

Investigators

Principal Investigator:

Yi-Bin Chen, MD

Massachusetts General Hospital

More Information

No publications provided

Responsible Party:	Yi-Bin A. Chen, MD, Physician, Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT01398501 History of Changes
Other Study ID Numbers:	11-114
Study First Received:	July 19, 2011
Last Updated:	April 26, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:

AML
FLT3-ITD
Stem cell transplant

Additional relevant MeSH terms:

Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Sorafenib

Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 23, 2012