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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Dana-Farber Cancer Institute
Information provided by (Responsible Party):
Yi-Bin A. Chen, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01398501
First received: July 19, 2011
Last updated: February 11, 2014
Last verified: February 2014
  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:


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 2016
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 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

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02214
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: February 11, 2014
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 April 16, 2014