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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01398501
• Other study ID #: 11-114
• Status: Completed
• Phase: Phase 1
• First received: July 19, 2011
• Last updated: March 21, 2017
• Start date: August 2011
• Est. completion date: August 2016

Study information

• Verified date: March 2017
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: August 2016
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Sorafenib
Oral, 200 to 400 mg QD or BID

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Dana-Farber Cancer Institute

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 sorafe — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose	To define the maximum tolerated dose (MTD) of maintenance sorafenib after allogeneic HSCT	3 years
Secondary	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
Secondary	Rate of serious infections	Rate of serious infections (bacterial, viral, fungal, or other) after starting sorafenib	3 years
Secondary	Rate of acute GVHD	Rate of grades II-IV acute graft-vs-host disease (GVHD) after starting sorafenib	3 years
Secondary	Rate of chronic GVHD	Rates of significant chronic GVHD after starting sorafenib	3 years
Secondary	Survival	1-year and 2-year progression-free and overall survival after HSCT	3 years
Secondary	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