Using Sorafenib as a Salvage Treatment for Relapsed or Refractory Acute Myeloid Leukemia Carrying FLT3-ITD

NCT ID: NCT03622541

Last Updated: 2020-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-15
• Study Completion Date: 2020-03-01

Brief Summary

Patients with refractory or relapsed acute myeloid leukemia (AML) after two courses of standard chemotherapy regimens have very limited options. Further chemotherapy is associated with significant toxicity and is generally ineffective. About 10-30% patients with AML carry a gain-of-function mutation of a gene known as Flt3 in the leukemic cells, conferring them with abnormal cellular proliferation. Sorafenib is a multi-kinase inhibitor which was licensed in Hong Kong for the treatment of advanced hepatocellular and renal cell carcinoma. The drug has also been shown to be effective against Flt3 and AML but it has not been licensed for use in this condition.

Detailed Description

AML is one of the most lethal cancers among young people in Hong Kong. Induction chemotherapy is the mainstay of treatment, resulting in remission (i.e. clearance of leukemic cells) in 70% cases. Patients who fail induction chemotherapy or who relapse after initial remission would need to receive further chemotherapy with a view to achieve a second remission. Those who do so can be potentially cured by bone marrow transplantation (BMT). Those who fail are left with very little options. As a result, only 30% patients can survive long-term.

AML is heterogeneous and 10-30% patients carry a gain-of-function mutation of a gene known as fms-related tyrosine kinase-3 (Flt3) in the leukemic cells, which confers them with abnormal cellular proliferation. These patients have inferior prognosis compared with those without the mutation. With conventional chemotherapy, these leukemias often fail to remit, precluding patients from receiving curative BMT. Sorafenib is a multi-kinase inhibitor which is FDA approved for the treatment of metastatic hepatocellular and renal cell carcinomas. It is also effective against Flt3 and has been shown to be very effective in inducing remission in patients with AML carrying Flt3 mutation.

This proposal aims to treat relapsed or refractory AML patients carrying Flt3 mutation in the following ways:

1. Patients who have persistent or refractory leukemia after at least two prior chemotherapy regimens will receive sorafenib to induce a remission, hence bridging them to BMT for curative treatment.

2. Patients who relapse after BMT will receive sorafenib to induce remission again in preparation for second BMT.

3. Patients who are not candidates for BMT but have persistent or refractory leukemia after at least two prior chemotherapy regimens will receive sorafenib to induce a remission, followed by chemotherapy consolidation. Sorafenib induction will have significantly less side-effects compared with induction by conventional chemotherapy.

Patients who are treated with sorafenib will be managed in the hospital and out-patient clinics in the same way as patients undergoing induction by conventional chemotherapy. They will have bone marrow examinations before and one month after receiving sorafenib treatment

Conditions

FLT3-ITD Mutation; AML

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

sorafenib

Group Type: EXPERIMENTAL

Sorafenib 200mg

Intervention Type: DRUG

Sorafenib is a multi-kinase inhibitor which is FDA approved for the treatment of metastatic hepatocellular and renal cell carcinomas.

Interventions

Sorafenib 200mg

Sorafenib is a multi-kinase inhibitor which is FDA approved for the treatment of metastatic hepatocellular and renal cell carcinomas.

Intervention Type: DRUG

Other Intervention Names

Sorafenib

Eligibility Criteria

Inclusion Criteria

• 1. Patients with AML carrying Flt3 mutation; AND,
• 2. Patients with persistent leukemia despite at least two prior chemotherapy regimens

Exclusion Criteria

• Patients who are considered not fit for any form of leukemia treatment by the attending hematologists

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Dr. Anskar Y.H. Leung

clinical professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anskar Leung

Role: PRINCIPAL_INVESTIGATOR

The University of Hong Kong

Locations

The University of Hong Kong

Hong Kong, , Hong Kong

Countries

Hong Kong

Other Identifiers

AML004

Identifier Type: -

Identifier Source: org_study_id