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