Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Sorafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

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

Sorafenib 200mg

Anskar Leung

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

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 Internal Tandem Duplication (ITD)

The University of Hong Kong

clinical professor

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Hematinics

Liver Extracts

MTL-CEBPA administered weekly, twice weekly or thrice weekly over 3 weeks followed by 1 week of rest defining a 28-day cycle.

MTL-CEBPA is administered weekly or twice weekly in combination with sorafenib over 3 weeks followed by 1 week of rest defining a 28-day cycle.

MTL-CEBPA is administered weekly or twice weekly for 2 cycles (28-day cycle) followed by 2 cycles of sorafenib

MTL-CEBPA

Dr Debashis Sarker, MBChB, MRCP

Professor Nagy Habib, FRCS

MNA-3521-011 study is a multi-centre, open-label, first-in-human, phase 1a/b clinical study dose/dose frequency escalation followed by a cohort expansion part. MTL-CEBPA is administered as monotherapy or in combination with sorafenib to patients with advanced hepatocellular carcinoma and cirrhosis of the liver. All participants will be considered unsuitable for liver tumour resection and/or is refractory to radiotherapy and other loco-regional therapies.

MTL-CEBPA consists of a double stranded RNA formulated into a SMARTICLES® liposomal nanoparticle and is designed to activate the CEBPA gene.

First-in-Human Safety, Tolerability and Antitumour Activity Study of MTL-CEBPA in Patients With Advanced Liver Cancer

A First-in-Human, Multi-centre, Open-label, Phase 1a/b Clinical Study With RNA Oligonucleotide Drug MTL-CEBPA to Investigate Its Safety, Tolerability, and Antitumour Activity in Patients With Advanced Liver Cancer

Frequency of adverse events graded according to NCI CTCAE v5.0

Increase or decrease in tumour measurement using Response Evaluation Criteria in Solid Tumours (RECIST) reports

Frequency of treatment-related adverse events graded according to NCI CTCAE v5.0

Mina Alpha Limited

Neoplasms, Glandular and Epithelial

Adenocarcinoma

Participants receive SCT-I10A intravenously，200mg，d1，Q3w

SCT-I10A

Participants receive SCT510 intravenously，15mg/kg，d1，Q3w

SCT510

Participants receive sorafenib orally，400mg bid

The purpose of the study is to assess the safety and effectiveness of SCT-I10A in combination with SCT510 in patients with HCC who have not received prior systemic therapy.

SCT-I10A Plus SCT510 Versus Sorafenib as First-Line Therapy for Advanced Hepatocellular Carcinoma

SCT-I10A in Combination With SCT510 Versus Sorafenib as First-Line Therapy for Advanced Hepatocellular Carcinoma (HCC): A Multicenter, Randomized, Open-label,Phase 2/3 Trial

PFS evaluated by investigator based on RECIST V1.1

ORR evaluated by BICR based on RECIST V1.1.

ORR evaluated by investigator based on RECIST V1.1

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Using Sorafenib as a Salvage Treatment for Relapsed or Refractory Acute Myeloid Leukemia Carrying FLT3-ITD	NCT03622541	FLT3-ITD Mutati... AML	Sorafenib 200mg	18 Years -	The University of Hong Kong
First-in-Human Safety, Tolerability and Antitumour Activity Study of MTL-CEBPA in Patients With Advanced Liver Cancer	NCT02716012	Hepatocellular ... Liver Cancer	MTL-CEBPA Sorafenib 200mg	16 Years -	Mina Alpha Limited
SCT-I10A Plus SCT510 Versus Sorafenib as First-Line Therapy for Advanced Hepatocellular Carcinoma	NCT04560894	Hepatocellular ...	SCT-I10A SCT510 Sorafenib 200mg	18 Years -	Sinocelltech Ltd.

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