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

• ClinicalTrials.gov Identifier: NCT03622541
• Recruitment Status: Completed
• First Posted: August 9, 2018
• Last Update Posted: March 30, 2020
• Sponsor: The University of Hong Kong
• Information provided by (Responsible Party): Dr. Anskar Y.H. Leung, The University of Hong Kong

Study Description

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.

Condition or disease	Intervention/treatment	Phase
FLT3-ITD Mutation; AML	Drug: Sorafenib 200mg	Phase 2

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 46 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Using Sorafenib as a Salvage Treatment for Relapsed or Refractory Acute Myeloid Leukemia Carrying FLT3 Internal Tandem Duplication (ITD)
• Actual Study Start Date: November 15, 2010
• Actual Primary Completion Date: December 1, 2019
• Actual Study Completion Date: March 1, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: sorafenib	Drug: Sorafenib 200mg; Sorafenib is a multi-kinase inhibitor which is FDA approved for the treatment of metastatic hepatocellular and renal cell carcinomas.; Other Name: Sorafenib

Outcome Measures

Primary Outcome Measures :

1. Complete remission (CR): [ Time Frame: up to 16 weeks ]
   count ≥ 100 x109/L.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Hong Kong

The University of Hong Kong

Hong Kong, Hong Kong

Sponsors and Collaborators

The University of Hong Kong

Investigators

• Principal Investigator: Anskar Leung; The University of Hong Kong

More Information

• Responsible Party: Dr. Anskar Y.H. Leung, clinical professor, The University of Hong Kong
• ClinicalTrials.gov Identifier: NCT03622541
• Other Study ID Numbers: AML004
• First Posted: August 9, 2018
• Last Update Posted: March 30, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Leukemia, Myeloid, Acute; Leukemia; Neoplasms by Histologic Type; Neoplasms; Leukemia, Myeloid; Sorafenib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action