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

Sponsor
The University of Hong Kong (Other)
Overall Status
Completed
CT.gov ID
NCT03622541
Collaborator
(none)
46
Enrollment
1
Location
1
Arm
111.5
Actual Duration (Months)
0.4
Patients Per Site Per Month

Study Details

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
  • 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
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 :
Nov 15, 2010
Actual Primary Completion Date :
Dec 1, 2019
Actual Study Completion Date :
Mar 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 Names:
  • Sorafenib

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Complete remission (CR): [up to 16 weeks]

      count ≥ 100 x109/L.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
      1. Patients with AML carrying Flt3 mutation; AND,
      1. 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

    Site City State Country Postal Code
    1 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    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:
    Aug 9, 2018
    Last Update Posted:
    Mar 30, 2020
    Last Verified:
    Mar 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    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
    Sorafenib

    Study Results

    No Results Posted as of Mar 30, 2020