ClinicalTrials.gov
ClinicalTrials.gov Menu

Using Sorafenib as a Salvage Treatment for Relapsed or Refractory Acute Myeloid Leukemia Carrying FLT3 Internal Tandem Duplication (ITD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03622541
Recruitment Status : Recruiting
First Posted : August 9, 2018
Last Update Posted : August 9, 2018
Sponsor:
Information provided by (Responsible Party):
The University of Hong Kong

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 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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
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
Estimated Primary Completion Date : November 2018
Estimated Study Completion Date : November 2019



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


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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03622541


Locations
Hong Kong
The University of Hong Kong Recruiting
Hong Kong, Hong Kong
Contact: Chunxiao Zhang, SC    852-22554361    chunxiao@hku.hk   
Sponsors and Collaborators
The University of Hong Kong

Responsible Party: The University of Hong Kong
ClinicalTrials.gov Identifier: NCT03622541     History of Changes
Other Study ID Numbers: AML004
First Posted: August 9, 2018    Key Record Dates
Last Update Posted: August 9, 2018
Last Verified: August 2018
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
Leukemia, Myeloid, Acute
Leukemia
Neoplasms by Histologic Type
Neoplasms
Sorafenib
Niacinamide
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs