AMLPhase 2NCT03170895
Combination of Sorafenib and Omacetaxine Mepesuccinate in Newly Diagnosed or Relapsed/Refractory AML Carrying FLT3-ITD
A Phase 2 study testing Sorafenib and Omacetaxine Mepesuccinate Injection in people with AML and FLT3-ITD Mutation, run by The University of Hong Kong at 1 site in Hong Kong.
Trial summary
The study aims to test if combination of sorafenib and omacetaxine mepesuccinate (OM, also known as homoharringtonine) results in durable composite complete remission (CRc) in patients with newly diagnosed or relapsed/refractory (R/R) acute myeloid leukemia (AML) carrying FLT3-ITD (Fms-Like Tyrosine Kinase 3 … Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- AML, FLT3-ITD Mutation
- What is being tested?
- Sorafenib and Omacetaxine Mepesuccinate Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteHong Kong
- Study dates
- 1 Jul 2017to 1 Mar 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of written informed consent approved by the Institutional Review Board (IRB).
- Age ≥18 years
- Documented primary AML or AML secondary to myelodysplastic syndrome (MDS), as defined by World Health Organization criteria
- At diagnosis or in morphological relapse after an initial remission or refractory after induction chemotherapy, with or without HSCT
- Documentation of FLT3-ITD in BM or blood with allelic burden of ≥ 20% as determined by the study site laboratory
- ECOG performance score 0-2
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- Serum creatinine ≤1.5×upper limit of normal (ULN), or glomerular filtration rate >25 mL/min, as calculated with the Cockcroft-Gault formula.
- Serum potassium, magnesium, and calcium (corrected for albumin) within institutional normal limits. Subjects with electrolytes outside the normal range will be eligible if these values are corrected upon retesting following any necessary supplementation.
- Total serum bilirubin ≤1.5×ULN.
- Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤ 2.5×ULN.
Who cannot join
- Acute promyelocytic leukemia (AML subtype M3)
- Prior treatment with any FLT3 inhibitors
- Known infection with human immunodeficiency virus, or active hepatitis B or C infection.
- Refusal of blood product transfusion.
- In a man whose sexual partner is a woman of childbearing potential, unwillingness or inability of the man or woman to use an acceptable contraceptive method for the entire study treatment period and for at least 3 months after study treatment completion
- In a heterosexually active woman of childbearing potential, unwillingness or inability to use an acceptable contraceptive method for the entire study treatment period and for at least 3 months after study treatment completion
- Pregnancy
- Female subjects must agree not to breastfeed at screening and throughout the study period, and for 45 days after the final study drug administration.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Single-arm Open-labeled Study Evaluating Combination of Sorafenib and Omacetaxine Mepesuccinate in Newly Diagnosed or Relapsed/Refractory AML Carrying FLT3-ITD
The study aims to test if combination of sorafenib and omacetaxine mepesuccinate (OM, also known as homoharringtonine) results in durable composite complete remission (CRc) in patients with newly diagnosed or relapsed/refractory (R/R) acute myeloid leukemia (AML) carrying FLT3-ITD (Fms-Like Tyrosine Kinase 3 - Internal Tandem Duplication).
Read the detailed description
The type of AML being studied in this clinical trial is known as FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) positive AML. This type of AML has an alteration (or mutation) in genes, which may associated with high risk of relapse after conventional chemotherapy and hence an extremely poor clinical outcome.
FLT3 inhibitors including sorafenib are effective in inducing remission. However, their effects are only transient. There is an unmet clinic need to enhance their effectiveness, hence clinical application.
This is a Phase II single-arm open-labeled study. A total of 40 eligible patients with consent will be recruited, including 20 patients with newly diagnosed and 20 with R/R FLT3-ITD AML.
For newly diagnosed patients, diagnostic bone marrow (BM) and/or peripheral blood (PB) will be evaluated by next generation sequencing (NGS) based on myeloid panel that comprises 54 myeloid genes as well as their in vitro response to sorafenib and omacetaxine mepesuccinate (OM) based on an in-house platform that was established in our laboratory. FLT3-ITD allelic burden will also be evaluated.
For R/R patients, FLT3-ITD status and allelic burden will be confirmed before treatment. Both groups of patients will receive sorafenib 400 mg twice daily continuously and OM 1.5 mg/m2 daily for 7 days every 28 days until progression or allogeneic hematopoietic stem cell transplantation (HSCT). Thereafter, patients will be followed up and information about disease status and survival will be collected. BM examination will be performed on day 28 to document morphological response and FLT3-ITD allelic burden.
At leukemia progression, BM and/or PB samples will be collected and their in vitro response to sorafenib and OM examined. The tyrosine kinase domain (TKD) of FLT3 will also be sequenced and FLT3-ITD allelic burden will be evaluated.
- Conditions
- AML, FLT3-ITD Mutation
- Being tested
- Sorafenib, Omacetaxine Mepesuccinate Injection
- Keywords
- FLT3-ITD (+) Acute Myeloid Leukemia (AML)
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SorafenibDrug
Also called NEXAVAR
Sorafenib a kinase inhibitor indicated for the treatment of Unresectable hepatocellular carcinoma; Advanced renal cell carcinoma
Omacetaxine Mepesuccinate InjectionDrug
Also called homoharringtonine
Omacetaxine Mepesuccinate is a pharmaceutical drug substance that is indicated for treatment of chronic myeloid leukemia (CML)
| Study group | Role | What they receive |
|---|---|---|
| sorafenib and Omacetaxine Mepesuccinate | Experimental | The starting dose of sorafenib will be 400 mg twice daily. Sorafenib should be taken continuously throughout the treatment period unless there is no evidence of response at first assessment on day 28 or progressive disease at any time during the treatment.
OM will be given at 1.5 mg/m2/day (maximum dose 3 mg) for 7 days (concurrently with sorafenib) in 28-day cycle.
Sorafenib and OM will be continued until leukemia progression or allogeneic HSCT. Thereafter, patients will be followed up and information about disease status and survival will be collected. Receives: Drug: Sorafenib; Drug: Omacetaxine Mepesuccinate Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete remission
No increase in blasts in BM or PB (<5% of total nucleated cells), with absolute neutrophil count ≥ 1x109/L and platelet count ≥ 100 x109/L
Measured: up to 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2017
- Study start1 Jul 2017
- Primary completion1 Feb 2020
- Study completion1 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AMLStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Anskar Y.H. Leung, The University of Hong Kong
- Investigators
- Anskar Leung, Professor, Principal investigator, The University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03170895
- Sponsor's protocol ID
- AML008
- Status last verified
- Mar 2020
- First submitted
- 26 May 2017
- Last updated
- 30 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Single-arm Open-labeled Study Evaluating Combination of Sorafenib and Omacetaxine Mepesuccinate in Newly Diagnosed or Relapsed/Refractory AML Carrying FLT3-ITD
- ClinicalTrials.gov ID
- NCT03170895
- Acronym / sponsor ID
- AML008
- Conditions
- AML, FLT3-ITD Mutation
- Keywords
- FLT3-ITD (+) Acute Myeloid Leukemia (AML)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Study start
- 1 Jul 2017 (actual)
- Primary completion
- 1 Feb 2020 (actual)
- Study completion
- 1 Mar 2020 (actual)
- First posted
- 31 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study aims to test if combination of sorafenib and omacetaxine mepesuccinate (OM, also known as homoharringtonine) results in durable composite complete remission (CRc) in patients with newly diagnosed or relapsed/refractory (R/R) acute myeloid leukemia (AML) carrying FLT3-ITD (Fms-Like Tyrosine Kinase 3 - Internal Tandem Duplication).
Detailed description
The type of AML being studied in this clinical trial is known as FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) positive AML. This type of AML has an alteration (or mutation) in genes, which may associated with high risk of relapse after conventional chemotherapy and hence an extremely poor clinical outcome.
FLT3 inhibitors including sorafenib are effective in inducing remission. However, their effects are only transient. There is an unmet clinic need to enhance their effectiveness, hence clinical application.
This is a Phase II single-arm open-labeled study. A total of 40 eligible patients with consent will be recruited, including 20 patients with newly diagnosed and 20 with R/R FLT3-ITD AML.
For newly diagnosed patients, diagnostic bone marrow (BM) and/or peripheral blood (PB) will be evaluated by next generation sequencing (NGS) based on myeloid panel that comprises 54 myeloid genes as well as their in vitro response to sorafenib and omacetaxine mepesuccinate (OM) based on an in-house platform that was established in our laboratory. FLT3-ITD allelic burden will also be evaluated.
For R/R patients, FLT3-ITD status and allelic burden will be confirmed before treatment. Both groups of patients will receive sorafenib 400 mg twice daily continuously and OM 1.5 mg/m2 daily for 7 days every 28 days until progression or allogeneic hematopoietic stem cell transplantation (HSCT). Thereafter, patients will be followed up and information about disease status and survival will be collected. BM examination will be performed on day 28 to document morphological response and FLT3-ITD allelic burden.
At leukemia progression, BM and/or PB samples will be collected and their in vitro response to sorafenib and OM examined. The tyrosine kinase domain (TKD) of FLT3 will also be sequenced and FLT3-ITD allelic burden will be evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| sorafenib and Omacetaxine Mepesuccinate | Experimental | Drug: Sorafenib, Drug: Omacetaxine Mepesuccinate InjectionThe starting dose of sorafenib will be 400 mg twice daily. Sorafenib should be taken continuously throughout the treatment period unless there is no evidence of response at first assessment on day 28 or progressive disease at any time during the treatment. OM will be given at 1.5 mg/m2/day (maximum dose 3 mg) for 7 days (concurrently with sorafenib) in 28-day cycle. Sorafenib and OM will be continued until leukemia progression or allogeneic HSCT. Thereafter, patients will be followed up and information about disease status and survival will be collected. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Provision of written informed consent approved by the Institutional Review Board (IRB).
- Age ≥18 years
- Documented primary AML or AML secondary to myelodysplastic syndrome (MDS), as defined by World Health Organization criteria
- At diagnosis or in morphological relapse after an initial remission or refractory after induction chemotherapy, with or without HSCT
- Documentation of FLT3-ITD in BM or blood with allelic burden of ≥ 20% as determined by the study site laboratory
Key exclusion criteria (8 listed)
- Acute promyelocytic leukemia (AML subtype M3)
- Prior treatment with any FLT3 inhibitors
- Known infection with human immunodeficiency virus, or active hepatitis B or C infection.
- Refusal of blood product transfusion.
- In a man whose sexual partner is a woman of childbearing potential, unwillingness or inability of the man or woman to use an acceptable contraceptive method for the entire study treatment period and for at least 3 months after study treatment completion
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SorafenibAlso: NEXAVARSorafenib a kinase inhibitor indicated for the treatment of Unresectable hepatocellular carcinoma; Advanced renal cell carcinoma | Drug | sorafenib and Omacetaxine Mepesuccinate |
| Omacetaxine Mepesuccinate InjectionAlso: homoharringtonineOmacetaxine Mepesuccinate is a pharmaceutical drug substance that is indicated for treatment of chronic myeloid leukemia (CML) | Drug | sorafenib and Omacetaxine Mepesuccinate |
Primary outcome
Complete remission
Time frame: up to 16 weeks
No increase in blasts in BM or PB (<5% of total nucleated cells), with absolute neutrophil count ≥ 1x109/L and platelet count ≥ 100 x109/L
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anskar Leung, Professor principal investigator
The University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sorafenib and Omacetaxine Mepesuccinate Injection in people with AML and FLT3-ITD Mutation, run by The University of Hong Kong at 1 site in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete remission (time frame: up to 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2020.