Core Binding Factor Acute Myeloid LeukemiaPhase 2NCT05404516
Combination of Sorafenib With Standard Therapy in Newly Diagnosed Adult CBF AML
A Phase 2 study testing Sorafenib, Idarubicin and Cytarabine in people with Core Binding Factor Acute Myeloid Leukemia, run by Nanfang Hospital, Southern Medical University at 1 site in China.
Trial summary
Core-binding factor acute myeloid leukemia accounts for 10-15% of AML and is categorized as favorable-risk AML. However, the 5-year CIR was up to 40% in this group of patients. Emerging data show that a high frequency of mutations and/or high expression of KIT in CBF AML. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Core Binding Factor Acute Myeloid Leukemia
- What is being tested?
- Sorafenib, Idarubicin and Cytarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2020to 31 Dec 2023
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have an unequivocal diagnosis of de novo-CBF AML, prior to start therapy, documented by rearrangement of Core Binding Factor (CBF) genes, namely RUNX1/RUNX1T1 and CBFB/MYH11.
- Age 18 to 65 years old with ECOG performance status 0-2.
- Sign informed consent form, have the ability to comply with study and follow-up procedures.
- Patients must have Total Bilirubin ≤ 1.5 x ULN, and AST or ALT ≤ 2.5 x ULN.
- Patients must have Serum Creatinine ≤ 1.5 x ULN.
- Women of child-bearing potential must have a negative pregnancy test before starting the protocol.
Who cannot join
- Prior therapy for AML with the following exceptions:
- emergency leukapheresis
- emergency treatment for hyperleukocytosis with hydroxyurea for ≤ 7 days.
- Central nervous system involvement.
- Presence of any uncontrolled bacterial, viral or fungal infection.
- Known human immunodeficiency virus (HIV) positive.
Show all 16Show fewer
- An active Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection. Patients whose disease is controlled under antiviral therapy should not be excluded.
- Presence of other active malignancies.
- QTc > 470 msec (Bazett formula) on screening ECG.
- Presence of significant uncontrolled or active cardiovascular disease, specifically including, but not restricted to:
- Myocardial infarction, unstable angina and/or congestive heart failure within 3 months prior to randomization
- History of clinically significant (as determined by the treating physician) atrial arrhythmia or any ventricular arrhythmia
- Uncontrolled hypertension
- Taking medications that are known to be associated with Torsades de Pointes.
- History of hypersensitivity to any drugs or metabolites of similar chemical classes as the study treatment.
- Intolerance to sorafenib, namely persistence of sorafenib-related adverse events despite supportive treatment, persistence or recurrence of adverse events after dose interruption or dose reduction of sorafenib, or both of these.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Department of Hematology,Nanfang Hospital, Southern Medical University
Guangzhou, Guangdong, 510515
Pengcheng Shi, shpch283@163.com
Qifa Liu
About this study
Official title: Prospective Evaluation of Sorafenib Combined With Standard Therapy in Newly Diagnosed Adult Core-binding Factor Acute Myeloid Leukemia: an Open-label , Randomised Controlled, Multicenter Phase II Trial
Core-binding factor acute myeloid leukemia accounts for 10-15% of AML and is categorized as favorable-risk AML. However, the 5-year CIR was up to 40% in this group of patients. Emerging data show that a high frequency of mutations and/or high expression of KIT in CBF AML. Sorafenib is a multitargeted TKI, thus the purpose of this study is to evaluate the safety and efficacy of sorafenib combined with standard therapy in CBF AML.
Read the detailed description
Core-binding factor acute myeloid leukemia is characterized by t(8;21) or inv(16) and accounts for 10-15% of AML. Because of the high CR rate of nearly 90% and a 5-year OS of almost 50%, CBF-AML is categorized as favorable-risk AML. However, the 5-year cumulative incidence of relapse (CIR) was up to 40% in this group of patients after high-dose cytarabine consolidation following CR. Therefore, more effective therapeutic approaches are needed.
Emerging data show that a high frequency of mutations and/or high expression of KIT in CBF AML likely result in aberrant tyrosine kinase activity, leukemia cell growth and survival, and treatment resistance. Thus, pharmacologic inhibition of KIT would lead to significant antileukemia activity if combined with an optimized chemotherapy regimen in patients with CBF AML. Recent mechanistic findings also support the potential clinical benefit of KIT inhibition in CBF AML.
Sorafenib is a first-generation type-II multitargeted tyrosine kinase receptor inhibitor (TKI) that suppresses various signaling pathways associated with the development of AML, such as RTK (FLT3, c-KIT), RAS/RAF, vascular endothelial growth factor (VEGF) receptor. The purpose of this study is to evaluate the safety and efficacy of sorafenib combined with standard therapy in CBF AML.
- Being tested
- Sorafenib, Idarubicin, Cytarabine
- Keywords
- Core Binding Factor Acute Myeloid Leukemia, Sorafenib, CMR (Complete Molecular Remission)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SorafenibDrug
Induction cycle(s): 400 mg BID on days 8-21.
Consolidation cycles 1-4: 400 mg BID on days 1-21.
Maintenance therapy: 400 mg BID for one year.
IdarubicinDrug
Induction cycle(s): 12 mg/m2/day on days 1-3.
Consolidation cycle 1: 8 mg/m2/day administered on days 1-3.
CytarabineDrug
Induction cycle(s): 100 mg/m2 by continuous IV infusion for 24 hours on days 1-7.
Consolidation cycles 1-4: 2 g/m2/12h on days 1-3.
| Study group | Role | What they receive |
|---|---|---|
| Sorafenib | Experimental | Induction cycle(s):
IA3+7. Patients will receive sorafenib 400 mg BID on days 8-21.
Consolidation Cycle 1:
IA3+3. Patients will receive sorafenib 400 mg BID on days 1-21.
Consolidation Cycles 2-4:
MDAC. Patients will receive sorafenib 400 mg BID on days 1-21.
Maintenance therapy:
Single agent sorafenib 400 mg BID for one year. Receives: Drug: Sorafenib; Drug: Idarubicin; Drug: Cytarabine |
| Standard therapy | Active comparator | Induction cycle(s):
IA3+7.
Consolidation Cycle 1:
IA3+3.
Consolidation Cycles 2-4:
MDAC. Receives: Drug: Idarubicin; Drug: Cytarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
CMR (Complete Molecular Remission)
CMR in BM after 4 cycles of chemotherapies
Measured: 1 year
Secondary outcomes (4)
Overall survival
Measured: 3 year
Leukemia-free survival
Measured: 3 year
Cumulative incidence of relapse
Measured: 3 year
Adverse effects
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2022
- Study start1 Jan 2020
- Primary completion31 Aug 2022 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Core Binding Factor Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Nanfang Hospital, Southern Medical UniversityThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 88 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nanfang Hospital, Southern Medical University
- Sponsor type
- University, hospital or other
- Collaborators
- Guangzhou First People's Hospital, Guangzhou Panyu Central Hospital, Institute of Hematology & Blood Diseases Hospital, China, Peking University People's Hospital, Shenzhen Hospital of Southern Medical University, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
- Responsible party
- Principal investigator, Qifa Liu, Nanfang Hospital, Southern Medical University
- Investigators
- Qifa Liu, Principal investigator, Nanfang Hospital, Southern Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05404516
- Sponsor's protocol ID
- Sorafenib-CBF AML-2022
- Status last verified
- May 2022
- First submitted
- 31 May 2022
- Last updated
- 3 Jun 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Rucker FG, Agrawal M, Corbacioglu A, Weber D, Kapp-Schwoerer S, Gaidzik VI, Jahn N, Schroeder T, Wattad M, Lubbert M, Koller E, Kindler T, Gotze K, Ringhoffer M, Westermann J, Fiedler W, Horst HA, Greil R, Schroers R, Mayer K, Heinicke T, Krauter J, Schlenk RF, Thol F, Heuser M, Ganser A, Bullinger L, Paschka P, Dohner H, Dohner K. Measurable residual disease monitoring in acute myeloid leukemia with t(8;21)(q22;q22.1): results from the AML Study Group. Blood. 2019 Nov 7;134(19):1608-1618. doi: 10.1182/blood.2019001425.
PubMed 31554635Paschka P, Schlenk RF, Weber D, Benner A, Bullinger L, Heuser M, Gaidzik VI, Thol F, Agrawal M, Teleanu V, Lubbert M, Fiedler W, Radsak M, Krauter J, Horst HA, Greil R, Mayer K, Kundgen A, Martens U, Heil G, Salih HR, Hertenstein B, Schwanen C, Wulf G, Lange E, Pfreundschuh M, Ringhoffer M, Girschikofsky M, Heinicke T, Kraemer D, Gohring G, Ganser A, Dohner K, Dohner H. Adding dasatinib to intensive treatment in core-binding factor acute myeloid leukemia-results of the AMLSG 11-08 trial. Leukemia. 2018 Jul;32(7):1621-1630. doi: 10.1038/s41375-018-0129-6. Epub 2018 Apr 17.
PubMed 29720733Rollig C, Serve H, Huttmann A, Noppeney R, Muller-Tidow C, Krug U, Baldus CD, Brandts CH, Kunzmann V, Einsele H, Kramer A, Schafer-Eckart K, Neubauer A, Burchert A, Giagounidis A, Krause SW, Mackensen A, Aulitzky W, Herbst R, Hanel M, Kiani A, Frickhofen N, Kullmer J, Kaiser U, Link H, Geer T, Reichle A, Junghanss C, Repp R, Heits F, Durk H, Hase J, Klut IM, Illmer T, Bornhauser M, Schaich M, Parmentier S, Gorner M, Thiede C, von Bonin M, Schetelig J, Kramer M, Berdel WE, Ehninger G; Study Alliance Leukaemia. Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2015 Dec;16(16):1691-9. doi: 10.1016/S1470-2045(15)00362-9. Epub 2015 Nov 6.
PubMed 26549589
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Evaluation of Sorafenib Combined With Standard Therapy in Newly Diagnosed Adult Core-binding Factor Acute Myeloid Leukemia: an Open-label , Randomised Controlled, Multicenter Phase II Trial
- ClinicalTrials.gov ID
- NCT05404516
- Acronym / sponsor ID
- Sorafenib-CBF AML-2022
- Keywords
- Core Binding Factor Acute Myeloid Leukemia, Sorafenib, CMR (Complete Molecular Remission)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 88 participants (estimated)
- Lead sponsor
- Nanfang Hospital, Southern Medical UniversityUniversity, hospital or other
- Collaborators
- Guangzhou First People's Hospital, Guangzhou Panyu Central Hospital, Institute of Hematology & Blood Diseases Hospital, China, Peking University People's Hospital, Shenzhen Hospital of Southern Medical University, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
- Study start
- 1 Jan 2020 (actual)
- Primary completion
- 31 Aug 2022 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 3 Jun 2022 (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.
Core-binding factor acute myeloid leukemia accounts for 10-15% of AML and is categorized as favorable-risk AML. However, the 5-year CIR was up to 40% in this group of patients. Emerging data show that a high frequency of mutations and/or high expression of KIT in CBF AML. Sorafenib is a multitargeted TKI, thus the purpose of this study is to evaluate the safety and efficacy of sorafenib combined with standard therapy in CBF AML.
Detailed description
Core-binding factor acute myeloid leukemia is characterized by t(8;21) or inv(16) and accounts for 10-15% of AML. Because of the high CR rate of nearly 90% and a 5-year OS of almost 50%, CBF-AML is categorized as favorable-risk AML. However, the 5-year cumulative incidence of relapse (CIR) was up to 40% in this group of patients after high-dose cytarabine consolidation following CR. Therefore, more effective therapeutic approaches are needed.
Emerging data show that a high frequency of mutations and/or high expression of KIT in CBF AML likely result in aberrant tyrosine kinase activity, leukemia cell growth and survival, and treatment resistance. Thus, pharmacologic inhibition of KIT would lead to significant antileukemia activity if combined with an optimized chemotherapy regimen in patients with CBF AML. Recent mechanistic findings also support the potential clinical benefit of KIT inhibition in CBF AML.
Sorafenib is a first-generation type-II multitargeted tyrosine kinase receptor inhibitor (TKI) that suppresses various signaling pathways associated with the development of AML, such as RTK (FLT3, c-KIT), RAS/RAF, vascular endothelial growth factor (VEGF) receptor. The purpose of this study is to evaluate the safety and efficacy of sorafenib combined with standard therapy in CBF AML.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sorafenib | Experimental | Drug: Sorafenib, Drug: Idarubicin, Drug: CytarabineInduction cycle(s): IA3+7. Patients will receive sorafenib 400 mg BID on days 8-21. Consolidation Cycle 1: IA3+3. Patients will receive sorafenib 400 mg BID on days 1-21. Consolidation Cycles 2-4: MDAC. Patients will receive sorafenib 400 mg BID on days 1-21. Maintenance therapy: Single agent sorafenib 400 mg BID for one year. |
| Standard therapy | Active comparator | Drug: Idarubicin, Drug: CytarabineInduction cycle(s): IA3+7. Consolidation Cycle 1: IA3+3. Consolidation Cycles 2-4: MDAC. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients must have an unequivocal diagnosis of de novo-CBF AML, prior to start therapy, documented by rearrangement of Core Binding Factor (CBF) genes, namely RUNX1/RUNX1T1 and CBFB/MYH11.
- Age 18 to 65 years old with ECOG performance status 0-2.
- Sign informed consent form, have the ability to comply with study and follow-up procedures.
- Patients must have Total Bilirubin ≤ 1.5 x ULN, and AST or ALT ≤ 2.5 x ULN.
- Patients must have Serum Creatinine ≤ 1.5 x ULN.
Key exclusion criteria (16 listed)
- Prior therapy for AML with the following exceptions:
- Central nervous system involvement.
- Presence of any uncontrolled bacterial, viral or fungal infection.
- Known human immunodeficiency virus (HIV) positive.
- An active Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection. Patients whose disease is controlled under antiviral therapy should not be excluded.
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 |
|---|---|---|
| SorafenibInduction cycle(s): 400 mg BID on days 8-21. Consolidation cycles 1-4: 400 mg BID on days 1-21. Maintenance therapy: 400 mg BID for one year. | Drug | Sorafenib |
| IdarubicinInduction cycle(s): 12 mg/m2/day on days 1-3. Consolidation cycle 1: 8 mg/m2/day administered on days 1-3. | Drug | Sorafenib, Standard therapy |
| CytarabineInduction cycle(s): 100 mg/m2 by continuous IV infusion for 24 hours on days 1-7. Consolidation cycles 1-4: 2 g/m2/12h on days 1-3. | Drug | Sorafenib, Standard therapy |
Primary outcome
CMR (Complete Molecular Remission)
Time frame: 1 year
CMR in BM after 4 cycles of chemotherapies
4 secondary outcomes
Overall survival
Time frame: 3 year
Leukemia-free survival
Time frame: 3 year
Cumulative incidence of relapse
Time frame: 3 year
Adverse effects
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2022.
- Background: PubMed 31554635Rucker FG, Agrawal M, Corbacioglu A, Weber D, Kapp-Schwoerer S, Gaidzik VI, Jahn N, Schroeder T, Wattad M, Lubbert M, Koller E, Kindler T, Gotze K, Ringhoffer M, Westermann J, Fiedler W, Horst HA, Greil R, Schroers R, Mayer K, Heinicke T, Krauter J, Schlenk RF, Thol F, Heuser M, Ganser A, Bullinger L, Paschka P, Dohner H, Dohner K. Measurable residual disease monitoring in acute myeloid leukemia with t(8;21)(q22;q22.1): results from the AML Study Group. Blood. 2019 Nov 7;134(19):1608-1618. doi: 10.1182/blood.2019001425.
- Background: PubMed 29720733Paschka P, Schlenk RF, Weber D, Benner A, Bullinger L, Heuser M, Gaidzik VI, Thol F, Agrawal M, Teleanu V, Lubbert M, Fiedler W, Radsak M, Krauter J, Horst HA, Greil R, Mayer K, Kundgen A, Martens U, Heil G, Salih HR, Hertenstein B, Schwanen C, Wulf G, Lange E, Pfreundschuh M, Ringhoffer M, Girschikofsky M, Heinicke T, Kraemer D, Gohring G, Ganser A, Dohner K, Dohner H. Adding dasatinib to intensive treatment in core-binding factor acute myeloid leukemia-results of the AMLSG 11-08 trial. Leukemia. 2018 Jul;32(7):1621-1630. doi: 10.1038/s41375-018-0129-6. Epub 2018 Apr 17.
- Background: PubMed 26549589Rollig C, Serve H, Huttmann A, Noppeney R, Muller-Tidow C, Krug U, Baldus CD, Brandts CH, Kunzmann V, Einsele H, Kramer A, Schafer-Eckart K, Neubauer A, Burchert A, Giagounidis A, Krause SW, Mackensen A, Aulitzky W, Herbst R, Hanel M, Kiani A, Frickhofen N, Kullmer J, Kaiser U, Link H, Geer T, Reichle A, Junghanss C, Repp R, Heits F, Durk H, Hase J, Klut IM, Illmer T, Bornhauser M, Schaich M, Parmentier S, Gorner M, Thiede C, von Bonin M, Schetelig J, Kramer M, Berdel WE, Ehninger G; Study Alliance Leukaemia. Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2015 Dec;16(16):1691-9. doi: 10.1016/S1470-2045(15)00362-9. Epub 2015 Nov 6.
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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.
Qifa Liu principal investigator
Nanfang Hospital, Southern Medical University
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, Idarubicin and Cytarabine in people with Core Binding Factor Acute Myeloid Leukemia, run by Nanfang Hospital, Southern Medical University at 1 site in China.
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 6 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 3 Jun 2022. 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 China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Pengcheng Shi (+86-020-62787883, shpch283@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CMR (Complete Molecular Remission) (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05404516, which also lists 3 linked publications.
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 3 Jun 2022.