CML,Blast PhasePhase 1/2NCT06757855
Olverembatinib Combined With Venetoclax and Azacitidine in Blast Phase Ph Chromosome-positive CML
A Phase 1/2 study testing Olverembatinib, Venetoclax and Azacitidine in people with CML,Blast Phase, run by Institute of Hematology & Blood Diseases Hospital, China at 1 site in China.
Trial summary
Even in the TKI era, the outcoms of patients with blast phase is still poor.The response rate to conventional intensive chemotherapy is only 12.5% and the 5-year survival rate is 0 for patients with myeloid blast crsis. Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- CML,Blast Phase
- What is being tested?
- Olverembatinib, Venetoclax and Azacitidine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteChina
- Study dates
- 26 Jan 2025to 1 Dec 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with t(9;22)(q34;q11)/BCR::ABL1 positive blast-phase CML who are aged 15 years or older, whether initially in the blast phase or progressing from the chronic phase, with no gender restriction.
- Blast phase criteria: Conforming to the 2022 WHO criteria for CML Blast phase: bone marrow or peripheral blood blast cells ≥ 20%; for diagnosis of acute lymphoblastic transformation, if the immature lymphoblasts (determined by immunophenotype) ≥ 5% according to the ICC 2022 criteria; blast cell aggregation in bone marrow or extramedullary tissues.
- ECOG performance status score ≤ 2.
- Major organ function assessment criteria: Total bilirubin < 1.5×upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5×ULN; serum creatinine < 2×ULN; myocardial enzymes < 2×ULN; serum amylase ≤ 1.5×ULN; left ventricular ejection fraction (LEF) within the normal range on echocardiography.
- Men and women of reproductive potential agree and adopt effective contraceptive measures.
- The informed consent form is signed by the patient himself/herself or an immediate family member. Considering the patient's condition, if the patient's signature is not conducive to the control of the disease, the legal guardian or an immediate family member of the patient signs the informed consent form.
Who cannot join
- Before group entry, other systemic anti-cancer treatments for acute transformation were received (excluding single-agent TKI, hormone, or hydroxyurea for reducing tumor burden before group entry, and single-agent olverembatinib ≤ 14 days)
- Myocardial infarction occurred within 12 months before enrollment in this study; other clinically significant cardiac diseases (such as unstable angina, congestive heart failure, uncontrollable hypertension, uncontrollable arrhythmia, etc.)
- Uncontrolled active severe infection
- Known positive serum HIV
- Acute pancreatitis occurred within 1 year before study screening, or a history of chronic pancreatitis
- Uncontrolled hypertriglyceridemia (triglycerides > 450 mg/dL, i.e., 5.1 mmol/L) or hypercholesterolemia (total cholesterol (TC) ≥ 6.2 mmol/L)
Show all 12Show fewer
- Another malignancy diagnosed and treated within 5 years before diagnosis, or previously diagnosed with another malignancy with evidence of residual disease. Patients with non-melanoma skin cancer or any type of carcinoma in situ, if completely resected, should not be excluded
- Pregnant or lactating women
- Clinical manifestations of CNS leukemia or extramedullary infiltration
- Uncontrolled diabetes, defined as glycated hemoglobin value > 7.5%. Patients with previously existing but well-controlled diabetes need not be excluded
- Mental illness that may prevent the subject from completing treatment or providing informed consent
- Other conditions considered unsuitable for this study by the investigator
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Blood Diseases Hospital
Tianjin, Tianjin Municipality, 300020
Hui Wei, MD, 86-13132507161, weihui@ihcams.ac.cn
About this study
Official title: A Multicenter, Single-arm I/II Clinical Study of Olverembatinib Combined With Venetoclax and Azacitidine in in Blast Phase Ph Chromosome- Chronic Myeloid Leukemia
Even in the TKI era, the outcoms of patients with blast phase is still poor.The response rate to conventional intensive chemotherapy is only 12.5% and the 5-year survival rate is 0 for patients with myeloid blast crsis. The response rate of TKI monotherapy is about 50% and the response rate is further improved when combined TKI and chemotherapy for patients with lymphoid blast crsis. The induction remission rate of chemotherapy alone for patients with Ph-positive acute lymphoblastic leukemia is 50-60%, and the remission rate increases to more than 95% when combined with TKI. Therefore, the application of TKI for patients in the blast crisis phase is of great significance. Olverembatinib is the only third-generation TKI drug approved in the Chinese mainland at present. Preclinical research data show that olverembatinib has a significant inhibitory effect on wild-type and mutant ABL resistant to the first and second-generation TKIs, as well as some complex mutations resistant to ponatinib. Phase I and II clinical studies have shown that for CML patients in the chronic and accelerated phases with resistance or intolerance to various TKIs, with or without T315I mutations, there are significant hematological and molecular responses and survival benefits. Olverembatinib can also inhibit many other kinases related to tumors. In vitro studies have shown that olverembatinib downregulates MCL-1 expression and acts synergistically with BCL-2 inhibitors to induce apoptosis of AML cells.
Preclinical studies have shown that venetoclax has a synergistic effect with TKIs. It upregulates apoptosis-inducing proteins, downregulates anti-apoptotic protein MCL1, inhibits the anti-apoptotic activity of BCL-XL, induces apoptosis of Ph+ cells, overcomes TKI resistance, and eliminates CML leukemia stem cells.
Read more
A large amount of evidence indicates that DNA hypermethylation plays an important role in the progression of CML, and abnormal DNA methylation is associated with progression to the accelerated and blast crisis phases and resistance to TKIs.Domestic scholars have reported successful cases of combined treatment with TKI, venetoclax, and demethylating agent azacitidine for CML patients with lymphoid blast crisis.
Therefore, we designed this study to explore the efficacy and safety of olverembatinib, venetoclax, and azacitidine in the treatment of CML patients in the blast crisis phase.
Read the detailed description
In patients with chronic myeloid leukemia (CML) in the blase crsis phase who are aged≥15 years, olverembatinib combined with venetoclax and azacitidine was applied for induction and consolidation therapy. After remission, allogeneic stem cell transplantation was performed or olverembatinib combined with venetoclax and azacitidine was continued for consolidation and maintenance therapy. The maximum tolerated dose of the combined chemotherapy of olverembatinib, venetoclax and azacitidine was determined, and the efficacy and safety of the combined chemotherapy were evaluated.
Primary Endpoints Phase I: Determine the maximum tolerated dose of the combined chemotherapy of olverembatinib, venetoclax and azacitidine.
Phase II: Determine the complete hematological response rate (CHR) after 2 courses of treatment.
- Conditions
- CML,Blast Phase
- Being tested
- Olverembatinib, Venetoclax, Azacitidine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlverembatinibDrug
induction therapy：40mg,QOD；
consolidation maintenance therapy: If patients with CMR are reduced to 30mg.
VenetoclaxDrug
induction therapy：leverl 0: 100mg d-2; 200mg d-1; 400mg d1-14
leverl -1: 100mg d-2; 200mg d-1; 400mg d1-7
leverl 1: 100mg d-2; 200mg d-1; 400mg d1-21
consolidation maintenance therapy: 400mg d1-7
AzacitidineDrug
induction therapy：75mg/m2/d, d1-7
consolidation maintenance therapy: 75mg/m2/d, d1-7
| Study group | Role | What they receive |
|---|---|---|
| Olverembatinib Combined With Venetoclax and Azacitidine | Other | Not described Receives: Drug: Olverembatinib; Drug: Venetoclax; Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the maximum tolerated dose of combination with olverembatinib, venetoclax and azacitidine
The standard "3+3" method is used to determine the maximum tolerated dose. There are 3 dose groups.
Measured: six weeks from day 1 of each course
Determine complete hematological response rate (CHR) after 2 courses
CHR is one of the evaluation criteria of treatment.
Measured: six weeks after day 1 of 2nd courses of the treatment
Secondary outcomes (7)
Partial Cytogenetic Response（PCyR）
PCyR is an important clinical indicator for determining whether patients with CML are responding well to the treatment they are receiving.
Measured: up to 2 years
Complete Cytogenetic Response（CCyR）
It is another important indicator used to assess the response to treatment in patients with chronic myeloid leukemia (CML). In the CCyR state, the patient's bone marrow cells no longer detect any abnormal cells carrying the Philadelphia chromosome.
Measured: up to 2 years
Major Molecular Response（MMR）
When the test results show that the expression level of the BCR-ABL gene is reduced below a specific threshold, the patient is considered to have achieved MMR.
Measured: up to 2 years
Deep Molecular Response（DMR）
It is an advanced indicator to assess the response of patients with chronic myeloid leukemia (CML) to treatment. DMR indicates that the expression level of the BCR-ABL fusion gene has been reduced to a very low level, which usually indicates that the patient's disease is in a very stable controlled state with a low risk of recurrence.
Measured: up to 2 years
overall survival (OS)
Used to evaluate all patients who enter clinical trials. From the date of entry into the trial until the date of patient death (including any cause) or last survival follow-up.
Measured: up to 2 years after the date of the last enrolled participants
Relapse-free survival (RFS)
Defined only for patients achieving CRc; measured from the date of achievement of remission until the date of hematologic relapse or death from any cause; patients not known to have relapsed or died at last follow-up are censored on the date they were last known to be alive
Measured: up to 2 years after the date of the last enrolled participants
Therapeutic toxicity
This is a safety indicator and focuses on treatment-related toxicity.
Measured: up to 2 years after the date of the last enrolled participants
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jan 2025
- Study start26 Jan 2025
- Primary completion1 Dec 2026 (estimated)
- Study completion1 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CML,Blast PhaseStudies of the same condition, open and under way.
- More trials run by Institute of Hematology & Blood Diseases Hospital, ChinaThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06757855
- Sponsor's protocol ID
- IIT2024090
- Status last verified
- Dec 2024
- First submitted
- 27 Dec 2024
- Last updated
- 30 May 2025
- Results posted
- No
- Data monitoring committee
- No
- 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 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Single-arm I/II Clinical Study of Olverembatinib Combined With Venetoclax and Azacitidine in in Blast Phase Ph Chromosome- Chronic Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT06757855
- Acronym / sponsor ID
- IIT2024090
- Conditions
- CML,Blast Phase
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 29 participants (estimated)
- Lead sponsor
- Institute of Hematology & Blood Diseases Hospital, ChinaUniversity, hospital or other
- Study start
- 26 Jan 2025 (actual)
- Primary completion
- 1 Dec 2026 (estimated)
- Study completion
- 1 Dec 2028 (estimated)
- First posted
- 3 Jan 2025 (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.
Even in the TKI era, the outcoms of patients with blast phase is still poor.The response rate to conventional intensive chemotherapy is only 12.5% and the 5-year survival rate is 0 for patients with myeloid blast crsis. The response rate of TKI monotherapy is about 50% and the response rate is further improved when combined TKI and chemotherapy for patients with lymphoid blast crsis. The induction remission rate of chemotherapy alone for patients with Ph-positive acute lymphoblastic leukemia is 50-60%, and the remission rate increases to more than 95% when combined with TKI. Therefore, the application of TKI for patients in the blast crisis phase is of great significance. Olverembatinib is the only third-generation TKI drug approved in the Chinese mainland at present. Preclinical research data show that olverembatinib has a significant inhibitory effect on wild-type and mutant ABL resistant to the first and second-generation TKIs, as well as some complex mutations resistant to ponatinib. Phase I and II clinical studies have shown that for CML patients in the chronic and accelerated phases with resistance or intolerance to various TKIs, with or without T315I mutations, there are significant hematological and molecular responses and survival benefits. Olverembatinib can also inhibit many other kinases related to tumors. In vitro studies have shown that olverembatinib downregulates MCL-1 expression and acts synergistically with BCL-2 inhibitors to induce apoptosis of AML cells.
Preclinical studies have shown that venetoclax has a synergistic effect with TKIs. It upregulates apoptosis-inducing proteins, downregulates anti-apoptotic protein MCL1, inhibits the anti-apoptotic activity of BCL-XL, induces apoptosis of Ph+ cells, overcomes TKI resistance, and eliminates CML leukemia stem cells.
A large amount of evidence indicates that DNA hypermethylation plays an important role in the progression of CML, and abnormal DNA methylation is associated with progression to the accelerated and blast crisis phases and resistance to TKIs.Domestic scholars have reported successful cases of combined treatment with TKI, venetoclax, and demethylating agent azacitidine for CML patients with lymphoid blast crisis.
Therefore, we designed this study to explore the efficacy and safety of olverembatinib, venetoclax, and azacitidine in the treatment of CML patients in the blast crisis phase.
Detailed description
In patients with chronic myeloid leukemia (CML) in the blase crsis phase who are aged≥15 years, olverembatinib combined with venetoclax and azacitidine was applied for induction and consolidation therapy. After remission, allogeneic stem cell transplantation was performed or olverembatinib combined with venetoclax and azacitidine was continued for consolidation and maintenance therapy. The maximum tolerated dose of the combined chemotherapy of olverembatinib, venetoclax and azacitidine was determined, and the efficacy and safety of the combined chemotherapy were evaluated.
Primary Endpoints Phase I: Determine the maximum tolerated dose of the combined chemotherapy of olverembatinib, venetoclax and azacitidine.
Phase II: Determine the complete hematological response rate (CHR) after 2 courses of treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Olverembatinib Combined With Venetoclax and Azacitidine | Other | Drug: Olverembatinib, Drug: Venetoclax, Drug: Azacitidine |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Patients with t(9;22)(q34;q11)/BCR::ABL1 positive blast-phase CML who are aged 15 years or older, whether initially in the blast phase or progressing from the chronic phase, with no gender restriction.
- Blast phase criteria: Conforming to the 2022 WHO criteria for CML Blast phase: bone marrow or peripheral blood blast cells ≥ 20%; for diagnosis of acute lymphoblastic transformation, if the immature lymphoblasts (determined by immunophenotype) ≥ 5% according to the ICC 2022 criteria; blast cell aggregation in bone marrow or extramedullary tissues.
- ECOG performance status score ≤ 2.
- Major organ function assessment criteria: Total bilirubin < 1.5×upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5×ULN; serum creatinine < 2×ULN; myocardial enzymes < 2×ULN; serum amylase ≤ 1.5×ULN; left ventricular ejection fraction (LEF) within the normal range on echocardiography.
- Men and women of reproductive potential agree and adopt effective contraceptive measures.
Key exclusion criteria (12 listed)
- Before group entry, other systemic anti-cancer treatments for acute transformation were received (excluding single-agent TKI, hormone, or hydroxyurea for reducing tumor burden before group entry, and single-agent olverembatinib ≤ 14 days)
- Myocardial infarction occurred within 12 months before enrollment in this study; other clinically significant cardiac diseases (such as unstable angina, congestive heart failure, uncontrollable hypertension, uncontrollable arrhythmia, etc.)
- Uncontrolled active severe infection
- Known positive serum HIV
- Acute pancreatitis occurred within 1 year before study screening, or a history of chronic pancreatitis
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 |
|---|---|---|
| Olverembatinibinduction therapy：40mg,QOD； consolidation maintenance therapy: If patients with CMR are reduced to 30mg. | Drug | Olverembatinib Combined With Venetoclax and Azacitidine |
| Venetoclaxinduction therapy：leverl 0: 100mg d-2; 200mg d-1; 400mg d1-14 leverl -1: 100mg d-2; 200mg d-1; 400mg d1-7 leverl 1: 100mg d-2; 200mg d-1; 400mg d1-21 consolidation maintenance therapy: 400mg d1-7 | Drug | Olverembatinib Combined With Venetoclax and Azacitidine |
| Azacitidineinduction therapy：75mg/m2/d, d1-7 consolidation maintenance therapy: 75mg/m2/d, d1-7 | Drug | Olverembatinib Combined With Venetoclax and Azacitidine |
Primary outcome
To determine the maximum tolerated dose of combination with olverembatinib, venetoclax and azacitidine
Time frame: six weeks from day 1 of each course
The standard "3+3" method is used to determine the maximum tolerated dose. There are 3 dose groups.
Determine complete hematological response rate (CHR) after 2 courses
Time frame: six weeks after day 1 of 2nd courses of the treatment
CHR is one of the evaluation criteria of treatment.
7 secondary outcomes
Partial Cytogenetic Response（PCyR）
Time frame: up to 2 years
Complete Cytogenetic Response（CCyR）
Time frame: up to 2 years
Major Molecular Response（MMR）
Time frame: up to 2 years
Deep Molecular Response（DMR）
Time frame: up to 2 years
overall survival (OS)
Time frame: up to 2 years after the date of the last enrolled participants
Relapse-free survival (RFS)
Time frame: up to 2 years after the date of the last enrolled participants
Therapeutic toxicity
Time frame: up to 2 years after the date of the last enrolled participants
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2025.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Olverembatinib, Venetoclax and Azacitidine in people with CML,Blast Phase, run by Institute of Hematology & Blood Diseases Hospital, China 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 12 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: looking for participants now, as of the sponsor's last update on 30 May 2025. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hui Wei, MD (13132507161, weihui@ihcams.ac.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the maximum tolerated dose of combination with olverembatinib, venetoclax and azacitidine (time frame: six weeks from day 1 of each course). The study lists 2 primary outcomes in all. 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 May 2025.