A Phase 1/2 interventional study of Olverembatinib and Venetoclax in CML,Blast Phase, sponsored by Institute of Hematology & Blood Diseases Hospital, China. Recruiting at 1 site in China. Open to participants aged 15 Years and older. Per ClinicalTrials.gov, last updated 2025-05-30.
Sponsored by Institute of Hematology & Blood Diseases Hospital, China · Phase 1/2, Interventional, and Treatment
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.
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.
137 studies on the registry are indexed under Blast Crisis; 13 are open to participants now.
This study's planned enrollment of 29 is below the median of 35 across 117 interventional studies indexed under Blast Crisis.
Browse Blast Crisis studies →Institute of Hematology & Blood Diseases Hospital, China is the lead sponsor of 398 studies on the registry; 293 are open to participants now.
Counted across the registry records on this site, refreshed daily.
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.
Exclusion Criteria:
Drug: Olverembatinib · Drug: Venetoclax · Drug: Azacitidine
induction therapy：40mg,QOD； consolidation maintenance therapy: If patients with CMR are reduced to 30mg.
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
induction therapy：75mg/m2/d, d1-7 consolidation maintenance therapy: 75mg/m2/d, d1-7
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.
Time frame: 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.
Time frame: six weeks after day 1 of 2nd courses of the treatment
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: up to 2 years after the date of the last enrolled participants
Plan to share: No
No publications or documents are linked to this record.
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Institute of Hematology & Blood Diseases Hospital, China