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The introduction of TKIs has greatly improved the prognosis of Ph+ ALL patients. The third-generation TKI ponatinib in combination with chemotherapy has demonstrated superior efficacy to first- and second-generation TKIs. However, unfortunately, ponatinib is not available in mainland China. Olverembatinib is the only third-generation TKI drug currently approved in mainland China. Venetoclax is an oral selective inhibitor of Bcl-2, and small exploratory clinical studies have demonstrated that venetoclax in combination with ponatinib showed high rates of CR as well as molecular response in relapsed/refractory Ph+ ALL. This study will explore the safety and efficacy of olverembatinib in combination with reduced-intensity chemotherapy and venetoclax in patients with newly diagnosed Ph+ ALL.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Olverembatinib Combined With Reduced-Intensity Chemotherapy and Venetoclax | Experimental | For Induction cycle, olverembatinib will be given orally 40mg every other day. Patients with CMR, olverembatinib will be reduced to 30 mg every other day. Induction and consolidation cycles combined with a certain period of venetoclax. Reduced-intensity chemotherapy regimens consist mainly of vincristine and prednisone. Patients can receive allogeneic hematopoietic stem cell transplantation (HSCT),or patients who keep BCR/ABL negative can receive autologous HSCT whenever possible during their first CR. Otherwise, they will finish the consolidation chemotherapy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Olverembatinib | Drug | a third-generation TKI |
|
| Measure | Description | Time Frame |
|---|---|---|
| CMR rate | Complete molecular remission rate (CMR rate) at 3 months of treatment (90 days) | At 3 months of treatment (90 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival(OS) | From the date of registration to the date of death resulting from any cause | up to 60 months |
| Relapse free survival | From the date of complete remission(CR) until the date of documented relapse or death due to any cause or the last follow-up day |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jianxiang Wang, Dr | Institute of Hematology & Blood Diseases Hospital, China | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institute of Hematology & Blood Diseases Hospital | Tianjin | 300020 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40588568 | Derived | Gong X, Liu W, Liu Y, Fang Q, Gu R, Liu K, Lin D, Zhou C, Zhang G, Gong B, Wei S, Li Y, Li S, Wang Y, Hu Y, Qiu S, Liu B, Wang Y, Mi Y, Wei H, Wang J. Olverembatinib combined with venetoclax and reduced-intensity chemotherapy for adult newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a single-center, single-arm, phase 2 trial. Leukemia. 2025 Aug;39(8):1838-1847. doi: 10.1038/s41375-025-02674-8. Epub 2025 Jun 30. |
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| Venetoclax | Drug | a selective inhibitor of B-cell lymphoma 2 (Bcl-2) |
|
| prednisone | Drug | Glucocorticoids |
|
| Vincristine | Drug | Anti-tumor alkaloids |
|
| up to 60 months |
| The rate of adverse events | an expected average of 24 months |
| complete remission (CR) rate | an expected average of 3 months |
| The duration of CR | up to 60 months |
| The duration of molecular CR | up to 60 months |
| ID | Term |
|---|---|
| C579813 | olverembatinib |
| C579720 | venetoclax |
| D011241 | Prednisone |
| D014750 | Vincristine |
| ID | Term |
|---|---|
| D011244 | Pregnadienediols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D014748 | Vinca Alkaloids |
| D046948 | Secologanin Tryptamine Alkaloids |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D054836 | Indolizidines |
| D007212 | Indolizines |
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