Ph-Positive Acute Lymphoblastic Leukemia
Conditions
Keywords
Ph-positive ALL, Venetoclax+Azacitidine+Orebatinib
Brief summary
The purpose of this study is to evaluate the efficacy and safety of Venetoclax, Azacitidine Plus Orebatinib in newly diagnosed Philadelphia chromosome-positive Acute Lymphoblastic Leukemia.
Detailed description
This is a phase Ⅱ, single-arm, open Label, multicenter clinical study in newly diagnosed Ph-positive acute lymphoblastic leukemia patients. The patients will receive venetoclax, azacitidine and orebatinib regimen in the induction treatment. The patients who respond to induction treatment will undergo consolidation treatment, and an optional allogeneic hematopoietic stem cell transplantation and post-transplantation maintenance treatment with induction therapy according to patient's wishes.
Interventions
DRUGVenetoclax
100mg d1, 200mg d2, 400mg d2-21, oral (Adjusted according to the plasma concentration of venetoclax on day 4)，every 28 days for a treatment cycle.
DRUGAzacitidine
75mg/m2 qd, d1-d7, subcutaneous injection, every 28 days for a treatment cycle.
DRUGOrebatinib
20mg qod, d4-d21, oral, every 28 days for a treatment cycle.
Sponsors
The First Affiliated Hospital of Soochow University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Newly diagnosed Ph-positive ALL without the history of chemotherapy or target therapy. 2. Age ≥18. 3. Eastern Cooperative Oncology Group (ECOG) score: 0-3. 4. Total serum bilirubin ≤ 2 x upper limit of normal (ULN), alanine aminotransferase (ALT) ≤ 1.5 x ULN, aspartate aminotransferase (AST) ≤ 1.5 x ULN. 5. Creatinine clearance ≥ 30 mL/min. 6. Serum lipase ≤ 1.5 x ULN, amylase =\< 1.5 x ULN. 7. Provide informed consent.
Exclusion criteria
1. Patients with another malignant disease. 2. Patients with uncontrolled active infection. 3. Patients with left ventricular ejection fraction \< 0.5 by echocardiography or grade III/IV cardiovascular dysfunction according to the New York Heart Association Classification. 4. Patients with HIV infection, active tuberculosis infection, or active hepatitis B or hepatitis C infection. 5. Patients with uncontrolled active bleeding. 6. Patients who has participated or participating in other clinical trials related to this disease. 7. Patients with history of previous chemotherapy or target therapy (except for oral hydroxyurea and/or leukopheresis for lowering white blood cell counts). 8. Pregnant and lactating women; patients of childbearing potential should be willing to practice methods of contraception throughout the study period. 9. Patients with other commodities that the investigators considered not suitable for the enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| complete molecular remission（CMR） | End of cycle 1 and 2 (each cycle is 28 days) | Proportion of patients achieving CMR at the end of 1 or 2 cycles |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CRi | End of cycle 1 and 2 (each cycle is 28 days) | CR with incomplete hematologic recovery (CRi) was defined as \<5% bone marrow blasts, either ANC\<1×10\^9/L or platelets \< 100×10\^9/L, transfusion independence but with persistence of cytopenia. |
| MRD-negative CR | End of cycle 1 and 2 (each cycle is 28 days) | Minimal residual disease (MRD)-negative CR was defined as a leukemic cell count below the sensitivity threshold of 1×10-4 (0.01%) bone marrow mononuclear cells (MNCs) by multiparameter flow cytometry. |
| CCyR | End of cycle 1 and 2 (each cycle is 28 days) | Complete cytogenetic response (CCyR) was defined as lack of Ph in ≥ 20 bone marrow metaphases. |
| CR | End of cycle 1 and 2 (each cycle is 28 days) | Complete remission (CR) was defined as \< 5% bone marrow blasts in an aspirate with spicules and independent of transfusions. |
| Number of adverse events | End of cycle 1 and 2 (each cycle is 28 days) | Adverse events are evaluated with CTCAE V5.0 |
| RFS | 1 year | Relapse-free survival (RFS) was the duration from the day of CR to leukemia relapse, death, or last follow-up |
| OS | 1 year | Overall survival (OS) was the time from enrollment to death for any reason. |
| MMR | End of cycle 1 and 2 (each cycle is 28 days) | Major molecular response (MMR) was defined as a BCR-ABL/ABL transcript ratio of 0.1% (international scale). |
Countries
China
Contacts
Primary ContactXiaowen Tang, Ph.D
Backup ContactDepei Wu, Ph.D
Outcome results
None listed