Case-Only: Decitabine and HQP1351-based Chemotherapy Regimen for the Treatment Advanced CML

Sponsor

Nanfang Hospital of Southern Medical University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05376852

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase II trial studies how well the combination of based decitabine and olverembatinib（HQP1351)chemotherapy work for the treatment of blast phase or accelerated phase chronic myelogenous leukemia. Drugs used in chemotherapy such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. HQP1351 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving decitabine and ponatinib based chemotherapy may help to control blast phase or accelerated phase chronic myelogenous leukemia.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloid Leukemia in Myeloid Blast Crisis Chronic Myeloid Leukaemia Transformation Chronic Myeloid Leukemia - Accelerated Phase Chronic Myeloid Leukemia in Lymphoid Blast Crisis (Diagnosis)	Combination Product: based decitabine and olverembatinib（HQP1351)chemotherapy	Phase 2

Detailed Description

Accelerated Phase CML treated with decitabine 20mg/m2 d1-5 intravenously (IV) over 60 minutes on days 1-5 and olverembatinib（HQP1351) 40mg qod every 28 days.After completion of HQP1351 lead-in, patients will receive HQP1351 PO daily on days 1-28 of subsequent cycles.

Acute Myeloid Leukemia post Blast Phase CML:treated with decitabine 20mg/m2 d1-5 intravenously (IV) over 60 minutes on days 1-5 and HQP1351 40mg qod every 28 days,plus HHT2mg/M2 d6-8+Ara-c 15mg/m2 q12h d6-12,or together with Venetoclax d1-14 Acute lymphoblastic Leukemia and Acute mixed leukemia post Blast Phase CML:treated with decitabine 20mg/m2 d1-5 intravenously (IV) over 60 minutes on days 1-5 and HQP1351 40mg qod every 28 days,plus VDP（2 weeks)+/ Venetoclax d6-20

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Decitabine and HQP1351-based Chemotherapy Regimen for the Treatment Advanced Chronic Myeloid Leukemia

Actual Study Start Date :

Dec 1, 2021

Anticipated Primary Completion Date :

Dec 31, 2024

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: treatment group Based decitabine and olverembatinib（HQP1351)chemotherapy	Combination Product: based decitabine and olverembatinib（HQP1351)chemotherapy AP-CML treated with decitabine 20mg/m2 d1-5 intravenously (IV) over 60 minutes on days 1-5 and HQP1351 40mg qod every 28 days.After completion of HQP1351 lead-in, patients will receive HQP1351 PO qod on days 1-28 of subsequent cycles. AML post Blast Phase CML:treated with decitabine 20mg/m2 d1-5 IV on days 1-5 and HQP1351 40mg qod every 28 days,plus HHT2mg/M2 d6-8+Ara-c 15mg/m2 q12h d6-12,or together with Venetoclax d1-14 ALL and Acute mixed leukemia post Blast Phase CML:treated with decitabine 20mg/m2 d1-5 over 60 minutes on days 1-5 and HQP1351 40mg qod every 28 days,plus VDP（2 weeks)+/ Venetoclax d6-20

Arm

Intervention/Treatment

Experimental: treatment group

Based decitabine and olverembatinib（HQP1351)chemotherapy

Combination Product: based decitabine and olverembatinib（HQP1351)chemotherapy

AP-CML treated with decitabine 20mg/m2 d1-5 intravenously (IV) over 60 minutes on days 1-5 and HQP1351 40mg qod every 28 days.After completion of HQP1351 lead-in, patients will receive HQP1351 PO qod on days 1-28 of subsequent cycles. AML post Blast Phase CML:treated with decitabine 20mg/m2 d1-5 IV on days 1-5 and HQP1351 40mg qod every 28 days,plus HHT2mg/M2 d6-8+Ara-c 15mg/m2 q12h d6-12,or together with Venetoclax d1-14 ALL and Acute mixed leukemia post Blast Phase CML:treated with decitabine 20mg/m2 d1-5 over 60 minutes on days 1-5 and HQP1351 40mg qod every 28 days,plus VDP（2 weeks)+/ Venetoclax d6-20

Outcome Measures

Primary Outcome Measures

Overall response rate [End of cycle 2 (each cycle is 28 days)]
Defined as the proportion of patients achieving complete remission (CR) + CR with incomplete count recovery (CRi) occurring at the end of 2 cycles of treatment. Will be estimated along with the 95% credible interval. Patients who drop out of the study before completing 2 cycles and have been treated will be censored for the primary endpoint analysis.

Secondary Outcome Measures

Rate of minimal residual disease negativity [Up to 4 years]
Will be estimated along with the 95% credible interval

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

myeloid accelerated phase (AP)-chronic myelogenous leukemia (CML) or blast phase (BP)-CML (either t[9;22] and/or BCR-ABL1 positive by fluorescent in situ hybridization or polymerase chain reaction). Both untreated and relapsed/refractory patients are eligible
Performance status =< 3 (Eastern Cooperative Oncology Group [ECOG] scale)
Total serum bilirubin =< 2 x upper limit of normal (ULN), unless due to Gilbert's syndrome, hemolysis or the underlying leukemia approved by the principal investigator (PI) Alanine aminotransferase (ALT) =< 1.5 x ULN, unless due to the underlying leukemia approved by the PI Aspartate aminotransferase (AST) =< 1.5 x ULN unless due to the underlying leukemia approved by the PI Creatinine clearance >= 30 mL/min Serum lipase =< 1.5 x ULN Amylase =< 1.5 x ULN Ability to swallow Signed informed consent

Exclusion Criteria:

Active serious infection not controlled by oral or intravenous antibiotics (e.g. persistent fever or lack of improvement despite antimicrobial treatment) History of acute pancreatitis within 6 months of study or history of chronic pancreatitis Uncontrolled hypertriglyceridemia (triglycerides > 450 mg/dL) Active secondary malignancy that in the investigator's opinion will shorten survival to less than 1 year Active grade III-V cardiac failure as defined by the New York Heart Association criteria

Clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:

Myocardial infarction (MI), stroke, revascularization, unstable angina or transient ischemic attack within 6 months Left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards prior to enrollment Diagnosed or suspected congenital long QT syndrome Clinically significant atrial or ventricular arrhythmias (such as uncontrolled, clinically significant atrial fibrillation, ventricular tachycardia, ventricular fibrillation, or torsades de pointes) as determined by the treating physician Prolonged corrected QT (QTc) interval on pre-entry electrocardiogram (> 480 msec) unless corrected after electrolyte replacement History of venous thromboembolism including deep venous thrombosis or pulmonary embolism within the past 3 months, excluding line-associated deep venous thrombosis (DVT) of the upper extremity Uncontrolled hypertension (diastolic blood pressure > 100 mmHg; systolic > 150 mmHg)