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Olverembatinib Combined With Reduced-Intensity Chemotherapy and Venetoclax for de Novo Ph+ ALL

Primary Purpose

Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Olverembatinib

Venetoclax

prednisone

Vincristine

About this trial

This is an interventional treatment trial for Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Eligibility Criteria

14 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female patients aged 14 years or older
Newly diagnosed Philadelphia chromosome positive(either t(9;22) and/or BCR-ABL positive and/ or FISH positive) acute lymphoblastic leukemia; Patients will be diagnosed according to morphologic,immunologic, cytogenetic and molecular(MICM) criteria, including bone marrow morphology, immunophenotype, cytogenetic and molecular genetic (BCR/ABL gene, qualitative and quantitative analysis) examination
Eastern Cooperative Oncology Group (ECOG) Performance status 0-2
Adequate end organ function as defined by: Total bilirubin ≤ 1.5 x upper limit of normal（ULN）; serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) ≤ 2.5 x ULN or ≤5 x ULN if leukemic involvement of the liver is present; Creatinine ≤ 1.5 x ULN; Serum amylase and lipase ≤ 1.5 x ULN; Alkaline phosphatase ≤ 2.5 x ULN unless considered tumor related; normal electrolytes: Potassium ≥ LLN; Magnesium ≥ LLN; Phosphorus ≥ LLN; Cardiac color Doppler ultrasound ejection fraction ≥ 45%;
Subject has provided written informed consent prior to any screening procedure

Exclusion Criteria:

Lymphoid blast crisis of chronic myelocytic leukemia (CML)
Previous or ongoing systemic anti-ALL therapy (including but not restricted to TKI and/or radiotherapy, except for appropriate pre-treatment)
Clinical manifestations of CNS or extramedullary involvement with ALL
Patients with a history of myocardial infarction within 12 months or clinically significant cardiac disorders disease (e.g., unstable angina, congestive heart failure, uncontrollable hypertension, uncontrollable arrhythmia, etc.)
Uncontrolled active serious infections that could, in the investigator's opinion, potentially interfere with the completion of treatment
Known HIV seropositivity
History of acute pancreatitis within 1 year of study screening or history of chronic pancreatitis
Uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL)
Female patients who are pregnant or breast feeding
Poorly controlled diabetes, defined as glycosylated hemoglobin (HbA1c) values of >7.5%. Patients with preexisting, well-controlled diabetes are not excluded
Any serious psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment

Sites / Locations

Institute of Hematology & Blood Diseases HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Olverembatinib Combined With Reduced-Intensity Chemotherapy and Venetoclax

Arm Description

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.

Outcomes

Primary Outcome Measures

CMR rate

Complete molecular remission rate (CMR rate) at 3 months of treatment (90 days)

Secondary Outcome Measures

Overall survival(OS)

From the date of registration to the date of death resulting from any cause

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

The rate of adverse events

complete remission (CR) rate

The duration of CR

The duration of molecular CR

Full Information

NCT ID

NCT05594784

First Posted

October 21, 2022

Last Updated

October 3, 2023

Sponsor

Institute of Hematology & Blood Diseases Hospital, China

1. Study Identification

Unique Protocol Identification Number

NCT05594784

Brief Title

Olverembatinib Combined With Reduced-Intensity Chemotherapy and Venetoclax for de Novo Ph+ ALL

Official Title

Olverembatinib Combined With Reduced-Intensity Chemotherapy and Venetoclax for Newly Diagnosed Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia: A Prospective, Single-arm, Single-center Clinical Trial

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

October 8, 2022 (Actual)

Primary Completion Date

October 25, 2024 (Anticipated)

Study Completion Date

March 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Institute of Hematology & Blood Diseases Hospital, China

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Olverembatinib Combined With Reduced-Intensity Chemotherapy and Venetoclax

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Olverembatinib

Intervention Description

a third-generation TKI

Intervention Type

Drug

Intervention Name(s)

Venetoclax

Intervention Description

a selective inhibitor of B-cell lymphoma 2 (Bcl-2)

Intervention Type

Drug

Intervention Name(s)

prednisone

Intervention Description

Glucocorticoids

Intervention Type

Drug

Intervention Name(s)

Vincristine

Intervention Description

Anti-tumor alkaloids

Primary Outcome Measure Information:

Title

CMR rate

Description

Complete molecular remission rate (CMR rate) at 3 months of treatment (90 days)

Time Frame

At 3 months of treatment (90 days)

Secondary Outcome Measure Information:

Title

Overall survival(OS)

Description

From the date of registration to the date of death resulting from any cause

Time Frame

up to 60 months

Title

Relapse free survival

Description

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

Time Frame

up to 60 months

Title

The rate of adverse events

Time Frame

an expected average of 24 months

Title

complete remission (CR) rate

Time Frame

an expected average of 3 months

Title

The duration of CR

Time Frame

up to 60 months

Title

The duration of molecular CR

Time Frame

up to 60 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

14 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female patients aged 14 years or older Newly diagnosed Philadelphia chromosome positive(either t(9;22) and/or BCR-ABL positive and/ or FISH positive) acute lymphoblastic leukemia; Patients will be diagnosed according to morphologic,immunologic, cytogenetic and molecular(MICM) criteria, including bone marrow morphology, immunophenotype, cytogenetic and molecular genetic (BCR/ABL gene, qualitative and quantitative analysis) examination Eastern Cooperative Oncology Group (ECOG) Performance status 0-2 Adequate end organ function as defined by: Total bilirubin ≤ 1.5 x upper limit of normal（ULN）; serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) ≤ 2.5 x ULN or ≤5 x ULN if leukemic involvement of the liver is present; Creatinine ≤ 1.5 x ULN; Serum amylase and lipase ≤ 1.5 x ULN; Alkaline phosphatase ≤ 2.5 x ULN unless considered tumor related; normal electrolytes: Potassium ≥ LLN; Magnesium ≥ LLN; Phosphorus ≥ LLN; Cardiac color Doppler ultrasound ejection fraction ≥ 45%; Subject has provided written informed consent prior to any screening procedure Exclusion Criteria: Lymphoid blast crisis of chronic myelocytic leukemia (CML) Previous or ongoing systemic anti-ALL therapy (including but not restricted to TKI and/or radiotherapy, except for appropriate pre-treatment) Clinical manifestations of CNS or extramedullary involvement with ALL Patients with a history of myocardial infarction within 12 months or clinically significant cardiac disorders disease (e.g., unstable angina, congestive heart failure, uncontrollable hypertension, uncontrollable arrhythmia, etc.) Uncontrolled active serious infections that could, in the investigator's opinion, potentially interfere with the completion of treatment Known HIV seropositivity History of acute pancreatitis within 1 year of study screening or history of chronic pancreatitis Uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL) Female patients who are pregnant or breast feeding Poorly controlled diabetes, defined as glycosylated hemoglobin (HbA1c) values of >7.5%. Patients with preexisting, well-controlled diabetes are not excluded Any serious psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jianxiang Wang, Dr

Phone

86-22-23909120

wangjx@ihcams.ac.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jianxiang Wang, Dr

Organizational Affiliation

Institute of Hematology & Blood Diseases Hospital, China

Official's Role

Principal Investigator

Facility Information:

Facility Name

Institute of Hematology & Blood Diseases Hospital

City

Tianjin

ZIP/Postal Code

300020

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jianxiang Wang, Dr.

Phone

86-22-23909120

wangjx@medmail.com.cn

First Name & Middle Initial & Last Name & Degree

Jianxiang Wang, Dr.

First Name & Middle Initial & Last Name & Degree

Ying Wang, Dr.

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Learn more about this trial

Olverembatinib Combined With Reduced-Intensity Chemotherapy and Venetoclax for de Novo Ph+ ALL

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