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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
Sponsored by
Institute of Hematology & Blood Diseases Hospital, China
About
Eligibility
Locations
Arms
Outcomes
Full info

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:

  1. Male or female patients aged 14 years or older
  2. 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
  3. Eastern Cooperative Oncology Group (ECOG) Performance status 0-2
  4. 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%;
  5. Subject has provided written informed consent prior to any screening procedure

Exclusion Criteria:

  1. Lymphoid blast crisis of chronic myelocytic leukemia (CML)
  2. Previous or ongoing systemic anti-ALL therapy (including but not restricted to TKI and/or radiotherapy, except for appropriate pre-treatment)
  3. Clinical manifestations of CNS or extramedullary involvement with ALL
  4. 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.)
  5. Uncontrolled active serious infections that could, in the investigator's opinion, potentially interfere with the completion of treatment
  6. Known HIV seropositivity
  7. History of acute pancreatitis within 1 year of study screening or history of chronic pancreatitis
  8. Uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL)
  9. Female patients who are pregnant or breast feeding
  10. Poorly controlled diabetes, defined as glycosylated hemoglobin (HbA1c) values of >7.5%. Patients with preexisting, well-controlled diabetes are not excluded
  11. 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

First Posted
October 21, 2022
Last Updated
October 3, 2023
Sponsor
Institute of Hematology & Blood Diseases Hospital, China
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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
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

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
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.
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
No
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
Email
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
Email
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

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

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