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

• ClinicalTrials.gov Identifier: NCT05594784
• Recruitment Status: Recruiting
• First Posted: October 26, 2022
• Last Update Posted: October 5, 2023
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China
• Information provided by (Responsible Party): wang, jianxiang, Institute of Hematology & Blood Diseases Hospital, China

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.

Condition or disease	Intervention/treatment	Phase
Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia	Drug: Olverembatinib; Drug: Venetoclax; Drug: prednisone; Drug: Vincristine	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: October 8, 2022
• Estimated Primary Completion Date: October 25, 2024
• Estimated Study Completion Date: March 1, 2025

Arms and Interventions

Arm

Intervention/treatment

Experimental: Olverembatinib Combined With Reduced-Intensity Chemotherapy and Venetoclax; 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.

Drug: Olverembatinib; a third-generation TKI; Drug: Venetoclax; a selective inhibitor of B-cell lymphoma 2 (Bcl-2); Drug: prednisone; Glucocorticoids; Drug: Vincristine; Anti-tumor alkaloids

Outcome Measures

Primary Outcome Measures :

1. CMR rate [ Time Frame: At 3 months of treatment (90 days) ]
   Complete molecular remission rate (CMR rate) at 3 months of treatment (90 days)

Secondary Outcome Measures :

1. Overall survival(OS) [ Time Frame: up to 60 months ]
   From the date of registration to the date of death resulting from any cause
2. Relapse free survival [ Time Frame: up to 60 months ]
   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
3. The rate of adverse events [ Time Frame: an expected average of 24 months ]
4. complete remission (CR) rate [ Time Frame: an expected average of 3 months ]
5. The duration of CR [ Time Frame: up to 60 months ]
6. The duration of molecular CR [ Time Frame: up to 60 months ]

Eligibility Criteria

• Ages Eligible for Study: 14 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Jianxiang Wang, Dr; 86-22-23909120; wangjx@ihcams.ac.cn

Locations

China

Institute of Hematology & Blood Diseases Hospital; Recruiting

Tianjin, China, 300020

Contact: Jianxiang Wang, Dr. 86-22-23909120 wangjx@medmail.com.cn

Principal Investigator: Jianxiang Wang, Dr.

Sub-Investigator: Ying Wang, Dr.

Sponsors and Collaborators

Institute of Hematology & Blood Diseases Hospital, China

Investigators

• Principal Investigator: Jianxiang Wang, Dr; Institute of Hematology & Blood Diseases Hospital, China

More Information

• Responsible Party: wang, jianxiang, Principal Investigator, Institute of Hematology & Blood Diseases Hospital, China
• ClinicalTrials.gov Identifier: NCT05594784
• Other Study ID Numbers: IIT2022040-EC-1
• First Posted: October 26, 2022
• Last Update Posted: October 5, 2023
• Last Verified: October 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Philadelphia Chromosome; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Translocation, Genetic; Chromosome Aberrations; Pathologic Processes; Prednisone; Vincristine; Venetoclax; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action