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

Sponsor
Institute of Hematology & Blood Diseases Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT05594784
Collaborator
(none)
30
1
1
28.7
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Study Details

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
30 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 :
Oct 8, 2022
Anticipated Primary Completion Date :
Oct 25, 2024
Anticipated Study Completion Date :
Mar 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 [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) [up to 60 months]

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

  2. Relapse free survival [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 [an expected average of 24 months]

  4. complete remission (CR) rate [an expected average of 3 months]

  5. The duration of CR [up to 60 months]

  6. The duration of molecular CR [up to 60 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:
14 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

  1. Any serious psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment

Contacts and Locations

Locations

Site City State Country Postal Code
1 Institute of Hematology & Blood Diseases Hospital Tianjin China 300020

Sponsors and Collaborators

  • Institute of Hematology & Blood Diseases Hospital

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
wang, jianxiang, Principal Investigator, Institute of Hematology & Blood Diseases Hospital
ClinicalTrials.gov Identifier:
NCT05594784
Other Study ID Numbers:
  • IIT2022040-EC-1
First Posted:
Oct 26, 2022
Last Update Posted:
Oct 26, 2022
Last Verified:
Sep 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Undecided
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:

Study Results

No Results Posted as of Oct 26, 2022