Pediatric-inspired Regimen Combined With Venetoclax for Adolescent and Adult Patients With de Novo Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia

March 1, 2023 updated by: Institute of Hematology & Blood Diseases Hospital
The pediatric-inspired regimen has greatly improved the prognosis of adult patients with with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL), but relapse remains a great challenge. Venetoclax (Ven) is an oral, selective inhibitor of B-cell lymphoma 2 (Bcl-2). Although this drug is currently used primarily for acute myeloid leukemia, in vitro as well as small cohort studies suggest a effect in acute lymphoblastic leukemia. This study proposes to combine pediatric-inspired regimen with venetoclax for the treatment of adult patients with Ph- ALL, aiming to improve the MRD-negative complete remission rate measured by flow cytometry after induction and to reduce relapse, thus further improving patients overall survival.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Tianjin, China, 300020
        • Recruiting
        • Institute of Hematology & Blood Diseases Hospital
        • Contact:
        • Principal Investigator:
          • Jianxiang Wang, Dr.
        • Sub-Investigator:
          • Ying Wang, Dr.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 60 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • De novo and primary Ph/BCR-ABL1 negative acute lymphoblastic leukemia diagnosed by the bone marrow cytomorphology, immunophenotyping, cytogenetics and molecular biology according to WHO classification
  • Age: 14 -60 years
  • Male or female
  • 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:

  • Burkitt lymphoma/leukemia
  • Acute Leukemia of Ambiguous Lineage
  • Female patients who are pregnant or breast feeding
  • Uncontrolled active serious infections that could, in the investigator's opinion, potentially interfere with the completion of treatment
  • History of pancreatitis
  • Poorly controlled diabetes, defined as glycosylated hemoglobin (HbA1c) values of >7.5%. Patients with preexisting, well-controlled diabetes are not excluded
  • History of active gastrointestinal bleeding within the last 6 months
  • History of arterial/venous thrombosis within the last 6 months
  • Known HIV seropositivity
  • Any serious psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pediatric-inspired Regimen Combined With Venetoclax
Induction therapy is administered as follows：Vincristine (VCR) 1.4 mg/m2 (maximum dose 2 mg) IV on D1,8,1,5,22; Daunorubicin (DNR) 30 mg/m2/day IV on D1-3; Cyclophosphamide (CTX) 1200 mg/m2 IV on D1,15; Pegaspargase 2500u/m2 IM on D5; Prednisone 1 mg/kg/d PO on D1-14, 0.5 mg/kg/d PO on D15-28; Venetoclax 100 mg PO on D6，200 mg on D7, 400mg on D8-14, All patients underwent bone marrow aspiration on day 14 during induction. Patients with bone marrow blasts ≥10% on day 14 of induction received 7 additional days of Venetoclax on day 15-22. Consolidation therapy is a combination of multi-drug pediatric-inspired regimen chemotherapy and Venetoclax. Maintenance therapy consisted of a monthly VMMP regimen (vincristine, mercaptopurine, methotrexate, prednisone) continuing until 3 years for male and 2.5 years for female patients.
Drug: Vincristine
Anti-tumor alkaloids
Drug: Daunorubicin
Anthracycline
Drug: Cyclophosphamide
Alkylating agent
Drug: Pegaspargase
Polyethylene glycol (PEG) conjugated to L-asparaginase
Drug: Prednisone
Glucocorticoids
Drug: Cytarabine
Pyrimidine antimetabolites
Drug: 6-mercaptopurine
Cell cycle-specific antitumor drug
Drug: Dexamethasone
Glucocorticoids
Drug: Methotrexate
Antifolate antineoplastic drug
Drug: Venetoclax
Selective inhibitor of B-cell lymphoma 2 (Bcl-2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
MRD-negative complete remission rate measured by flow cytometry
Time Frame: After induction (4 week)
After induction (4 week)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete remission (CR) rate
Time Frame: After 2 cycles of chemotherapy, an expected average of 3 months
After 2 cycles of chemotherapy, an expected average of 3 months
Overall survival (OS)
Time Frame: Up to 5 years post-registration
From the date of registration to the date of death resulting from any cause
Up to 5 years post-registration
Relapse free survival (RFS)
Time Frame: Up to 5 years post-registration
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
Up to 5 years post-registration
Disease-free Survival (DFS)
Time Frame: Up to 5 years post-registration
From CR1 to relapse, death from any cause or last follow-up
Up to 5 years post-registration
The rate of adverse events
Time Frame: An expected average of 24 months
An expected average of 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institute of Hematology & Blood Diseases Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 31, 2022

Primary Completion (Anticipated)

December 15, 2024

Study Completion (Anticipated)

December 30, 2027

Study Registration Dates

First Submitted

December 13, 2022

First Submitted That Met QC Criteria

December 13, 2022

First Posted (Actual)

December 21, 2022

Study Record Updates

Last Update Posted (Estimate)

March 3, 2023

Last Update Submitted That Met QC Criteria

March 1, 2023

Last Verified

December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IIT2022052-EC-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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