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

Primary Purpose

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Vincristine
Daunorubicin
Cyclophosphamide
Pegaspargase
Prednisone
Cytarabine
6-mercaptopurine
Dexamethasone
Methotrexate
Venetoclax
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 Precursor Cell Lymphoblastic Leukemia-Lymphoma focused on measuring Philadelphia Chromosome-Negative, Acute Lymphoblastic Leukemia, Adolescent and Adult, Pediatric-inspired Regimen, Venetoclax

Eligibility Criteria

14 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Institute of Hematology & Blood Diseases HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pediatric-inspired Regimen Combined With Venetoclax

Arm Description

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.

Outcomes

Primary Outcome Measures

MRD-negative complete remission rate measured by flow cytometry

Secondary Outcome Measures

Complete remission (CR) rate
Overall survival (OS)
From the date of registration to the date of death resulting from any cause
Relapse free survival (RFS)
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
Disease-free Survival (DFS)
From CR1 to relapse, death from any cause or last follow-up
The rate of adverse events

Full Information

First Posted
December 13, 2022
Last Updated
March 1, 2023
Sponsor
Institute of Hematology & Blood Diseases Hospital, China
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1. Study Identification

Unique Protocol Identification Number
NCT05660473
Brief Title
Pediatric-inspired Regimen Combined With Venetoclax for Adolescent and Adult Patients With de Novo Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia
Official Title
Pediatric-inspired Regimen Combined With Venetoclax for Adolescent and Adult Patients With de Novo Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 31, 2022 (Actual)
Primary Completion Date
December 15, 2024 (Anticipated)
Study Completion Date
December 30, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Keywords
Philadelphia Chromosome-Negative, Acute Lymphoblastic Leukemia, Adolescent and Adult, Pediatric-inspired Regimen, Venetoclax

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Pediatric-inspired Regimen Combined With Venetoclax
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Vincristine
Intervention Description
Anti-tumor alkaloids
Intervention Type
Drug
Intervention Name(s)
Daunorubicin
Intervention Description
Anthracycline
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Alkylating agent
Intervention Type
Drug
Intervention Name(s)
Pegaspargase
Intervention Description
Polyethylene glycol (PEG) conjugated to L-asparaginase
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Glucocorticoids
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Intervention Description
Pyrimidine antimetabolites
Intervention Type
Drug
Intervention Name(s)
6-mercaptopurine
Intervention Description
Cell cycle-specific antitumor drug
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Glucocorticoids
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
Antifolate antineoplastic drug
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Intervention Description
Selective inhibitor of B-cell lymphoma 2 (Bcl-2)
Primary Outcome Measure Information:
Title
MRD-negative complete remission rate measured by flow cytometry
Time Frame
After induction (4 week)
Secondary Outcome Measure Information:
Title
Complete remission (CR) rate
Time Frame
After 2 cycles of chemotherapy, an expected average of 3 months
Title
Overall survival (OS)
Description
From the date of registration to the date of death resulting from any cause
Time Frame
Up to 5 years post-registration
Title
Relapse free survival (RFS)
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 5 years post-registration
Title
Disease-free Survival (DFS)
Description
From CR1 to relapse, death from any cause or last follow-up
Time Frame
Up to 5 years post-registration
Title
The rate of adverse events
Time Frame
An expected average of 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
14 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
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
No

Learn more about this trial

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

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