Blinatumomab Plus Venetoclax Sequenced With Inotuzumab Ozogamicin in Treating B-ALL

Phase 2

Recruiting

• Conditions: Precursor B-Cell Lymphoblastic Leukemia
• Interventions: Drug: Dexamethasone; Drug: Blinatumomab; Drug: Venetoclax; Drug: Inotuzumab ozogamicin; Drug: Methotrexate; Drug: Pegaspargase; Drug: Cytarabine

• Registration Number: NCT06554626
• Lead Sponsor: First Affiliated Hospital of Zhejiang University

Brief Summary

Precursor B cell acute lymphoblastic leukemia (B-ALL) is an aggressive type of leukemia, with high relapse rate and poor long term survival in adults. Traditional treatment regimens mainly include chemotherapy and hematopoietic stem cell transplantation. In the past decade, with the application of molecular targeted drugs and immunotherapy, the survival of B-ALL patients has significantly improved. In this study，we propose a treatment approach that combines Blinatumomab and Venetoclax sequenced with Inotuzumab Ozogamicin in B-ALL adults. Our study aims to answer the safety and efficacy of this treatment regimen, and further improve the survival for those participants.

Detailed Description

This is a prospective, single-arm, phase II and open-label study. A total of 20 Ph-negative B-ALL participants will be enrolled. The primary endpoint is 2-year event free survival(EFS).

The induction therapy is a combination of Blinatumomab(Blina), Venetoclax(Ven) and Dexamethasone(DXM), and would be applied for two cycles. As for consolidation, the Inotuzumab Ozogamicin(INO) would be given on cycle 3 and cycle 5. The high dose of MTX would be given on Cycle 4 and the Ven plus L-asp would ben given on Cycle 6. Subsequent maintenance therapy contains of low dose of Chemotherapy, Blina and INO.

The purpose of this study is to explore the safety and efficacy of the whole-process management of multi-drug combination regimen in the treatment of newly diagnosed Ph-negative B-ALL patients.

Study Timeline

• Status Verified: 2024-08
• Study First Submitted: 2024-08-06
• Study First Submitted QC: 2024-08-14
• Last Update Submitted: 2024-08-14
• Study Start: 2024-08-15
• Study First Posted: 2024-08-15
• Last Update Posted: 2024-08-15
• Primary Completion: 2026-08-01
• Study Completion: 2027-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Before enrollment, a diagnosis of newly diagnosed precursor B-cell acute lymphoblastic leukemia with Philadelphia chromosome-negative must be confirmed. The diagnostic criteria refer to the 2022 WHO classification.
2. Age ≥ 40 years;
3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2;
4. Expected survival time ≥ 3 months;
5. No organ dysfunction that would restrict the use of this protocol during the screening period;
6. Understand the study and sign the informed consent form.
7. Men, women of childbearing age (only postmenopausal women who have been menopausal for at least 12 months can be considered infertile), and their partners voluntarily take effective contraceptive measures deemed effective by the investigator during the treatment period and for at least 12 months after the last dose of the study drug.

Exclusion Criteria

1. Patients with known central nervous system (CNS) involvement of ALL;
2. Diseases with abnormal heart, lung, liver, kidney, or other organ functions that may limit the patient's participation in this trial (including but not limited to severe infections, uncontrolled diabetes, severe heart failure or angina, active pulmonary tuberculosis, asthma, COPD, bronchiectasis, etc.);
3. Cardiac ultrasound LVEF < 45%;
4. History of other malignancies within the past 5 years, excluding localized thyroid cancer and in situ skin cancer;
5. Serum total bilirubin > 1.5 ULN (upper limit of normal); ALT or AST > 2.5 ULN; serum creatinine > 1.5 ULN;
6. Known HIV infection;
7. Conditions affecting the use of the study drug as assessed by the investigator;
8. Inability to understand or comply with the study protocol.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment arm	Venetoclax	Induction Cycle 1 and 2: Venetoclax for 2 weeks,oral; Blinatumomab for 2weeks, iv; Dexamethasone. Consolidation Cycle 3 and 5: Inotuzumab ozogamicin, iv. Cycle 4: Methotrexate, iv. Cycle 6: Venetoclax for 2 weeks,oral; Pegaspargase, im. Complete at least 6 intrathecal injections within 6 cycles.
Treatment arm	Dexamethasone	Induction Cycle 1 and 2: Venetoclax for 2 weeks,oral; Blinatumomab for 2weeks, iv; Dexamethasone. Consolidation Cycle 3 and 5: Inotuzumab ozogamicin, iv. Cycle 4: Methotrexate, iv. Cycle 6: Venetoclax for 2 weeks,oral; Pegaspargase, im. Complete at least 6 intrathecal injections within 6 cycles.
Treatment arm	Blinatumomab	Induction Cycle 1 and 2: Venetoclax for 2 weeks,oral; Blinatumomab for 2weeks, iv; Dexamethasone. Consolidation Cycle 3 and 5: Inotuzumab ozogamicin, iv. Cycle 4: Methotrexate, iv. Cycle 6: Venetoclax for 2 weeks,oral; Pegaspargase, im. Complete at least 6 intrathecal injections within 6 cycles.
Treatment arm	Inotuzumab ozogamicin	Induction Cycle 1 and 2: Venetoclax for 2 weeks,oral; Blinatumomab for 2weeks, iv; Dexamethasone. Consolidation Cycle 3 and 5: Inotuzumab ozogamicin, iv. Cycle 4: Methotrexate, iv. Cycle 6: Venetoclax for 2 weeks,oral; Pegaspargase, im. Complete at least 6 intrathecal injections within 6 cycles.
Treatment arm	Methotrexate	Induction Cycle 1 and 2: Venetoclax for 2 weeks,oral; Blinatumomab for 2weeks, iv; Dexamethasone. Consolidation Cycle 3 and 5: Inotuzumab ozogamicin, iv. Cycle 4: Methotrexate, iv. Cycle 6: Venetoclax for 2 weeks,oral; Pegaspargase, im. Complete at least 6 intrathecal injections within 6 cycles.
Treatment arm	Pegaspargase	Induction Cycle 1 and 2: Venetoclax for 2 weeks,oral; Blinatumomab for 2weeks, iv; Dexamethasone. Consolidation Cycle 3 and 5: Inotuzumab ozogamicin, iv. Cycle 4: Methotrexate, iv. Cycle 6: Venetoclax for 2 weeks,oral; Pegaspargase, im. Complete at least 6 intrathecal injections within 6 cycles.
Treatment arm	Cytarabine	Induction Cycle 1 and 2: Venetoclax for 2 weeks,oral; Blinatumomab for 2weeks, iv; Dexamethasone. Consolidation Cycle 3 and 5: Inotuzumab ozogamicin, iv. Cycle 4: Methotrexate, iv. Cycle 6: Venetoclax for 2 weeks,oral; Pegaspargase, im. Complete at least 6 intrathecal injections within 6 cycles.

Primary Outcome Measures

Name	Time	Method
Event free survival(EFS)	up to 2 years	Defined for all patients in a trial; measured from day 1 of treatment to the date of treatment failure, hematologic relapse from CR/CRi or death from any cause, whichever occurs first;

Secondary Outcome Measures

Name	Time	Method
Complete remission with or without incomplete PB cell recovery(CR/CRi) rate	at the end of Cycle 1（each cycle is 28days）	Blast rate lower than 5% with or without peripheral blood cell recovery
Overall survival (OS)	up to 5 years	Defined for all patients in a trial; measured from day 1 of treatment to the date of death from any cause;
Minimal residual disease (MRD)	At the end of Cycle 1（each cycle is 28 days）	MRD level detected by flow cytometry which value \<0.1% is defined as negtive

Trial Locations

Locations (1)

The First Affiliated Hospital, Zhejiang University School of Medicine; 🇨🇳 Hangzhou, Zhejiang, China