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

Zhejiang University

Status and phase

Enrolling

Phase 2

Conditions

Precursor B-Cell Lymphoblastic Leukemia

Treatments

Drug: Dexamethasone

Drug: Inotuzumab ozogamicin

Drug: Cytarabine

Drug: Venetoclax

Drug: Blinatumomab

Drug: Methotrexate

Drug: Pegaspargase

Study type

Interventional

Funder types

Other

Identifiers

NCT06554626

IIT20240070C

Details and patient eligibility

About

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.

Full 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.

Enrollment

20 estimated patients

Sex

All

Ages

40+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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.
Age ≥ 40 years;
Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2;
Expected survival time ≥ 3 months;
No organ dysfunction that would restrict the use of this protocol during the screening period;
Understand the study and sign the informed consent form.
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

Patients with known central nervous system (CNS) involvement of ALL;
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.);
Cardiac ultrasound LVEF < 45%;
History of other malignancies within the past 5 years, excluding localized thyroid cancer and in situ skin cancer;
Serum total bilirubin > 1.5 ULN (upper limit of normal); ALT or AST > 2.5 ULN; serum creatinine > 1.5 ULN;
Known HIV infection;
Conditions affecting the use of the study drug as assessed by the investigator;
Inability to understand or comply with the study protocol.

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

20 participants in 1 patient group

Treatment arm

Experimental group

Description:

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.