Clinical trial NCT06554626: Blinatumomab Plus Venetoclax Sequenced With Inotuzumab Ozogamicin in Treating B-ALL
Official title: The Regimen of Blinatumomab and Venetoclax Sequenced With Inotuzumab Ozogamicin in Treating Precursor B Cell Acute Lymphoblastic Leukemia: A Phase II, Single Arm and Multicenter Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Precursor B-Cell Lymphoblastic Leukemia
Lead sponsor: First Affiliated Hospital of Zhejiang University
Sponsor class: OTHER
First posted: 2024-08-15
Enrollment: 20
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Event free survival(EFS)
timeFrame: up to 2 years
Secondary outcomes:
measure: Complete remission with or without incomplete PB cell recovery(CR/CRi) rate
timeFrame: at the end of Cycle 1（each cycle is 28days）
measure: Overall survival (OS)
timeFrame: up to 5 years
measure: Minimal residual disease (MRD)
timeFrame: At the end of Cycle 1（each cycle is 28 days）
Other outcomes:
measure: Minimal residual disease (MRD)
timeFrame: At the end of Cycle 2（each cycle is 28 days）
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
References:
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citation: Kantarjian HM, DeAngelo DJ, Stelljes M, Martinelli G, Liedtke M, Stock W, Gokbuget N, O'Brien S, Wang K, Wang T, Paccagnella ML, Sleight B, Vandendries E, Advani AS. Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia. N Engl J Med. 2016 Aug 25;375(8):740-53. doi: 10.1056/NEJMoa1509277. Epub 2016 Jun 12.
citation: Jabbour E, Short NJ, Senapati J, Jain N, Huang X, Daver N, DiNardo CD, Pemmaraju N, Wierda W, Garcia-Manero G, Montalban Bravo G, Sasaki K, Kadia TM, Khoury J, Wang SA, Haddad FG, Jacob J, Garris R, Ravandi F, Kantarjian HM. Mini-hyper-CVD plus inotuzumab ozogamicin, with or without blinatumomab, in the subgroup of older patients with newly diagnosed Philadelphia chromosome-negative B-cell acute lymphocytic leukaemia: long-term results of an open-label phase 2 trial. Lancet Haematol. 2023 Jun;10(6):e433-e444. doi: 10.1016/S2352-3026(23)00073-X. Epub 2023 May 12.