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

NCT ID: NCT06554626

Last Updated: 2024-08-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-15
• Study Completion Date: 2027-08-01

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.

Conditions

Precursor B-Cell Lymphoblastic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment arm

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.

Group Type: EXPERIMENTAL

Dexamethasone

Intervention Type: DRUG

Glucocorticoids

Blinatumomab

Intervention Type: DRUG

Bi-specific anti CD19/CD3 antibody

Venetoclax

Intervention Type: DRUG

BCL-2 inhibotor

Inotuzumab ozogamicin

Intervention Type: DRUG

a humanized monoclonal antibody-drug conjugate targeting CD22

Methotrexate

Intervention Type: DRUG

antifolate antineoplastic drug

Pegaspargase

Intervention Type: DRUG

antitumor drug

Cytarabine

Intervention Type: DRUG

Pyrimidine, antimetabolites

Interventions

Dexamethasone

Glucocorticoids

Intervention Type: DRUG

Blinatumomab

Bi-specific anti CD19/CD3 antibody

Intervention Type: DRUG

Venetoclax

BCL-2 inhibotor

Intervention Type: DRUG

Inotuzumab ozogamicin

a humanized monoclonal antibody-drug conjugate targeting CD22

Intervention Type: DRUG

Methotrexate

antifolate antineoplastic drug

Intervention Type: DRUG

Pegaspargase

antitumor drug

Intervention Type: DRUG

Cytarabine

Pyrimidine, antimetabolites

Intervention Type: DRUG

Other Intervention Names

Blina; Ven; INO; MTX; PEG; Ara-C

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.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

First Affiliated Hospital of Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jie Jin, M.D.

Role: CONTACT

jiej0503@163.com

+8657187236896

Chenying Li, M.D.

Role: CONTACT

lcy890823@126.com

+8657187236896

Facility Contacts

Jie Jin, M.D.

Role: primary

jiej0503@163.com

+86571-87236896

References

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Reference Type: BACKGROUND

PMID: 28122741 (View on PubMed)

Kantarjian H, Stein A, Gokbuget N, Fielding AK, Schuh AC, Ribera JM, Wei A, Dombret H, Foa R, Bassan R, Arslan O, Sanz MA, Bergeron J, Demirkan F, Lech-Maranda E, Rambaldi A, Thomas X, Horst HA, Bruggemann M, Klapper W, Wood BL, Fleishman A, Nagorsen D, Holland C, Zimmerman Z, Topp MS. Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia. N Engl J Med. 2017 Mar 2;376(9):836-847. doi: 10.1056/NEJMoa1609783.

Reference Type: BACKGROUND

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Gokbuget N, Dombret H, Bonifacio M, Reichle A, Graux C, Faul C, Diedrich H, Topp MS, Bruggemann M, Horst HA, Havelange V, Stieglmaier J, Wessels H, Haddad V, Benjamin JE, Zugmaier G, Nagorsen D, Bargou RC. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018 Apr 5;131(14):1522-1531. doi: 10.1182/blood-2017-08-798322. Epub 2018 Jan 22.

Reference Type: BACKGROUND

PMID: 29358182 (View on PubMed)

Lu J, Zhou H, Zhou X, Yang Y, Tong L, Miao M, Yang X, Chen S. Reduced-dose chemotherapy followed by blinatumomab in induction therapy for newly diagnosed B-cell acute lymphoblastic leukemia. Cancer Med. 2024 Mar;13(5):e7062. doi: 10.1002/cam4.7062.

Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 27292104 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 37187201 (View on PubMed)

Other Identifiers

IIT20240070C

Identifier Type: -

Identifier Source: org_study_id