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

NCT06554626 | Recruiting Phase 2 DMC

• 1 other identifier: IIT20240070C
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Precursor B-Cell Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (1)

• Event free survival(EFS)

  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;

  up to 2 years

Secondary Outcomes (3)

• Complete remission with or without incomplete PB cell recovery(CR/CRi) rate

  at the end of Cycle 1（each cycle is 28days）

• Overall survival (OS)

  up to 5 years

• Minimal residual disease (MRD)

  At the end of Cycle 1（each cycle is 28 days）

Other Outcomes (1)

• Minimal residual disease (MRD)

  At the end of Cycle 2（each cycle is 28 days）

Study Arms (1)

Treatment arm

EXPERIMENTAL

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.

Drug: Dexamethasone; Drug: Blinatumomab; Drug: Venetoclax; Drug: Inotuzumab ozogamicin; Drug: Methotrexate; Drug: Pegaspargase; Drug: Cytarabine

Interventions

Dexamethasone DRUG

Glucocorticoids

Treatment arm

Blinatumomab DRUG

Bi-specific anti CD19/CD3 antibody

Also known as: Blina

Treatment arm

Venetoclax DRUG

BCL-2 inhibotor

Also known as: Ven

Treatment arm

Inotuzumab ozogamicin DRUG

a humanized monoclonal antibody-drug conjugate targeting CD22

Also known as: INO

Treatment arm

Methotrexate DRUG

antifolate antineoplastic drug

Also known as: MTX

Treatment arm

Pegaspargase DRUG

antitumor drug

Also known as: PEG

Treatment arm

Cytarabine DRUG

Pyrimidine, antimetabolites

Also known as: Ara-C

Treatment arm

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead

Study Sites (1)

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310003, China

RECRUITING

Related Publications (6)

• Geyer MB, Hsu M, Devlin SM, Tallman MS, Douer D, Park JH. Overall survival among older US adults with ALL remains low despite modest improvement since 1980: SEER analysis. Blood. 2017 Mar 30;129(13):1878-1881. doi: 10.1182/blood-2016-11-749507. Epub 2017 Jan 25. No abstract available.

  PMID: 28122741 BACKGROUND

• 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.

  PMID: 28249141 BACKGROUND

• 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.

  PMID: 29358182 BACKGROUND

• 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.

  PMID: 38491815 BACKGROUND

• 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.

  PMID: 27292104 BACKGROUND

• 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.

  PMID: 37187201 BACKGROUND

MeSH Terms

Conditions

Precursor B-Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Dexamethasone; blinatumomab; venetoclax; Inotuzumab Ozogamicin; Methotrexate; pegaspargase; Cytarabine

Condition Hierarchy (Ancestors)

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Jie Jin, M.D.

CONTACT

+8657187236896; jiej0503@163.com

Chenying Li, M.D.

CONTACT

+8657187236896; lcy890823@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2024
• First Posted: August 15, 2024
• Study Start: August 15, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: August 15, 2024

Record last verified: 2024-08

Locations

CN (1)