Efficacy and Safety of Low-dose Chemotherapy Plus Immuno-targeted Drugs in Newly Diagnosed Adult Ph- B-ALL

Официальное название

Efficacy and Safety of Low-dose Chemotherapy Combined With Immuno-targeted Drugs in Newly Diagnosed Adult Patients With Ph-negative B-cell Acute Lymphocytic Leukemia: A Prospective, Single-arm Clinical Study

Обзор

In the treatment of Ph-negative (Ph-) B-cell acute lymphoblastic leukemia (B-ALL) among adult patients, therapeutic outcomes remain suboptimal despite advances in chemotherapy and immunotherapy. A subset of adults with Ph- B-ALL have comorbidities or physiological limitations that preclude the safe administration of intensive regimens. In recent years, tumor immunotherapy has demonstrated promising safety and efficacy profiles in refractory or relapsed Ph- B-ALL across a wide spectrum of adult ages. These findings suggest that broader application of immunotherapy may represent a critical strategy to improve survival in this population. In this study, we propose a regimen that combines immuno-targeted agents with low-intensity chemotherapy for newly diagnosed adult patients with Ph- B-ALL. Our primary objective is to increase the rate of measurable residual disease (MRD)-negative complete remission (CR) following induction therapy, reduce the risk of relapse, and ultimately enhance overall survival.

Подробное описание

In this open-label, single-arm, Phase II study, prospective clinical trial, a total of 53 Ph-negative (Ph-) B-cell acute lymphoblastic leukemia (B-ALL) patients will be enrolled. The primary endpoint is measurable residual disease (MRD)-negative complete remission (CR) rate after induction therapy.

The first cycle of induction therapy is administered with Inotuzumab ozogamicin (INO), Venetoclax (VEN), and a combination of low-dose chemotherapy. The second cycle of induction therapy is Blinatumomab (Blino) plus VEN regimen. Alternatively, the first cycle of induction therapy is a combination of VEN and low-dose chemotherapy, and the second cycle of induction therapy is methotrexate (MTX) plus cytarabine (Ara-C) plus VEN regimen. Subsequent consolidation and maintenance therapy consist of low-dose chemotherapy, Blino, and VEN. Patients can receive chimeric antigen receptor T-Cell (CAR-T) Immunotherapy or allogeneic hematopoietic stem cell transplantation (HSCT) or receive autologous HSCT whenever possible during their first CR. Otherwise, they will finish the consolidation chemotherapy. Study patients are scheduled for follow-up for at least 5 years after the end of maintenance therapy.

The purpose of current study is to determine the efficacy and safety of low-dose chemotherapy combined with immuno-targeted drugs in newly diagnosed adult patients with Ph- B-ALL.

Вмешательства

• Препарат Vincristine
  Anti-tumor alkaloids
• Препарат Cyclophosphamide
  Alkylating agent
• Препарат Dexamethasone
  Glucocorticoids
• Препарат Venetoclax
  Selective inhibitor of B-cell lymphoma 2 (Bcl-2)
• Препарат Inotuzumab ozogamicin
  A humanized monoclonal antibody-drug conjugate targeting CD22
• Препарат Blinatumomab
  Bi-specific anti-CD19/CD3 antibodies
• Препарат 6-mercaptopurine
  Cell cycle-specific antitumor drug
• Препарат Methotrexate
  Antifolate antineoplastic drug
• Препарат Cytarabine
  Pyrimidine antimetabolites
• Препарат Prednisone
  Glucocorticoids

Первичные конечные точки

• MRD-negative complete remission rate measured by flow cytometry. [Срок оценки: After induction (4 week)]

Вторичные конечные точки (5)

• Complete remission (CR) rate [Срок оценки: an expected average of 3 months]
• Overall survival (OS) [Срок оценки: Up to 5 years post-registration]
• Relapse free survival (RFS) [Срок оценки: Up to 5 years post-registration]
• Disease-free Survival (DFS) [Срок оценки: Up to 5 years post-registration]
• Mortality [Срок оценки: Day 30 and Day 60 of induction therapy initiation]

Критерии участия

Критерии включения

• Newly diagnosed Ph-negative B-cell acute lymphoblastic leukemia according to World Health Organization (WHO) 2016 criteria
• CD22 positive tumor cells
• ≥18 years of age
• Estimated survival ≥3 months
• Consent and effective contraception for men and women of childbearing potential
• Understanding and signing of informed consent forms and agreement to comply with study requirements.

Критерии исключения

• Burkitt lymphoma/leukemia
• acute leukemias of ambiguous lineage
• pregnant women
• severe uncontrolled active infection
• previous history of chronic liver disease (e.g. cirrhosis) or venous occlusive liver disease (VOD) or sinus obstruction syndrome (SOS)
• History of clinically significant ventricular arrhythmia, syncope of unknown origin (not vasovagal) or sinoatrial block or higher degree atrioventricular (AV) block Chronic bradycardia state (unless permanent pacemaker implanted)
• New or chronic hepatitis B or C infection (positive for hepatitis B surface antigen and anti-hepatitis C antibody, respectively) or known HIV seropositivity. HIV testing may need to be performed according to local regulations or practices
• Psychiatric disorders likely to prevent the subject from completing treatment or informed consent
• Other conditions considered unsuitable for the study by the investigator.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Institute of Hematology & Blood Diseases Hospital — Тяньцзинь

Публикации

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• Davis KL, Yao CC, Zimmerman JAO, Rau RE. Immunotherapy in B-Cell Acute Lymphoblastic Leukemia. J Natl Compr Canc Netw. 2025 Dec;23(12):e257067. doi: 10.6004/jnccn.2025.7067. PMID 41671463

Идентификаторы

NCT: NCT06387121 · IIT2023060

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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