Efficacy and Safety of Olverembatinib Plus Inotuzumab Ozogamicin as First-Line Consolidation Therapy Followed by HSCT in Ph+ ALL

Официальное название

A Study on the Efficacy and Safety of Olverembatinib Combined With Inotuzumab Ozogamicin as First-Line Consolidation Therapy Bridging to Hematopoietic Stem Cell Transplantation in Patients With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Обзор

To study the minimal residual disease (MRD) clearance rate of olverembatinib combined with inotuzumab ozogamicin as first-line consolidation chemotherapy in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) who have not achieved MRD remission after initial induction chemotherapy.

Подробное описание

In the previous study, which employed a regimen of olverembatinib combined with inotuzumab ozogamicin to clear MRD in patients with Ph⁺ ALL before bridging to transplantation, the results indicated that this combination achieved a high MRD clearance rate in patients with poor prognosis, along with a high bridging transplantation rate, significantly improving patient outcomes. In the present study, the investigators propose the use of olverembatinib combined with inotuzumab ozogamicin as first-line consolidation therapy. This approach aims to reduce the number of pre-transplant chemotherapy cycles for patients who do not achieve MRD negativity after initial induction chemotherapy, enabling them to attain deeper remission more rapidly. It is expected to provide more transplantation opportunities, including the potential for autologous hematopoietic stem cell transplantation, for this patient population.

Вмешательства

• Препарат Olverembatinib+INO
  First-Line Consolidation Chemotherapy with Olverembatinib + Inotuzumab Ozogamicin Olverembatinib: 40 mg every other day (QOD), from day 1 to day 28. Inotuzumab Ozogamicin: 1.2 mg/m² per cycle, administered as: 0.6 mg/m² on day 2 0.6 mg/m² on day 8

Первичные конечные точки

• MRD clearance [Срок оценки: one month]

Вторичные конечные точки (5)

• Overall Survival [Срок оценки: one year after HSCT]
• Relapse free survival [Срок оценки: one year after HSCT]
• Relapse rate [Срок оценки: one year after HSCT]
• Treatment related mortality [Срок оценки: one year after HSCT]
• rate of bridging to HSCT [Срок оценки: one year]

Критерии участия

Критерии включения

• (1) Clearly diagnosed acute lymphoblastic leukemia, with Philadelphia chromosome positivity or BCR-ABL fusion gene positivity; with CD22 expression on the surface of leukemia cells; failure to achieve minimal residual disease (MRD) negativity after first induction chemotherapy (BCR-ABL fusion gene level ≥ 10-⁴), where the induction regimen is standard chemotherapy combined with any tyrosine kinase inhibitor targeting BCR-ABL1.
• (2) Age greater than or equal to 18 years.
• (3) Able to provide informed consent independently.
• (4) Must have adequate organ function: renal and hepatic functions as follows: AST, ALT, and ALP less than 2 times the upper limit of normal (ULN), total bilirubin less than 1.5 times ULN; creatinine clearance greater than 50 mL/min; pancreatic function: serum amylase not exceeding 1.5 times ULN, serum lipase not exceeding 1.5 times ULN; normal cardiac function: ejection fraction (EF) > 60%, pulmonary artery systolic pressure ≤ 50 mmHg.
• (5) Negative for HIV, HBV, and HCV.
• (6) Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0-2.
• (7) Informed consent must be signed before the start of study procedures. For subjects aged 18 years and above, informed consent should be signed by the patient themselves or their immediate family members. Considering the patient's condition, if signing by the patient themselves is detrimental to treatment, the legal guardian or immediate family member may sign the informed consent.

Критерии исключения

• (1) Mixed lineage leukemia;
• (2) Involvement of the central nervous system or extramedullary infiltration;
• (3) Patients with concurrent other malignancies; or those assessed by the investigator as having concomitant diseases that severely endanger the patient's life or affect the completion of the study;
• (4) Patients with severe allergy to the components or excipients of InO (≥ Grade 3);
• (5) History of clinically significant liver diseases, such as hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS); or severe/uncontrolled liver diseases, such as cirrhosis, decompensated liver disease, acute or chronic hepatitis;
• (6) Active cardiac disease, defined as one or more of the following: history of any cardiac or vascular disease; history of uncontrolled or symptomatic angina; myocardial infarction within 6 months prior to study enrollment; history of arrhythmias requiring medication or with severe clinical symptoms; uncontrolled or symptomatic congestive heart failure (> New York Heart Association \[NYHA\] Class 2); ejection fraction below the lower limit of normal; pulmonary artery systolic pressure > 50 mmHg on echocardiography; or clinical symptoms related to pulmonary hypertension;
• (7) History of severe cardiovascular events (including myocardial infarction, unstable angina, severe arrhythmias, congestive heart failure, etc.) during previous tyrosine kinase inhibitor (TKI) treatment for chronic myeloid leukemia (CML);
• (8) Abnormal coagulation function;
• (9) Known seropositivity for HIV or active hepatitis C virus;
• (10) Patients with psychiatric disorders or other conditions that prevent compliance with study treatment and monitoring requirements;
• (11) Inability or unwillingness to sign the consent form;
• (12) Pregnant or lactating women;
• (13) Patients assessed by the investigator as ineligible due to other special circumstances.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07443488 · IIT2025119

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗