Asciminib & Standard-of-Care Integration in Maintenance Therapy for POST Allogeneic Stem Cell Transplant (Allo-HSCT) of Patient With Ph+ B-ALL or Blastic Transformed CML

Официальное название

Efficacy and Safety of Adding Asciminib to the Standard-of-care for Post Allogenic Hematopoietic Stem-cell Transplant (HSCT) Maintenance in Philadelphia Chromosome-positive B-cell Acute Lymphoblastic Leukemia (Ph+ B-ALL) or Blastic Transformed CML (Myeloid or Lymphoid) (CML-BP)

Обзор

The goal of this clinical trial is to learn if Asciminib, a first in class allosteric inhibitor, as a add-on maintenance therapy can provides benefits and further prevents relapse in post allogenic hematopoietic stem-cell transplant (HSCT) of patients with Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (Ph+ B-ALL) or blastic transformed Chronic Myeloid Leukemia (CML-BP). The main questions it aims to answer are: Would Ascminib add-on maintenance therapyimprove Morphological relapse-free survival rate? Would Ascminib add-on maintenance therapy improve Molecular relapse-free survival and Overall survival ? Any toxicity or intolerable events during Ascminib add-on maintenance therapy? Researchers will compare Study arm (Ascminib plus tyrosine-kinase inhibitors \[TKIs\]) and Control arm (TKIs only) to see if Ascminib add-on maintenance therapy would provide better relapse-free survival (RFS) with optimal tolerability. Participants will * Enrolled and Randomized into either Study arm or Control arm * Take Ascminib plus selected TKI or selected TKI only according to schedule * Visit the clinic once every 2-4 weeks for checkups and tests * Record and Report any adverse event and graft-versus-host-disease (GvHD) development

Подробное описание

Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (Ph+ B-ALL) or blastic transformed Chronic Myeloid Leukemia (myeloid or lymphoid) (CML-BP) represent a group of high-risk disease. The outcome has improved since the introduction of tyrosine kinase inhibitors (TKIs). However, a significant proportion of patients still relapse despite undergoing allogeneic (allo-) hematopoietic stem cell transplant (HSCT) and post-transplant maintenance with TKIs. Moreover, many patients may not be able to tolerate the standard recommended dose of TKIs due to cytopenia especially during the early phase after transplant.

Asciminib is a first in class allosteric inhibitor that works by a mechanism totally different from the current TKIs in market. Its safety and efficacy have been studied in previous studies. We therefore postulate that combination of standard ATP-competitive TKIs (our current standard of care) and asciminib as post allo-HSCT maintenance can more effectively reduce risk of relapse post-transplant without increased toxicities.

This is a two-arm, parallel group, single-center, prospective, open-label, randomized clinical study to investigate the efficacy and safety of adding asciminib to the standard-of-care for post allogenic HSCT maintenance in patients with Ph+ B-ALL or CML-BP to prevent post-HSCT relapse.

Subjects in study group will receive Asciminib plus standard of care (SOC) while those in control group will receive standard of care. Eligible subjects will be randomized into study group and control group in a 2:1 ratio.

The subjects in study group commence study drug (Asciminib) for post-transplant maintenance at 80 mg QD (in combination with nilotinib or dasatinib) or 60 mg QD (in combination with imatinib) after stable count recovery (i.e. absolute neutrophile count \[ANC\] ≥ 1.0 × 109/L, granulocyte colony-stimulating factor (G-CSF) independent and platelet ≥ 50 × 109/L, transfusion independent). SOC TKI will be added from 5th week onwards after.

Вмешательства

• Препарат Asciminib add-on
  Asciminib 80mg QD (in combination with Nilotinib or Dasatinib) or Asciminib 60mg QD (in combination with Imatinib)
• Препарат Imatinib
  Imatinib 300mg QD (Ramp-up from 100mg QD for first 4-weeks, 200mg QD for following 4-weeks then 300mg QD for subsequent weeks), Maximum 2-years treatment
• Препарат Dasatinib
  Dasatinib 50mg QD (Ramp-up from 20mg QD for first 4-weeks, 40mg QD for following 4-weeks then 50mg QD for subsequent weeks), Maximum 2-years treatment
• Препарат Nilotinib
  Nilotinib 200mg BID (Ramp-up from 200mg QD for first 4-weeks then 200mg BID for subsequent weeks), Maximum 2-years treatment

Первичные конечные точки

• Morphological relapse-free survival (M-RFS) [Срок оценки: From date of allogeneic HSCT until the date of first documented morphological relapse or death from any cause, whichever occurs earlier, up to 12 years.]

Вторичные конечные точки (7)

• Molecular relapse-free survival (m-RFS) [Срок оценки: From date of randomization until the date of first documented molecular relapse or death from any cause, whichever occurs earlier, up to 12 years.]
• Cumulative incidence of grade II-IV acute Graft versus Host Disease (acute GvHD) [Срок оценки: Within 100 day after allogeneic Hematopoietic Stem Cell Transplantation (HSCT)]
• Cumulative incidence of chronic Graft versus Host Disease (chronic GvHD) [Срок оценки: From enrollment through study completion, an average of 2 years]
• Treatment toxicities and Adverse Events (AEs) [Срок оценки: From randomization through treatment completion, an average of 2 years]
• Event-free survival (EFS) [Срок оценки: From date of allogeneic HSCT until the date of first documented morphological relapse, molecular relapse, onset of acute of chronic GvHD or death from any cause, whichever occurs earlier, up to 12 years.]
• Overall survival (OS) [Срок оценки: From date of allogeneic HSCT until the date of death from any cause or trial completion, whichever occurs earlier, up to 12 years.]
• 2-year morphological relapse-free survival rate (2-year M-RFS rate) [Срок оценки: From date of allogeneic HSCT until the date of first documented morphological relapse, molecular relapse, or death from any cause, whichever occurs earlier, up to 2 years.]

Критерии участия

Критерии включения

• The subject (or the subject's legally acceptable representative, if applicable) must be capable of giving written informed consent and, prior to the commencement of any study-specific procedure, must sign an informed consent form (ICF) indicating the consent on the subject's voluntary participation in the study and compliance with the requirements and restrictions listed on the ICF.
• Age ≥ 18 years
• Patients with Ph+ B-ALL or CML-BP, who had undergone allogeneic HSCT
• Patients must have received TKI therapy in induction/consolidation therapy
• Absolute neutrophil count ≥ 1.0 × 109/L
• Platelet count ≥ 50 × 109/L

Критерии исключения

• Patients with known atypical transcript that cannot be measured by available polymerase chain reaction (PCR) methods.
• Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2
• Uncontrolled hypertension
• Corrected QT interval (QTc) > 460 milliseconds for women or > 450 milliseconds for men
• Amylase and lipase values > 3 × upper limit of normal
• Patients refused standard TKI maintenance post-HSCT
• Unable to comply with study requirements
• Patients taking ponatinib as choice of TKI
• Patients with documented T315I mutation

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Гонконг · 1 центр

• The University of Hong Kong — Гонконг

Идентификаторы

NCT: NCT07493408 · ASCPT-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗