A Clinical Study of MK-1045 (CN201) in People With Precursor B-cell Acute Lymphoblastic Leukemia (MK-1045-002)

Официальное название

An Open-label, Multi-center Phase Ib/II Study of MK-1045 (CN201) in Subjects With Precursor B-cell Acute Lymphoblastic Leukemia

Обзор

Researchers are looking for new ways to treat people with a type of blood cancer called precursor B-cell Acute Lymphoblastic Leukemia (B-ALL) that is relapsed- the cancer has come back after treatment, or refractory - the current treatment has stopped working to slow or stop cancer growth. This study will have two parts. In the first part (dose escalation phase) the goal is to learn about the safety of a study treatment, MK-1045, and to find the best dose level of MK-1045 that is tolerated and may work to treat B-ALL. In the second part (Phase II) researchers want to learn how well MK-1045 works to treat B-ALL.

Вмешательства

• Препарат MK-1045
  MK-1045 is administered by IV infusion once a week (QW), 4 weeks per treatment cycle, starting with 2 cycles of induction treatment. After a 2-week treatment-free interval, responders to induction treatment receive 3 cycles of consolidation therapy, and up to 7 cycles of maintenance treatment or until intolerable toxicity, disease progression, withdrawal of informed consent, loss to follow-up, receipt of other antitumor therapy, or death, whichever occurs first.

Первичные конечные точки

• Dose Escalation Phase: Number of Participants who Experience at Least One Adverse Event (AE) [Срок оценки: Up to approximately 24 months]
• Dose Escalation Phase: Number of Participants who Discontinue Study Treatment Due to an AE [Срок оценки: Up to approximately 21 months]
• Dose Escalation Phase: Number of Participants Who Experience a Dose-limiting Toxicity (DLT) [Срок оценки: Up to 28 days]
• Dose Escalation Phase: Maximum Tolerated Dose (MTD) of MK-1045 [Срок оценки: Up to approximately 21 months]
• Phase II: Complete Remission (CR) Rate [Срок оценки: Up to approximately 10 weeks]

Вторичные конечные точки (12)

• Dose Escalation Phase: Area Under the Concentration-Time Curve from Time 0 to Last (AUC0-Last) of MK-1045 [Срок оценки: At designated time points up to approximately 24 weeks]
• Dose Escalation Phase: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of MK-1045 [Срок оценки: At designated time points up to approximately 24 weeks]
• Dose Escalation Phase: Area Under the Concentration-time Curve From Time 0 to 168 hours (AUC0-168) [Срок оценки: At designated time points up to approximately 24 weeks]
• Dose Escalation Phase: AUC From Time 0 to 168 Hours at Steady State (AUC0-tau) [Срок оценки: At designated time points up to 24 weeks]
• Dose Escalation Phase: Maximum Serum Drug Concentration (Cmax) of MK-1045 [Срок оценки: At designated time points up to approximately 32 weeks]
• Dose Escalation Phase: Time to Maximum Serum Drug Concentration of MK-1045 [Срок оценки: At designated time points up to approximately 24 weeks]
• Dose Escalation Phase: Concentration at End of Dosing Interval (Ctrough) of MK-1045 [Срок оценки: At designated time points up to approximately 12 months]
• Dose Escalation Phase: Apparent Terminal Half Life (t1/2) [Срок оценки: At designated time points up to approximately 24 weeks]
• Dose Escalation Phase: Apparent Clearance (CL) of MK-1045 [Срок оценки: At designated time points up to approximately 24 weeks]
• Dose Escalation Phase: Apparent Volume of Distribution (Vz) of MK-1045 [Срок оценки: At designated time points up to approximately 24 weeks]
• Dose Escalation Phase: Apparent Volume of Distribution at Theoretical Steady State (Vss) of MK-1045 [Срок оценки: At designated time points up to approximately 24 weeks]
• Dose Escalation Phase: Mean Residence Time (MRT) of MK-1045 [Срок оценки: At designated time points up to approximately 24 weeks]

Критерии участия

The main inclusion criteria include but are not limited to:

• Adult participants must be age 18 or older
• Pediatric participants must be at least 2 years old and less than 18 years old.
• Diagnosis of precursor B-cell acute lymphoblastic leukemia (B-ALL) and have more than 5% blasts in the bone marrow by morphological assessment
• Participants with Ph-negative B-ALL with any of the following refractory/relapse criteria:

• Failure to achieve complete remission after initial induction therapy;
• Failure to achieve complete remission after salvage treatment;
• Relapse with first remission duration ≤12 months
• Second or later relapse
• Relapse after allogeneic HSCT
• Participants with Ph-positive B-ALL who have received 2 (or more) tyrosine kinase inhibitors (TKIs) and meet the refractory/relapse criteria above or, those with the T315I mutation

The main exclusion criteria include but are not limited to:

• History of Burkitt's leukemia.
• Received anti-CD19 therapy within 3 months prior to entering the study
• Received allogeneic HSCT within 12 weeks prior to entering the study
• Received prior treatment with chimeric antigen receptor T cell (CAR-T) within 3 months prior to entering the study
• History or presence of clinically relevant central nervous system (CNS) pathology
• History of clinically symptomatic metastases to the central nervous system or meninges, or other evidence of uncontrolled metastases to the CNS or meninges
• History of immunodeficiency, including history of any positive test result for human immunodeficiency virus (HIV) antibody.
• History of serious cardiovascular and cerebrovascular disease
• Has active autoimmune diseases that may relapse

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 · 11 центров

• The Second Affiliated Hospital of Third Military Medical University ( Site 0008) — Чунцин
• Southern Medical University Nanfang Hospital ( Site 0004) — Гуанчжоу
• The Second Hospital of Hebei Medical University ( Site 0003) — Shijiazhuang
• The First Hospital of Harbin ( Site 0005) — Харбин
• Henan Cancer Hospital-hematology department ( Site 0002) — Чжэнчжоу
• Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and — Ухань
• Tongji Hospital affiliated to Tongji Medical College of HUST ( Site 0006) — Ухань
• The Affiliated Hospital of Xuzhou Medical University ( Site 0007) — Xuzhou
• … и ещё 3 центра

Идентификаторы

NCT: NCT05579132 · 1045-002 · MK-1045-002 · CN201-103

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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