Clinical trial NCT05579132: A Clinical Study of MK-1045 (CN201) in People With Precursor B-cell Acute Lymphoblastic Leukemia (MK-1045-002)
Official title: An Open-label, Multi-center Phase Ib/II Study of MK-1045 (CN201) in Subjects With Precursor B-cell Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Acute Lymphoblastic Leukemia
Lead sponsor: MSD R&D (China) Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-10-13
Enrollment: 203
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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

Primary outcomes:
measure: Dose Escalation Phase: Number of Participants who Experience at Least One Adverse Event (AE)
timeFrame: Up to approximately 24 months
measure: Dose Escalation Phase: Number of Participants who Discontinue Study Treatment Due to an AE
timeFrame: Up to approximately 21 months
measure: Dose Escalation Phase: Number of Participants Who Experience a Dose-limiting Toxicity (DLT)
timeFrame: Up to 28 days
measure: Dose Escalation Phase: Maximum Tolerated Dose (MTD) of MK-1045
timeFrame: Up to approximately 21 months
measure: Phase II: Complete Remission (CR) Rate
timeFrame: Up to approximately 10 weeks
Secondary outcomes:
measure: Dose Escalation Phase: Area Under the Concentration-Time Curve from Time 0 to Last (AUC0-Last) of MK-1045
timeFrame: At designated time points up to approximately 24 weeks
measure: Dose Escalation Phase: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of MK-1045
timeFrame: At designated time points up to approximately 24 weeks
measure: Dose Escalation Phase: Area Under the Concentration-time Curve From Time 0 to 168 hours (AUC0-168)
timeFrame: At designated time points up to approximately 24 weeks
measure: Dose Escalation Phase: AUC From Time 0 to 168 Hours at Steady State (AUC0-tau)
timeFrame: At designated time points up to 24 weeks
measure: Dose Escalation Phase: Maximum Serum Drug Concentration (Cmax) of MK-1045
timeFrame: At designated time points up to approximately 32 weeks
measure: Dose Escalation Phase: Time to Maximum Serum Drug Concentration of MK-1045
timeFrame: At designated time points up to approximately 24 weeks
measure: Dose Escalation Phase: Concentration at End of Dosing Interval (Ctrough) of MK-1045
timeFrame: At designated time points up to approximately 12 months
measure: Dose Escalation Phase: Apparent Terminal Half Life (t1/2)
timeFrame: At designated time points up to approximately 24 weeks
measure: Dose Escalation Phase: Apparent Clearance (CL) of MK-1045
timeFrame: At designated time points up to approximately 24 weeks
measure: Dose Escalation Phase: Apparent Volume of Distribution (Vz) of MK-1045
timeFrame: At designated time points up to approximately 24 weeks
measure: Dose Escalation Phase: Apparent Volume of Distribution at Theoretical Steady State (Vss) of MK-1045
timeFrame: At designated time points up to approximately 24 weeks
measure: Dose Escalation Phase: Mean Residence Time (MRT) of MK-1045
timeFrame: At designated time points up to approximately 24 weeks
measure: Dose Escalation Phase: Peripheral B Cell Depletion of MK-1045
timeFrame: Baseline and at designated time points up to approximately 12 months
measure: Dose Escalation Phase: Peripheral Circulating T Cell Activation of of MK-1045
timeFrame: Baseline and at designated time points up to approximately 12 months
measure: Dose Escalation Phase: Percentage of Participants with Antidrug Antibodies (ADA) to MK-1045
timeFrame: At designated time points up to approximately 12 months
measure: Dose Escalation Phase: Rate of Complete Remission (CR) and Complete Remission with Partial Hematologic Recovery (CRh)
timeFrame: Up to approximately 10 weeks
measure: Dose Escalation Phase: Rate of CR, CRh, and Complete Response with Incomplete Hematologic Recovery (CRi)
timeFrame: Up to approximately 10 weeks
measure: Dose Escalation Phase: Rate of Minimum Residual Disease (MRD)-negative Complete Remission
timeFrame: Up to approximately 12 months
measure: Dose Escalation Phase: Rate of Red Blood Cell and Platelet Transfusion Independence (TI)
timeFrame: Up to approximately 24 months
measure: Phase II: Number of Participants Who Experience at Least 1 AE
timeFrame: Up to approximately 24 months
measure: Phase II: Number of Participants who Discontinue Study Treatment Due to an AE
timeFrame: Up to approximately 24 months
measure: Phase II: Maximum Serum Drug Concentration (Cmax) of MK-1045
timeFrame: At designated time points up to 4 weeks
measure: Phase II: Concentration at End of Dosing Interval (Ctrough) of MK-1045
timeFrame: At designated time points up to 4 weeks
measure: Phase II: Peripheral B Cell Depletion of MK-1045
timeFrame: Baseline and at designated time points up to 4 weeks
measure: Phase II: Peripheral Circulating T Cell Activation of of MK-1045
timeFrame: Baseline and at designated time points up to 4 weeks
measure: Phase II: Concentration of Peripheral Cytokines
timeFrame: Baseline and at designated time points up to 4 weeks
measure: Phase II: Percentage of participants with Antidrug Antibodies (ADA) to MK-1045
timeFrame: At designated time points up to 4 weeks
measure: Phase II: Rate of CR and CRh
timeFrame: Up to approximately 10 weeks
measure: Phase II: Rate of CR/CRh/CRi
timeFrame: Up to approximately 10 weeks
measure: Phase II: Rate of Minimum Residual Disease (MRD)-negative Complete Remission
timeFrame: Up to approximately 24 months
measure: Phase II: Rate of Red Blood Cell and Platelet TI
timeFrame: Up to approximately 24 months
measure: Phase II: Proportion of Participants Undergoing Hematopoietic Stem Cell Transplantation (HSCT)
timeFrame: Up to approximately 24 months
measure: Phase II: Duration of CR
timeFrame: Up to approximately 24 months
measure: Phase II: Duration of CR/CRh
timeFrame: Up to approximately 24 months
measure: Phase II: Duration of CR/CRh/CRi
timeFrame: Up to approximately 24 months
measure: Phase II: Relapse-Free Survival (RFS)
timeFrame: Up to approximately 24 months
measure: Phase II: Overall Survival (OS)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Third Military Medical University ( Site 0008)
state: Chongqing
city: Guangzhou
country: China
facility: Southern Medical University Nanfang Hospital ( Site 0004)
state: Guangdong
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University ( Site 0003)
state: Hebei
city: Harbin
country: China
facility: The First Hospital of Harbin ( Site 0005)
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital-hematology department ( Site 0002)
state: Henan
city: Wuhan
country: China
facility: Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology ( Site 0010)
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital affiliated to Tongji Medical College of HUST ( Site 0006)
state: Hubei
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University ( Site 0007)
state: Jiangsu
city: Chengdu
country: China
facility: West China Second University Hospital, Sichuan University ( Site 0011)
state: Sichuan
city: Tianjin
country: China
facility: Hematology Hospital of Chinese Academy of Medical Sciences ( Site 0001)
state: Tianjin
city: Hangzhou
country: China
facility: The Children's Hospital of Zhejiang University School of Medicine ( Site 0009)
state: Zhejiang
Study officials:
affiliation: Institute of Hematology & Blood Diseases Hospital, China
name: Jianxiang Wang, Dr.
role: PRINCIPAL_INVESTIGATOR
References: