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

Phase 2RecruitingNCT05579132

MSD R&D (China) Co., Ltd.203 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

203

Conditions

Acute Lymphoblastic Leukemia

Interventions

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.

Eligibility

Sex: ALLMin age: 2 Years

Medical Language ↔ Plain English

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

Locations (11)

The Second Affiliated Hospital of Third Military Medical University ( Site 0008)

Chongqing, Chongqing Municipality, China

RECRUITING

Southern Medical University Nanfang Hospital ( Site 0004)

Guangzhou, Guangdong, China

RECRUITING

The Second Hospital of Hebei Medical University ( Site 0003)

Shijiazhuang, Hebei, China

RECRUITING

The First Hospital of Harbin ( Site 0005)

Harbin, Heilongjiang, China

RECRUITING

Henan Cancer Hospital-hematology department ( Site 0002)

Zhengzhou, Henan, China

RECRUITING

Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology ( Site 0010)

Wuhan, Hubei, China

RECRUITING

Tongji Hospital affiliated to Tongji Medical College of HUST ( Site 0006)

Wuhan, Hubei, China

RECRUITING

The Affiliated Hospital of Xuzhou Medical University ( Site 0007)

Xuzhou, Jiangsu, China

ACTIVE_NOT_RECRUITING

West China Second University Hospital, Sichuan University ( Site 0011)

Chengdu, Sichuan, China

COMPLETED

Hematology Hospital of Chinese Academy of Medical Sciences ( Site 0001)

Tianjin, Tianjin Municipality, China

RECRUITING

...and 1 more locations

Outcomes

Primary Outcomes

Dose Escalation Phase: Number of Participants who Experience at Least One Adverse Event (AE)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

Time frame: Up to approximately 24 months

Dose Escalation Phase: Number of Participants who Discontinue Study Treatment Due to an AE

Time frame: Up to approximately 21 months

Dose Escalation Phase: Number of Participants Who Experience a Dose-limiting Toxicity (DLT)

A DLT is defined as any of the following toxicities and judged by the investigator to be related to the study drug: Hematologic toxic reactions: If thrombocytopenia, leukopenia, and anemia are caused by primary leukemia, they are not considered as DLTs. Non-Hematologic toxic reactions: Grade 4 non-hematologic toxicity that does not recover to ≤ Grade 2 within 14 days of best supportive therapy. Grade 3 rash, fatigue, fever, or infection will not be classified as DLT; other Grade 3 non-hematologic toxicities that do not recover to ≤ Grade 2 within 14 days of best supportive therapy is considered DLTs. Others that are considered as DLTs: Other toxicities considered clinically significant by the investigator that result in permanent drug withdrawal.

Time frame: Up to 28 days

Dose Escalation Phase: Maximum Tolerated Dose (MTD) of MK-1045

The MTD will be determined based on the incidence of DLT in each dose level. The dose level for which the DLT rate is closest to the target DLT rate (30%) will be selected as the MTD.

Time frame: Up to approximately 21 months

Phase II: Complete Remission (CR) Rate

Time frame: Up to approximately 10 weeks

Secondary Outcomes

Dose Escalation Phase: Area Under the Concentration-Time Curve from Time 0 to Last (AUC0-Last) of MK-1045

Blood samples will be collected to determine the AUC from time 0 to the last concentration that can be accurately measured of MK-1045

Time frame: 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

Blood samples will be collected to determine the AUC0-inf of MK-1045.

Time frame: 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)

Blood samples will be collected to determine the AUC from time to 168 hours after the start of infusion of MK-1045

Time frame: At designated time points up to approximately 24 weeks

Dose Escalation Phase: AUC From Time 0 to 168 Hours at Steady State (AUC0-tau)

Blood samples will be collected to determine the AUC0 -tau

Time frame: At designated time points up to 24 weeks

Dose Escalation Phase: Maximum Serum Drug Concentration (Cmax) of MK-1045

Blood samples will be collected to determine the maximum serum drug concentration, obtained directly from the measured value of the plasma concentration-time curve

Time frame: At designated time points up to approximately 32 weeks

Dose Escalation Phase: Time to Maximum Serum Drug Concentration of MK-1045

Blood samples will be collected to determine the Tmax of MK-1045

Time frame: At designated time points up to approximately 24 weeks

Dose Escalation Phase: Concentration at End of Dosing Interval (Ctrough) of MK-1045

Blood samples will be collected to determine the Ctrough of MK-1045

Dose Escalation Phase: Apparent Volume of Distribution at Theoretical Steady State (Vss) of MK-1045

Blood samples will be collected to determine the Vss of MK-1045

Time frame: At designated time points up to approximately 24 weeks

Dose Escalation Phase: Peripheral B Cell Depletion of MK-1045

B cell depletion will be determined at each timepoint by comparing absolute B cell numbers (as determined by flow cytometry) with those at baseline

Time frame: Baseline and at designated time points up to approximately 12 months

Dose Escalation Phase: Peripheral Circulating T Cell Activation of of MK-1045

Peripheral circulating T cell activation will be determined at each timepoint by comparing absolute T cell numbers and T cell activation markers with those at baseline

Time frame: Baseline and at designated time points up to approximately 12 months

Dose Escalation Phase: Percentage of Participants with Antidrug Antibodies (ADA) to MK-1045

Blood samples collected at designated timepoints will be used to determine the percentage of participants who develop detectable ADAs to MK-1045

Time frame: At designated time points up to approximately 12 months

Dose Escalation Phase: Rate of Complete Remission (CR) and Complete Remission with Partial Hematologic Recovery (CRh)

Time frame: Up to approximately 10 weeks

Dose Escalation Phase: Rate of CR, CRh, and Complete Response with Incomplete Hematologic Recovery (CRi)

Complete remission is defined as follows: \< 5% blasts in the bone marrow, no circulating lymphoblasts or extramedullary disease, and full recovery of peripheral blood counts: Platelets ≥100×10\^9/L, and absolute neutrophil count (ANC) ≥1.0×10\^9/L. CRh is defined as meeting all of the following criteria: Satisfaction of all criteria for CR except partial recovery of peripheral blood counts (platelets ≥ 50 ×10\^9/L and ANC ≥ 0.5×10\^9/L). CRi is defined as follows: \<5% blasts in the bone marrow, No circulating lymphoblasts or extramedullary disease, and platelets \<100×10\^9/L and neutrophils ≥1.0×109/L or platelets ≥100 ×109/L and neutrophils \<1.0×10\^9/L. The percentage of participants with CR, CRh or CRi will be presented.

Time frame: Up to approximately 10 weeks

Dose Escalation Phase: Rate of Minimum Residual Disease (MRD)-negative Complete Remission

MRD-negative is defined as less than 0.01% of leukemic cells were detected in bone marrow with a detection sensitivity no less than 10\^-4.

Time frame: Up to approximately 12 months

Dose Escalation Phase: Rate of Red Blood Cell and Platelet Transfusion Independence (TI)

TI is defined as no transfusion for a period of at least 1 week (7 days). The percentage of participants having TI will be presented.

Time frame: Up to approximately 24 months

Phase II: Number of Participants Who Experience at Least 1 AE

Time frame: Up to approximately 24 months

Phase II: Number of Participants who Discontinue Study Treatment Due to an AE

Time frame: Up to approximately 24 months

Phase II: Maximum Serum Drug Concentration (Cmax) of MK-1045

Blood samples will be collected to determine the maximum serum drug concentration, obtained directly from the measured value of the plasma concentration-time curve

Time frame: At designated time points up to 4 weeks

Phase II: Peripheral B Cell Depletion of MK-1045

B cell depletion will be determined at each timepoint by comparing absolute B cell numbers (as determined by flow cytometry) with those at baseline

Time frame: Baseline and at designated time points up to 4 weeks

Phase II: Peripheral Circulating T Cell Activation of of MK-1045

Peripheral circulating T cell activation will be determined at each timepoint by comparing absolute T cell numbers and T cell activation markers with those at baseline

Time frame: Baseline and at designated time points up to 4 weeks

Phase II: Concentration of Peripheral Cytokines

Blood samples will be collected to compare peripheral blood cytokine levels at various time points with those at baseline

Time frame: Baseline and at designated time points up to 4 weeks

Phase II: Percentage of participants with Antidrug Antibodies (ADA) to MK-1045

Blood samples collected at designated timepoints will be used to determine the percentage of participants who develop detectable ADAs to MK-1045

Time frame: At designated time points up to 4 weeks

Phase II: Rate of CR and CRh

Time frame: Up to approximately 10 weeks

Phase II: Rate of CR/CRh/CRi

CR is defined as follows: \< 5% blasts in the bone marrow, no circulating lymphoblasts or extramedullary disease, and full recovery of peripheral blood counts: Platelets ≥100×10\^9/L, and absolute neutrophil count (ANC) ≥1.0×10\^9/L. CRh is defined as meeting all of the following criteria: Satisfaction of all criteria for CR except partial recovery of peripheral blood counts (platelets ≥ 50 ×10\^9/L and ANC ≥ 0.5×10\^9/L). CRi is defined as follows: \<5% blasts in the bone marrow, No circulating lymphoblasts or extramedullary disease, and platelets \<100×10\^9/L and neutrophils ≥1.0×109/L or platelets ≥100 ×109/L and neutrophils \<1.0×10\^9/L. The percentage of participants with CR, CRh or CRi will be presented.

Time frame: Up to approximately 10 weeks

Phase II: Rate of Minimum Residual Disease (MRD)-negative Complete Remission

MRD-negative is defined as less than 0.01% of leukemic cells were detected in bone marrow with a detection sensitivity no less than 10\^-4.

Time frame: Up to approximately 24 months

Phase II: Rate of Red Blood Cell and Platelet TI

Red Blood Cell and Platelet TI is defined as no transfusion for a period of at least 1 week (7 days). The percentage of participants having TI will be presented.

Time frame: Up to approximately 24 months

Phase II: Proportion of Participants Undergoing Hematopoietic Stem Cell Transplantation (HSCT)

The number of participants who undergo a HSCT during study participation will be presented.

Time frame: Up to approximately 24 months

Phase II: Duration of CR

For participants who demonstrate a CR (defined as \< 5% blasts in the bone marrow, no circulating lymphoblasts or extramedullary disease, and full recovery of peripheral blood counts: Platelets ≥100×10\^9/L, and absolute neutrophil count (ANC) ≥1.0×10\^9/L) , duration of CR is defined as the time from the first documentation of a disease response of CR to the date of the first documented relapse event, or death due to any cause, whichever occurs first

Time frame: Up to approximately 24 months

Phase II: Duration of CR/CRh

Duration of CR/CRh is defined as the time from the first documentation of a disease response of CR/CRh to the date of the first documented relapse event, or death due to any cause, whichever occurs first. Only participants who demonstrate a CR (defined as \< 5% blasts in the bone marrow, no circulating lymphoblasts or extramedullary disease, and full recovery of peripheral blood counts: Platelets ≥100×10\^9/L, and absolute neutrophil count (ANC) ≥1.0×10\^9/L), or CRh \[satisfaction of all criteria for CR except partial recovery of peripheral blood counts (platelets ≥ 50 ×10\^9/L and ANC ≥ 0.5×10\^9/L)\] will be analyzed.

Time frame: Up to approximately 24 months

Phase II: Duration of CR/CRh/CRi

Duration of CR/CRh/CRi is defined as the time from the first documentation of a disease response of CR/CRh/CRi to the date of the first documented relapse event, or death due to any cause, whichever occurs first. Only participants who demonstrate a CR (defined as \< 5% blasts in the bone marrow, no circulating lymphoblasts or extramedullary disease, and full recovery of peripheral blood counts: Platelets ≥100×10\^9/L, and absolute neutrophil count (ANC) ≥1.0×10\^9/L), or CRh \[satisfaction of all criteria for CR except partial recovery of peripheral blood counts (platelets ≥ 50 ×10\^9/L and ANC ≥ 0.5×10\^9/L)\], or CRi (\<5% blasts in the bone marrow, No circulating lymphoblasts or extramedullary disease, and platelets \<100×10\^9/L and neutrophils ≥1.0×109/L or platelets ≥100 ×109/L and neutrophils \<1.0×10\^9/L) will be analyzed.

Time frame: Up to approximately 24 months

Phase II: Relapse-Free Survival (RFS)

RFS is defined as the time from the first dose of MK-1045 to the first documented relapse, or death due to any cause (whichever occurs first). In participants who achieve CR, CRh or CRi, relapse is defined as either hematological or extramedullary relapse . Hematological relapse is defined as recurrence of blasts in the blood, or \>5% blasts in bone marrow. Extramedullary relapse is defined as recurrence of extramedullary disease after a CR.

Time frame: Up to approximately 24 months

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

Overview

Conditions

Interventions

Eligibility

Locations (11)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts