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| ID | Type | Description | Link |
|---|---|---|---|
| MK-1045-002 | Other Identifier | MSD | |
| CN201-103 | Other Identifier | Curon Biopharmaceutical Co., LTD |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MK-1045: Dose Escalation Phase- Adult Cohort | Experimental | Adults in the dose escalation phase will receive a target dose level of MK-1045 from 600 μg to 120,000 μg, administered by intravenous (IV) infusion. MK-1045 will be administered once per week, in treatment cycles defined as 4 weeks of MK-1045 treatment. |
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| MK-1045 : Dose Escalation Phase- Pediatric Cohort | Experimental | Pediatric participants will receive a target dose level of MK-1045 from 320 μg to 60000 μg, with dosing further based upon weight. MK-1045 will be administered by IV infusion once per week, in treatment cycles defined as 4 weeks of MK-1045 treatment. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK-1045 | Drug | 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. Each 4 week treatment cycle is followed by a 2-week treatment-free interval. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to approximately 24 months |
| Dose Escalation Phase: Number of Participants who Discontinue Study Treatment Due to an 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. | 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. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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 |
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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:
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:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Toll Free Number | Contact | 1-888-577-8839 | Trialsites@msd.com |
| Name | Affiliation | Role |
|---|---|---|
| Jianxiang Wang, Dr. | Institute of Hematology & Blood Diseases Hospital, China | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Second Affiliated Hospital of Third Military Medical University ( Site 0008) | Recruiting | Chongqing | Chongqing Municipality | 400037 | China |
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| Label | URL |
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| Merck Clinical Trials Information | View source |
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| Up to approximately 21 months |
| Phase II: Complete Remission (CR) Rate | 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. The number of participants with CR will be presented. | Up to approximately 10 weeks |
Blood samples will be collected to determine the AUC0-inf of MK-1045. |
| 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 | 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 | 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 | 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 | 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 | At designated time points up to approximately 12 months |
| Dose Escalation Phase: Apparent Terminal Half Life (t1/2) | Blood samples will be collected to determine the t1/2 of MK-1045 | At designated time points up to approximately 24 weeks |
| Dose Escalation Phase: Apparent Clearance (CL) of MK-1045 | Blood samples will be collected to determine the CL of MK-1045 | At designated time points up to approximately 24 weeks |
| Dose Escalation Phase: Apparent Volume of Distribution (Vz) of MK-1045 | Blood samples will be collected to determine the Vz of MK-1045 | At designated time points up to approximately 24 weeks |
| 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 | At designated time points up to approximately 24 weeks |
| Dose Escalation Phase: Mean Residence Time (MRT) of MK-1045 | Blood samples will be collected to determine the MRT of MK-1045 | 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 | 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 | 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 | 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) | 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). The percentage of participants with CR or CRh will be presented. | 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. | 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. | 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. | Up to approximately 24 months |
| Phase II: Number of Participants Who Experience at Least 1 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. | Up to approximately 24 months |
| Phase II: Number of Participants who Discontinue Study Treatment Due to an 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. | 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 | At designated time points up to 4 weeks |
| Phase II: Concentration at End of Dosing Interval (Ctrough) of MK-1045 | Blood samples will be collected to determine the Ctrough of MK-1045 | 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 | 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 | 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 | 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 | At designated time points up to 4 weeks |
| Phase II: Rate of CR and CRh | 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). The percentage of participants with CR or CRh will be presented. | 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. | 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. | 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. | 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. | 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 | 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. | 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. | 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. | Up to approximately 24 months |
| Phase II: Overall Survival (OS) | OS is the time from date of first study treatment to the date of death due to any reason. | Up to approximately 24 months |
| Southern Medical University Nanfang Hospital ( Site 0004) | Recruiting | Guangzhou | Guangdong | 510515 | China |
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| The Second Hospital of Hebei Medical University ( Site 0003) | Recruiting | Shijiazhuang | Hebei | 050000 | China |
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| The First Hospital of Harbin ( Site 0005) | Recruiting | Harbin | Heilongjiang | 150010 | China |
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| Henan Cancer Hospital-hematology department ( Site 0002) | Recruiting | Zhengzhou | Henan | 450008 | China |
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| Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology ( Site 0010) | Recruiting | Wuhan | Hubei | 430022 | China |
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| Tongji Hospital affiliated to Tongji Medical College of HUST ( Site 0006) | Recruiting | Wuhan | Hubei | 430030 | China |
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| The Affiliated Hospital of Xuzhou Medical University ( Site 0007) | Active, not recruiting | Xuzhou | Jiangsu | 221002 | China |
| West China Second University Hospital, Sichuan University ( Site 0011) | Completed | Chengdu | Sichuan | 610000 | China |
| Hematology Hospital of Chinese Academy of Medical Sciences ( Site 0001) | Recruiting | Tianjin | Tianjin Municipality | 301617 | China |
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| The Children's Hospital of Zhejiang University School of Medicine ( Site 0009) | Completed | Hangzhou | Zhejiang | 310003 | China |
| ID | Term |
|---|---|
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| ID | Term |
|---|---|
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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