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.
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
Failure to achieve complete remission after initial induction therapy;
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
Single group
MK-1045
DrugMK-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.
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.
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.
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.
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.
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
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.
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
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
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