Chronic Lymphocytic Leukaemia, Hematologic Malignancies, Small Lymphocytic Lymphoma
Conditions
Brief summary
Researchers are looking for new ways to treat people with B-cell cancers. In this trial, researchers will look at chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). These are blood cancers that affect B-cells in the blood, bone marrow, or lymph nodes. The goals of this trial are to learn about: * The safety of MK-1045 and if participants tolerate it. Tolerate means participants will receive trial treatment unless they need to stop treatment due to health problems. * The number of participants who respond. Respond means the number of cancer cells goes down or signs of cancer go away.
Interventions
BIOLOGICALMK-1045
Intravenous (IV) infusion
DRUGAcetaminophen (or similar antipyretic)
Oral administration as a premedication
DRUGDiphenhydramine (or similar antihistamine)
Per approved product label as a premedication
DRUGDexamethasone
IV administration as a premedication
BIOLOGICALTocilizumab
IV administration as a rescue medication
BIOLOGICALTocilizumab biosimilar
IV administration as a rescue medication
BIOLOGICALSiltuximab
IV administration as a rescue medication
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has histologically confirmed chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) active disease that is relapsed/refractory (r/r) to prior therapy. * Has confirmed CD19-positive disease. * If human immunodeficiency virus (HIV)-positive, has well-controlled HIV on antiretroviral therapy. * If hepatitis B surface antigen (HBsAg)-positive, has undetectable hepatitis B virus (HBV) viral load. * If has a history of hepatitis C virus (HCV) infection, has undetectable HCV viral load.
Exclusion criteria
* Has a history of serious cardiovascular and cerebrovascular diseases. * Has a history or presence of central nervous system disease. * Is HIV-infected with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease. * Has a diagnosis of immunodeficiency. * Has a known additional malignancy that is progressing or required active treatment within the past 2 years. * Has active autoimmune disease (not related to underlying leukemia diagnosis) that required systemic treatment in the past 2 years. * Has any active acute graft versus host disease (GvHD) or active chronic GvHD requiring systemic treatment. * Has active infection requiring systemic therapy. * Has not adequately recovered from major surgery or has ongoing surgical complications. * Has a diagnosis of Richter Transformation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohort A Part 1: Number of Participants Who Experience Dose-Limiting Toxicity (DLT) | Up to approximately 29 days | DLT will be defined as any drug-related adverse event (AE) observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next dose. |
| Cohort A Part 1: Number of Participants Who Experience an AE | Up to approximately 27 months | An AE is defined as 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. |
| Cohort A Part 1: Number of Participants Who Discontinue Study Treatment Due to an AE | Up to approximately 24 months | An AE is defined as 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. |
| Cohort A Parts 1 and 2: Objective Response Rate (ORR) | Up to approximately 66 months | ORR is defined as the percentage of participants with complete response (CR), complete response with an incomplete recovery of the participant's bone marrow (CRi), nodular partial response (nPR), or partial response (PR), per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria 2018 as assessed by blinded independent central review (BICR). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cohort A Part 2: Number of Participants Who Experience an AE | Up to approximately 27 months | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. |
| Cohort A Part 2: Number of Participants Who Discontinue Study Treatment Due to an AE | Up to approximately 24 months | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. |
| Cohort A Parts 1 and 2: Duration of Response (DOR) | Up to approximately 66 months | For participants who demonstrate a CR, CRi, nPR, or PR per iwCLL Criteria 2018 as assessed by BICR, DOR is defined as the time from the first documented evidence of CR, CRi, nPR, or PR until disease progression or death due to any cause, whichever occurs first. |
| Cohort A Parts 1 and 2: Area Under the Curve at Steady State (AUCss) of MK-1045 | Predose and at designated time points post-dose (up to approximately 24 months) | Blood samples will be collected at designated timepoints to estimate the AUCss of MK-1045. |
| Cohort A Parts 1 and 2: Maximum Concentration (Cmax) of MK-1045 | Predose and at designated time points post-dose (up to approximately 24 months) | Blood samples will be collected at designated timepoints to estimate the Cmax of MK-1045. |
| Cohort A Parts 1 and 2: Concentration Immediately Before the Next Dose Is Administered (Ctrough) of MK-1045 | Predose and at designated time points post-dose (up to approximately 24 months) | Blood samples will be collected at designated timepoints to estimate the Ctrough of MK-1045. |
| Cohort A Parts 1 and 2: Percentage of Participants Who Develop Antidrug Antibodies (ADA) to MK-1045 | Predose and at designated time points post-dose (up to approximately 24 months) | Blood samples collected at designated timepoints will be used to determine the percentage of participants who develop detectable ADAs to MK-1045. |
| Cohort A Parts 1 and 2: Percentage of Participants Who Develop MK-1045 Neutralizing Antibodies (NAb) | Predose and at designated time points post-dose (up to approximately 24 months) | Blood samples collected at designated timepoints will be used to determine the percentage of participants who develop detectable NAbs to MK-1045. |
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed