B-cell Acute Lymphoblastic Leukemia
Conditions
Brief summary
Researchers are looking for new ways to treat people with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) that is CD19 positive using a medicine called MK-1045. MK-1045 is an immunotherapy, which is a treatment that helps the immune system fight cancer. This trial will compare MK-1045 to a standard immunotherapy called blinatumomab. The goals of this trial are to learn if more people who receive MK-1045 have no cancer cells in their bone marrow compared to people who receive blinatumomab and if people who receive MK-1045 live longer compared to people who receive blinatumomab.
Detailed description
This study has 2 parts: Part 1 is a dose optimization phase of MK-1045. Part 2 is a randomized phase comparing the efficacy and safety of MK-1045 versus blinatumomab and will use the recommended dose of MK-1045 determined in Part 1
Interventions
BIOLOGICALMK-1045
Intravenous administration
BIOLOGICALBlinatumomab
Intravenous administration
DRUGAcetaminophen
Oral administration as a premedication
DRUGDiphenhydramine
Intravenous administration as a premedication
DRUGDexamethasone
Intravenous administration as a premedication
DRUGTocilizumab
Intravenous administration as a rescue medication
DRUGSiltuximab
Intravenous administration as a rescue medication
DRUGAvtozma
Intravenous administration as a rescue medication
DRUGTyenne
Intravenous administration as a rescue medication
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Review of all disease response assessments in the Phase 3 component will be performed by an independent Clinical Adjudication Committee. Reviewers will be blinded to treatment allocation and investigator assessment.
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has a confirmed diagnosis of relapsed/refractory (R/R) B-precursor acute lymphoblastic leukemia (ALL) with 5% or more lymphoblasts in the bone marrow * Has CD19+ disease, confirmed by local flow cytometry and/or immunohistochemistry testing at the time of enrollment * Has Philadelphia-negative disease, confirmed by testing, at the time of enrollment * Participants who have AEs due to previous anticancer therapies must have recovered to Grade ≤1 or baseline * Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
Exclusion criteria
* Has Burkitt's leukemia * History or presence of clinically relevant central nervous system (CNS) diseases such as epilepsy, hemorrhagic/ischemic stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, and psychosis * Has active acute graft versus host disease (GvHD) or chronic GvHD. NOTE: Participants who have received CNI for GvHD within 4 weeks before the first dose of study intervention are also excluded * History of serious cardiovascular and cerebrovascular diseases. * HIV-infection with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease * Received prior treatment with blinatumomab within 12 weeks for Part 1 and 24 weeks for Part 2 before the first dose of study intervention (individuals known to be refractory or intolerant to blinatumomab are to be excluded). Refractory to blinatumomab is defined as failure to achieve a response after at least 2 cycles of previous blinatumomab treatment * Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention * Known additional malignancy that is progressing or has required active treatment within the past 2 years * Isolated extramedullary disease (EMD) * Active autoimmune disease unrelated to ALL that has required systemic treatment in the past 2 years or history of autoimmune disease with potential CNS involvement * Active infection requiring systemic therapy * Has not adequately recovered from major surgery or have ongoing surgical complications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants with Complete Remission (CR) in Study Part 1 and Part 2 | 3 treatment cycles (up to approximately 126 days; each cycle is up to 42 days; cycle lengths vary between cycle and arm) | CR is defined as: * No circulating lymphoblasts * Extramedullary disease negative * Trilineage hematopoiesis (TLH) and \<5% leukemic blasts * Absolute neutrophil count (ANC) ≥1000/μL * Platelets ≥100,000/μL * No platelet transfusions in the last 7 days * No administration of short-acting granulocyte colony-stimulating factor (G-CSF) and long-acting G-CSF in the last 3 and 14 days, respectively |
| Percentage of Participants Who Experience an Adverse Event (AE) in Study Part 1 | 3 treatment cycles (up to approximately 126 days; each cycle is up to 42 days; cycle lengths vary between cycle and arm) | 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. The percentage of participants with at least 1 AE will be presented. |
| Percentage of Participants Who Discontinue Study Intervention Due to an AE in Study Part 1 | 3 treatment cycles (up to approximately 126 days; each cycle is up to 42 days; cycle lengths vary between cycle and arm) | 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. The percentage of participants who discontinue study intervention due to an AE will be presented. |
| Overall Survival (OS) in Study Part 2 | Up to approximately 7 years | OS is the time from randomization to death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) in Study Part 1 | Up to approximately 7 years | OS is the time from randomization to death due to any cause. |
| Percentage of Participants that achieve Minimal Residual Disease (MRD) in Study Part 1 and Part 2 | 3 treatment cycles (up to approximately 126 days; each cycle is up to 42 days; cycle lengths vary between cycle and arm) | MRD is defined as no detectable leukemia cells below a threshold of at least 10\^-4. |
| Percentage of Participants that achieve CR/CR with partial hematologic recovery (CRh)/CR with incomplete count recovery (CRi) in Study Part 1 and Part 2 | 3 treatment cycles (up to approximately 126 days; each cycle is up to 42 days; cycle lengths vary between cycle and arm) | For participants who demonstrate CR or CRh or CRi, duration of remission is defined as the time from the first documented evidence of CR or CRh or CRi (whichever is earlier) until disease progression, relapse, or death due to any cause, whichever occurs first. CR is defined as: * No circulating lymphoblasts * Extramedullary disease negative * Trilineage hematopoiesis (TLH) and \<5% leukemic blasts * Absolute neutrophil count (ANC) ≥1000/μL * Platelets ≥100,000/μL * No platelet transfusions in the last 7 days * No administration of short-acting granulocyte colony-stimulating factor (G-CSF) and long-acting G-CSF in the last 3 and 14 days, respectively CRh is the same as CR but with less stringent requirements for platelet count (≥50,000/μL) and ANC (≥500/μL). CRi is the same as CR but without recovery of platelet count or without recovery of ANC (platelets \<100,000/μL and ANC ≥1000/μL or platelets ≥100,000/μL and ANC \<1000/μL. |
| Percentage of Participants with CR or CRh in Study Part 2 | 3 treatment cycles (up to approximately 126 days; each cycle is up to 42 days; cycle lengths vary between cycle and arm) | The percentage of participants who meet either CR or CRh requirements will be presented. CR is defined as: * No circulating lymphoblasts * Extramedullary disease negative * Trilineage hematopoiesis (TLH) and \<5% leukemic blasts * Absolute neutrophil count (ANC) ≥1000/μL * Platelets ≥100,000/μL * No platelet transfusions in the last 7 days * No administration of short-acting granulocyte colony-stimulating factor (G-CSF) and long-acting G-CSF in the last 3 and 14 days, respectively CRh is the same as CR but with less stringent requirements for platelet count (≥50,000/μL) and ANC (≥500/μL). |
| Duration of CR (DOR-CR) in Study Part 2 | Up to approximately 7 years | For participants who demonstrate CR, duration of remission is defined as the time from the first documented evidence of CR until disease progression, relapse, or death due to any cause, whichever occurs first. CR is defined as: * No circulating lymphoblasts * Extramedullary disease negative * Trilineage hematopoiesis (TLH) and \<5% leukemic blasts * Absolute neutrophil count (ANC) ≥1000/μL * Platelets ≥100,000/μL * No platelet transfusions in the last 7 days * No administration of short-acting granulocyte colony-stimulating factor (G-CSF) and long-acting G-CSF in the last 3 and 14 days, respectively |
| Duration of CR/CRh (DOR-CR/CRh) in Study Part 2 | Up to approximately 7 years | For participants who demonstrate CR or CRh, duration of remission is defined as the time from the first documented evidence of CR or CRh (whichever is earlier) until disease progression, relapse, or death due to any cause, whichever occurs first. CR is defined as: * No circulating lymphoblasts * Extramedullary disease negative * Trilineage hematopoiesis (TLH) and \<5% leukemic blasts * Absolute neutrophil count (ANC) ≥1000/μL * Platelets ≥100,000/μL * No platelet transfusions in the last 7 days * No administration of short-acting granulocyte colony-stimulating factor (G-CSF) and long-acting G-CSF in the last 3 and 14 days, respectively CRh is the same as CR but with less stringent requirements for platelet count (≥50,000/μL) and ANC (≥500/μL). |
| Duration of CR/CRh/CRi (DOR-CR/CRh/CRi) in Study Part 2 | Up to approximately 7 years | For participants who demonstrate CR or CRh or CRi, duration of remission is defined as the time from the first documented evidence of CR or CRh or CRi (whichever is earlier) until disease progression, relapse, or death due to any cause, whichever occurs first. CR is defined as: * No circulating lymphoblasts * Extramedullary disease negative * Trilineage hematopoiesis (TLH) and \<5% leukemic blasts * Absolute neutrophil count (ANC) ≥1000/μL * Platelets ≥100,000/μL * No platelet transfusions in the last 7 days * No administration of short-acting granulocyte colony-stimulating factor (G-CSF) and long-acting G-CSF in the last 3 and 14 days, respectively CRh is the same as CR but with less stringent requirements for platelet count (≥50,000/μL) and ANC (≥500/μL). CRi is the same as CR but without recovery of platelet count or without recovery of ANC (platelets \<100,000/μL and ANC ≥1000/μL or platelets ≥100,000/μL and ANC \<1000/μL. |
| Event Free Survival (EFS) in Study Part 2 | Up to approximately 7 years | The time from randomization to the first documented disease progression, relapse, or death due to any cause, whichever occurs first. |
| Percentage of participants that proceed to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Study Part 2 | Up to approximately 7 years | The use of allo-HSCT treatment after randomization. |
| Percentage of Participants Who Experience an AE in Study Part 2 | Up to approximately 7 years | 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. The percentage of participants with at least 1 AE will be presented. |
| Percentage of Participants Who Discontinue Study Intervention Due to an AE in Study Part 2 | Up to approximately 7 years | 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. The percentage of participants who discontinue study intervention due to an AE will be presented. |
Countries
Denmark, Israel, Japan, Netherlands, Spain
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed