B-cell Acute Lymphoblastic Leukemia, Diffuse Large B-cell Lymphoma, Burkitt Lymphoma, Neuroblastoma, Ewing Sarcoma
Conditions
Brief summary
Substudy 01A is part of a platform study. The purpose of this study is to assess the efficacy and safety of zilovertamab vedotin in pediatric participants with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), diffuse large B-cell lymphoma (DLBCL)/Burkitt lymphoma, or neuroblastoma and in pediatric and young adult participants with Ewing sarcoma.
Interventions
BIOLOGICALZilovertamab vedotin
Administered via IV infusion
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 25 Years
Healthy volunteers
No
Inclusion criteria
The main inclusion and
Exclusion criteria
include but are not limited to the following: Inclusion Criteria: * For hematological malignancies: Confirmed diagnosis of B-precursor B-ALL or DLBCL/Burkitt lymphoma according to World Health Organization (WHO) classification of neoplasms of the lymphoid tissues. * For solid tumor malignancies: Histologically confirmed diagnosis of neuroblastoma or Ewing sarcoma.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants from 1 to <18 years of Age Who Experience a Dose-Limiting Toxicity (DLT) | Up to 42 days | Number of participants experiencing toxicities that are possibly, probably, or definitely related to study therapy; that meet pre-defined severity criteria; and result in a change in the given dose. |
| Part 1: Number of Participants from 1 to <18 years of Age Who Experience One or More Adverse Events (AEs) | Up to approximately 54 months | An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. 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 medicinal product and does not imply any judgment about causality. The number of participants in Part 1 who experience at least 1 AE will be presented. |
| Part 1: Number of Participants from 1 to <18 years of Age Who Discontinue Study Treatment Due to AEs | Up to approximately 54 months | An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. 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 medicinal product and does not imply any judgment about causality. The number of participants in Part 1 who discontinue study treatment due to an AE will be presented. |
| Part 1: Number of Participants from 1 to <18 years of Age Who Receive Dose Modification Due to AEs | Up to approximately 54 months | An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. 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 medicinal product and does not imply any judgment about causality. The number of participants in Part 1 who receive a dose modification due to an AE will be presented. |
| Part 1 and Part 2: Objective Response (OR) for Participants with B-Cell Acute Lymphoblastic Leukemia (B-ALL) | Up to approximately 54 months | OR for participants with B-ALL is defined as complete response (CR) or complete response with incomplete hematologic recovery (CRi) based on investigator's assessment per Ponte-di-Legno Consortium criteria. For Part 1 and Part 2, the OR for participants with B-ALL as assessed by investigator will be presented. |
| Part 1 and Part 2: OR for Participants with Diffuse Large B-Cell Lymphoma (DLBCL)/Burkitt Lymphoma, Neuroblastoma, and Ewing Sarcoma | Up to approximately 54 months | OR for participants with DLBCL/Burkitt lymphoma, neuroblastoma, and Ewing sarcoma is defined as complete response (CR) or partial response (PR) based on investigator's assessment per International Pediatric Non-Hodgkin Lymphoma (IPNHL) Response Criteria for participants with DLBCL/Burkitt lymphoma, per International Neuroblastoma Response Criteria (INRC) for neuroblastoma, and per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for Ewing sarcoma. For Part 1 and Part 2, the OR for participants with DLBCL/Burkitt lymphoma, neuroblastoma, and Ewing sarcoma as assessed by investigator will be presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 and Part 2: Area Under the Curve (AUC) of Total Antibody | Predose on Day 1 of Cycles 1 through 6 and every 4 cycles thereafter, at end of infusion on Day 1 of Cycles 1 and 3, and on Days 3, 8, and 15 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 54 months) | Blood samples collected at designated time points will be used to determine the AUC of total antibody. |
| Part 1 and Part 2: Maximum Plasma Concentration (Cmax) of Total Antibody | Predose on Day 1 of Cycles 1 through 6 and every 4 cycles thereafter, at end of infusion on Day 1 of Cycles 1 and 3, and on Days 3, 8, and 15 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 54 months) | Blood samples collected at designated time points will be used to determine the Cmax of total antibody. |
| Part 1 and Part 2: Plasma Trough Concentration (Ctrough) of Total Antibody | Predose on Day 1 of Cycles 1 through 6 and every 4 cycles thereafter, at end of infusion on Day 1 of Cycles 1 and 3, and on Days 3, 8, and 15 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 54 months) | Blood samples collected at designated time points will be used to determine the Ctrough of total antibody. |
| Part 1 and Part 2: Apparent Terminal Half-life (t1/2) of Total Antibody | Predose on Day 1 of Cycles 1 through 6 and every 4 cycles thereafter, at end of infusion on Day 1 of Cycles 1 and 3, and on Days 3, 8, and 15 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 54 months) | Blood samples collected at designated time points will be used to determine the t1/2 of total antibody. |
| Part 1 and Part 2: AUC of Antibody-Drug Conjugate (ADC) | Predose on Day 1 of Cycles 1 through 6 and every 4 cycles thereafter, at end of infusion on Day 1 of Cycles 1 and 3, and on Days 3, 8, and 15 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 54 months) | Blood samples collected at designated time points will be used to determine the AUC of ADC. |
| Part 1 and Part 2: Cmax of ADC | Predose on Day 1 of Cycles 1 through 6 and every 4 cycles thereafter, at end of infusion on Day 1 of Cycles 1 and 3, and on Days 3, 8, and 15 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 54 months) | Blood samples collected at designated time points will be used to determine the Cmax of ADC. |
| Part 1 and Part 2: Ctrough of ADC | Predose on Day 1 of Cycles 1 through 6 and every 4 cycles thereafter, at end of infusion on Day 1 of Cycles 1 and 3, and on Days 3, 8, and 15 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 54 months) | Blood samples collected at designated time points will be used to determine the Ctrough of ADC. |
| Part 1 and Part 2: t1/2 of ADC | Predose on Day 1 of Cycles 1 through 6 and every 4 cycles thereafter, at end of infusion on Day 1 of Cycles 1 and 3, and on Days 3, 8, and 15 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 54 months) | Blood samples collected at designated time points will be used to determine the t1/2 of ADC. |
| Part 1 and Part 2: AUC of Monomethyl Auristatin E (MMAE) | Predose on Day 1 of Cycles 1 through 6 and every 4 cycles thereafter, at end of infusion on Day 1 of Cycles 1 and 3, and on Days 3, 8, and 15 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 54 months) | Blood samples collected at designated time points will be used to determine the AUC of MMAE. |
| Part 1 and Part 2: Cmax of MMAE | Predose on Day 1 of Cycles 1 through 6 and every 4 cycles thereafter, at end of infusion on Day 1 of Cycles 1 and 3, and on Days 3, 8, and 15 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 54 months) | Blood samples collected at designated time points will be used to determine the Cmax of MMAE. |
| Part 1 and Part 2: Ctrough of MMAE | Predose on Day 1 of Cycles 1 through 6 and every 4 cycles thereafter, at end of infusion on Day 1 of Cycles 1 and 3, and on Days 3, 8, and 15 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 54 months) | Blood samples collected at designated time points will be used to determine the Ctrough of MMAE. |
| Part 1 and Part 2: t1/2 of MMAE | Predose on Day 1 of Cycles 1 through 6 and every 4 cycles thereafter, at end of infusion on Day 1 of Cycles 1 and 3, and on Days 3, 8, and 15 of Cycles 1 and 3. Each cycle is 21 days. (Up to approximately 54 months) | Blood samples collected at designated time points will be used to determine the t1/2 of MMAE. |
| Part 2: Number of Participants Who Experience One or More AEs | Up to approximately 54 months | An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. 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 medicinal product and does not imply any judgment about causality. The number of participants in Part 2 who experience at least 1 AE will be presented. |
| Part 2: Number of Participants Who Discontinue Study Treatment Due to AEs | Up to approximately 54 months | An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. 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 medicinal product and does not imply any judgment about causality. The number of participants in Part 2 who discontinue study treatment due to an AE will be presented. |
| Part 2: Number of Participants Who Receive Dose Modification Due to AEs | Up to approximately 54 months | An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. 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 medicinal product and does not imply any judgment about causality. The number of participants in Part 2 who receive a dose modification due to an AE will be presented. |
| Part 1 and Part 2: Incidence of Antidrug Antibodies (ADAs) to Zilovertamab Vedotin | Predose on Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 4 cycles thereafter. Each cycle is 21 days. (Up to approximately 54 months) | Blood samples collected at designated timepoints will be used to determine the ADA response to zilovertamab vedotin. The incidence of ADAs over time will be presented. |
| Part 1 and Part 2: Duration of Response (DOR) | Up to approximately 54 months | DOR is defined as the time from the first documented evidence of CR/CRi for B-ALL or CR/PR for DLBCL/Burkitt lymphoma, Ewing sarcoma, and neuroblastoma until disease progression or death due to any cause, whichever occurs first. For participants under 1-year of age, the time from the first dose will start from the first dose a participant receives during Part 2. |
| Part 1 and Part 2: Percentage of Participants with DLBCL/Burkitt Lymphoma Who Receive Stem Cell Transplant (SCT) | Up to approximately 54 months | The percentage of participants with DLBCL/Burkitt Lymphoma who go on to receive SCT will be presented. |
| Part 1 and Part 2: Percentage of Participants with B-ALL Who Receive SCT | Up to approximately 54 months | The percentage of participants with B-ALL who go on to receive SCT will be presented. |
| Part 1 and Part 2: Percentage of Participants with B-ALL Who Receive Chimeric Antigen Receptor T (CAR-T) | Up to approximately 54 months | The percentage of participants with B-ALL who go on to receive CAR-T will be presented. |
Countries
Australia, Belgium, Brazil, Canada, Chile, Colombia, Czechia, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Netherlands, Slovakia, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed