Follicular Lymphoma
Conditions
Brief summary
Researchers are looking for new ways to treat follicular lymphoma (FL). A standard (usual) treatment for FL includes a targeted therapy called rituximab and chemotherapy. In this study, researchers want to learn if giving a study medicine called MK-1045 and rituximab can treat FL. MK-1045 is a type of treatment called immunotherapy. The goals of this study are to learn: * About the safety of MK-1045 and rituximab, and if people tolerate them when given together * If people who receive MK-1045 and rituximab have the cancer go away * If people who receive MK-1045 and rituximab live longer without their cancer getting worse compared to those who receive standard treatment (rituximab and chemotherapy)
Interventions
BIOLOGICALMK-1045
Intravenous (IV) infusion
BIOLOGICALRituximab
IV infusion
BIOLOGICALRituximab biosimilar
IV infusion
DRUGBendamustine
IV infusion
DRUGCyclophosphamide
IV infusion
DRUGVincristine
IV infusion
DRUGPrednisone
Per approved product label
DRUGPrednisolone
Per approved product label
DRUGDoxorubicin Hydrochloride
IV infusion
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has biopsy-proven, previously untreated, histologically confirmed cluster of differentiation (CD)19-positive and CD20-positive classical follicular lymphoma (FL), with Ann Arbor Stage II-IV disease and a Follicular Lymphoma International Prognostic Index (FLIPI) score of 2-5. * Has radiographically measurable disease per the Lugano Response Criteria. * Has provided a newly obtained core or excisional biopsy or archival tissue of a tumor lesion not previously irradiated. * If human immunodeficiency virus (HIV)-positive, has well-controlled HIV on antiretroviral therapy (ART). * If hepatitis B surface antigen (HBsAg)-positive, has undetectable hepatitis B virus (HBV) viral load and has received HBV antiviral therapy for at least 4 weeks and will continue it. * If history of hepatitis C virus (HCV) infection, has undetectable HCV viral load.
Exclusion criteria
* Has received prior systemic anticancer therapy or radiotherapy for FL. * Has follicular large B-cell lymphoma or any other subtype of FL other than classical FL. * Has FL that has transformed into a more aggressive type of lymphoma. * History or presence of clinically relevant central nervous system (CNS) diseases. * Has history of serious cardiovascular and cerebrovascular diseases. * Is HIV-infected with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease. * Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy. * Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. * Has known active CNS lymphoma or involvement. * Has an active autoimmune disease that has required systemic treatment in the past 2 years. * Has active infection requiring systemic therapy. * Has chronic liver disease, including liver cirrhosis of Child-Pugh class B or C. * Has not adequately recovered from major surgery or has ongoing surgical complications.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants Who Experience an Adverse Event (AE) | Up to approximately 15 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. |
| Part 1: Number of Participants Who Discontinue Study Treatment Due to an AE | Up to approximately 12 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. |
| Part 1: Number of Participants Who Experience Dose Limiting Toxicity (DLT) | Up to approximately 36 days | DLT will be defined as any drug-related AE observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next cycle. |
| Part 1: Complete Response (CR) Rate | Up to approximately 60 months | For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) per Lugano response criteria. CR rate is defined as the percentage of participants who experience a CR. The CR rate as assessed by physician investigator will be presented. |
| Part 2: Progression-Free Survival (PFS) | Up to approximately 63 months | PFS is defined as the time from randomization to the first documented disease progression per Lugano response criteria by Blinded Independent Central Review (BICR) or death due to any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Objective Response Rate (ORR) | Up to approximately 60 months | ORR is defined as the percentage of participants with CR (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Lugano response criteria. The percentage of participants who experience CR or PR as assessed by physician investigator will be presented. |
| Part 1: Duration of CR | Up to approximately 60 months | For participants who demonstrate CR (CR: disappearance of all target lesions) at end of treatment per Lugano response criteria, defined as the time from the first documented evidence of CR until disease progression or death due to any cause, whichever occurs first. |
| Part 1: Area Under the Concentration-Time Curve at Steady State (AUCss) of MK-1045 | Predose and at designated time points post-dose (up to approximately 12 months) | Blood samples will be collected at multiple time points to estimate the AUCss of MK-1045. |
| Part 1: Maximum Concentration (Cmax) of MK-1045 | Predose and at designated time points post-dose (up to approximately 12 months) | Blood samples will be collected at multiple time points to estimate the Cmax of MK-1045. |
| Part 1: Trough Concentration (Ctrough) of MK-1045 | Predose and at designated time points post-dose (up to approximately 12 months) | Blood samples will be collected at multiple time points to estimate the Ctrough of MK-1045. |
| Part 2: CR Rate at 30 Months | 30 months | For participants who demonstrate a confirmed CR (CR: disappearance of all target lesions) per Lugano response criteria. CR rate is defined as the percentage of participants who experience a CR by month 30. The CR rate as assessed by BICR at month 30 will be presented. |
| Part 2: ORR | Up to approximately 63 months | ORR is defined as the percentage of participants with CR (CR: disappearance of all target lesions) or PR (PR: at least a 30% decrease in the sum of diameters of target lesions) per Lugano response criteria. The percentage of participants who experience CR or PR as assessed by BICR will be presented. |
| Part 2: Overall Survival (OS) | Up to approximately 63 months | OS is defined as the time from randomization to death due to any cause. |
| Part 2: Event-Free Survival (EFS) | Up to approximately 63 months | EFS is defined as the time randomization to the first documented disease progression per Lugano response criteria by BICR, death due to any cause, initiation of a new anticancer therapy or a positive biopsy for residual disease, whichever occurs first. |
| Part 2: Duration of CR | Up to approximately 63 months | For participants who demonstrate CR (CR: disappearance of all target lesions) per Lugano response criteria by BICR, defined as the time from the first documented evidence of CR until disease progression or death due to any cause, whichever occurs first. |
| Part 2: Number of Participants Who Experience an AE | Up to approximately 15 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. |
| Part 2: Number of Participants Who Discontinue Study Treatment Due to an AE | Up to approximately 12 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. |
| Part 2: Change From Baseline in Health-Related Quality Of Life (HRQoL) on Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Trial Outcome Index (TOI) | Baseline and up to approximately month 13 | The FACT-Lym is a 42-item questionnaire designed to measure HRQoL and cancer-specific symptoms in non-Hodgkin lymphoma patients. Subscales include FACT-General (FACT-G), FACT-Trial Outcome Index (FACT-TOI), FACT-Lym total score (FACT-Lym TS), and the Lymphoma subscale (Lym S). The Lym S has a single domain consisting of 15 items specific to lymphoma burden with a score ranging from 0 to 60. FACT-G has 4 well-being domains, physical (7 items), social/family (7), emotional (6), and functional (7), with scores ranging from 0 to 108. FACT-TOI combines FACT-G's physical and functional domains with Lym S, with scores ranging from 0 to 116. FACT-Lym TS combines FACT-G with Lym S, with scores ranging from 0 to 168. The scoring of FACT-Lym is on a 5-point Likert scale from 0 to 4, with 0= not at all, 1= a little bit, 2= somewhat, 3=quite a bit, 4=very much. The higher the score the better the quality of life. |
| Part 2: Change From Baseline in HRQoL on FACT-Lym Total Score | Baseline and up to approximately month 13 | The FACT-Lym is a 42-item questionnaire designed to measure HRQoL and cancer-specific symptoms in non-Hodgkin lymphoma patients. Subscales include FACT-General (FACT-G), FACT-Trial Outcome Index (FACT-TOI), FACT-Lym total score (FACT-Lym TS), and the Lymphoma subscale (Lym S). The Lym S has a single domain consisting of 15 items specific to lymphoma burden with a score ranging from 0 to 60. FACT-G has 4 well-being domains, physical (7 items), social/family (7), emotional (6), and functional (7), with scores ranging from 0 to 108. FACT-TOI combines FACT-G's physical and functional domains with Lym S, with scores ranging from 0 to 116. FACT-Lym TS combines FACT-G with Lym S, with scores ranging from 0 to 168. The scoring of FACT-Lym is on a 5-point Likert scale from 0 to 4, with 0= not at all, 1= a little bit, 2= somewhat, 3=quite a bit, 4=very much. The higher the score the better the quality of life. |
| Part 2: Change From Baseline in HRQoL on FACT-Lym Physical Well-being (PWB) (Items General Physical [GP]1 Through GP7) | Baseline and up to approximately month 13 | The FACT-Lym is a 42-item questionnaire designed to measure HRQoL and cancer-specific symptoms in non-Hodgkin lymphoma patients. Subscales include FACT-General (FACT-G), FACT-Trial Outcome Index (FACT-TOI), FACT-Lym total score (FACT-Lym TS), and the Lymphoma subscale (Lym S). The Lym S has a single domain consisting of 15 items specific to lymphoma burden with a score ranging from 0 to 60. FACT-G has 4 well-being domains, physical (7 items), social/family (7), emotional (6), and functional (7), with scores ranging from 0 to 108. FACT-TOI combines FACT-G's physical and functional domains with Lym S, with scores ranging from 0 to 116. FACT-Lym TS combines FACT-G with Lym S, with scores ranging from 0 to 168. The scoring of FACT-Lym is on a 5-point Likert scale from 0 to 4, with 0= not at all, 1= a little bit, 2= somewhat, 3=quite a bit, 4=very much. The higher the score the better the quality of life. |
Countries
Israel, Spain, Taiwan, Turkey (Türkiye), United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed