Follicular Lymphoma
Conditions
Brief summary
This study will evaluate the safety, pharmacokinetics, and anti-tumor activity of MK-8808 in combination with cyclophosphamide, vincristine, and prednisolone (CVP), and as a single agent, for participants with B-lymphocyte antigen cluster of differentiation 20 (CD20)-positive follicular lymphoma who have had no prior chemotherapy. The primary study hypothesis is that MK-8808 will be safe and well tolerated in combination with CVP and as a single agent.
Detailed description
The study was terminated early by the Sponsor due to business reasons. All participants were discontinued from MK-8808 + CVP, but could continue to receive maintenance therapy with MabThera™ (rituximab) per standard of care.
Interventions
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histological diagnosis of CD20-positive follicular lymphoma, Grade 1, 2, or 3a (World Health Organization \[WHO\] 2008 classification) based on an excisional or incisional lymph node biopsy or a bone marrow biopsy. * Ann Arbor Stage III or IV disease. * Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. * Life expectancy \>3 months with no expected need of immediate intervention to treat life-threatening complications. * Adequate organ function. * Participants must agree to use an adequate method of contraception starting with the first dose of study drug through 12 months (for females) or 90 days (for males) after the last dose of study drug.
Exclusion criteria
* Histological Grade 3b or with \>50% diffuse architectural pattern. * Circulating malignant cells \>25,000/mm\^3 * Presence or history of central nervous system (CNS) disease (either CNS lymphoma or lymphomatous meningitis). * Prior treatment with chemotherapy, rituximab, any other anti-CD20 compound, or any other type of anti-cancer compounds. * Radiotherapy within 2 months prior to Cycle 1 Day 1. * Current participation or has participated in a study with an investigational compound within 30 days prior to Cycle 1 Day 1. * Concomitant disease that requires continuous therapy with prednisone at doses \>20 mg per day. * Any medical contraindication for prednisolone as being dosed in the CVP regimen. * Poorly controlled diabetes mellitus, as defined by institutional or local standards. * Grade \>2 peripheral neuropathy. * Has one of the following: 1. is human immunodeficiency virus (HIV)-positive 2. is Hepatitis B surface antigen positive (HBsAg+) or is positive for antibodies to Hepatitis B core antigen (anti-HBcAg+) 3. has antibodies to Hepatitis C virus * Has one or more of the following: 1. Active tuberculosis based on institutional diagnostic criteria and local practice guidelines. 2. Evidence of a tuberculosis infection based on a chest X-ray (CXR) or computed tomography (CT) scan performed within 3 months of dosing. 3. History of a tuberculosis infection. * Major surgical procedure within 4 weeks prior to Cycle 1 Day 1. * Regular use (including recreational use) of any illicit drugs or recent history (within the last year) of drug or alcohol abuse or dependence. * Pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Clinical and Laboratory Adverse Events (AEs) During MK-8808/CVP Combination Therapy | From first dose of combination therapy up to 24 weeks | An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment. |
| Number of Participants Experiencing Clinical and Laboratory AEs During MK-8808 Maintenance Therapy | From first dose of single agent MK-8808 up to 2 years | An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lowest Concentration (Ctrough) of Plasma Levels of MK-8808 When Used in Combination With CVP | Pre-dose and end of infusion in each 21-day cycle and at end of therapy visit (up to 24 weeks) | Ctrough is a measure of the lowest level of drug in the plasma over time, using plasma samples collected at specified time points. |
| Maximum Concentration (Cmax) of Plasma Levels of MK-8808 When Used in Combination With CVP | Pre-dose and end of infusion in each 21-day cycle and at end of therapy visit (up to 24 weeks) | Cmax is a measure of the maximum concentration of the drug in the plasma as measured using plasma samples taken over specified time points. |
| Clinical Response of Tumor to MK-8808/CVP Combination Therapy | Up to 2 years | The response of the tumor to MK-8808/CVP combination therapy was radiographically assessed using Response Criteria Evaluation in Solid Tumors (RECIST). Response categories of partial response (PR), complete resonse (CR), and uncomfirmed (CRu) central review. |
| Ctrough of Plasma Levels of MK-8808 When Used as Single Agent Maintenance | Predose and end of infusion in every other cycle and at end of therapy visit (up to 2 years) | Ctrough is a measure of the lowest level of drug in the plasma over time, using plasma samples collected at specified time points. |
| Cmax of Plasma Levels of MK-8808 During Single Agent Maintenance Therapy | Predose and end of infusion in every other cycle and at end of therapy visit (up to 2 years) | Cmax is a measure of the maximum amount of drug in the plasma over time using samples taken at specified time points. |
Participant flow
Recruitment details
The study was terminated early by the Sponsor due to business reasons. All participants were discontinued from MK-8808 on 18 March 2014, but could continue to receive maintenance therapy with rituximab per standard of care.
Participants by arm
| Arm | Count |
|---|---|
| MK-8808 Combination Therapy Participants received MK-8808 375 mg/m\^2 intravenously (IV) + cyclophosphamide 750 mg/m\^2 IV + vincristine 1.4 mg/m\^2 IV (maximum dose of 2 mg IV) on Day 1 each cycle, plus prednisolone 40 mg/m\^2, orally on Days 1 to 5 of each cycle for a maximum of 8 cycles. Participants receiving clinical benefit could remain on MK-8808 375 mg/m\^2 IV starting 8 weeks after last dose of combination therapy, every 2 months for up to 2 years. | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Progressive disease | 2 |
| Overall Study | Switched to rituximab | 4 |
Baseline characteristics
| Characteristic | MK-8808 Combination Therapy |
|---|---|
| Age, Continuous | 56.1 Years STANDARD_DEVIATION 16.4 |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 7 |
| serious Total, serious adverse events | 1 / 7 |
Outcome results
Primary
Number of Participants Experiencing Clinical and Laboratory Adverse Events (AEs) During MK-8808/CVP Combination Therapy
An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment.
Time frame: From first dose of combination therapy up to 24 weeks
Population: All participants receiving at least one dose of any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-8808 Combination Therapy | Number of Participants Experiencing Clinical and Laboratory Adverse Events (AEs) During MK-8808/CVP Combination Therapy | 6 Participants |
Primary
Number of Participants Experiencing Clinical and Laboratory AEs During MK-8808 Maintenance Therapy
An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment.
Time frame: From first dose of single agent MK-8808 up to 2 years
Population: No participants progressed to MK-8808 single agent maintenance therapy; this outcome measure was not assessed.
Secondary
Clinical Response of Tumor to MK-8808/CVP Combination Therapy
The response of the tumor to MK-8808/CVP combination therapy was radiographically assessed using Response Criteria Evaluation in Solid Tumors (RECIST). Response categories of partial response (PR), complete resonse (CR), and uncomfirmed (CRu) central review.
Time frame: Up to 2 years
Population: All participants with evaluable data
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MK-8808 Combination Therapy | Clinical Response of Tumor to MK-8808/CVP Combination Therapy | PR | 6 Participants |
| MK-8808 Combination Therapy | Clinical Response of Tumor to MK-8808/CVP Combination Therapy | CR | 0 Participants |
| MK-8808 Combination Therapy | Clinical Response of Tumor to MK-8808/CVP Combination Therapy | CRu | 0 Participants |
Secondary
Cmax of Plasma Levels of MK-8808 During Single Agent Maintenance Therapy
Cmax is a measure of the maximum amount of drug in the plasma over time using samples taken at specified time points.
Time frame: Predose and end of infusion in every other cycle and at end of therapy visit (up to 2 years)
Population: No participants progressed to MK-8808 single agent maintenance therapy; this outcome measure was not assessed.
Secondary
Ctrough of Plasma Levels of MK-8808 When Used as Single Agent Maintenance
Ctrough is a measure of the lowest level of drug in the plasma over time, using plasma samples collected at specified time points.
Time frame: Predose and end of infusion in every other cycle and at end of therapy visit (up to 2 years)
Population: No participants progressed to MK-8808 single agent maintenance therapy; this outcome measure was not assessed.
Secondary
Lowest Concentration (Ctrough) of Plasma Levels of MK-8808 When Used in Combination With CVP
Ctrough is a measure of the lowest level of drug in the plasma over time, using plasma samples collected at specified time points.
Time frame: Pre-dose and end of infusion in each 21-day cycle and at end of therapy visit (up to 24 weeks)
Population: This analysis was not done due to early termination of the study.
Secondary
Maximum Concentration (Cmax) of Plasma Levels of MK-8808 When Used in Combination With CVP
Cmax is a measure of the maximum concentration of the drug in the plasma as measured using plasma samples taken over specified time points.
Time frame: Pre-dose and end of infusion in each 21-day cycle and at end of therapy visit (up to 24 weeks)
Population: This analysis was not done due to early termination of the study.