Back to resultsStudy of MK-8808 for Participants With Follicular Lymphoma (MK-8808-001)
Primary Purpose
Follicular Lymphoma
Status
Terminated
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
MK-8808
cyclophosphamide
vincristine
prednisolone
Sponsored by
About this trial
This is an interventional treatment trial for Follicular Lymphoma
Eligibility Criteria
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:
- is human immunodeficiency virus (HIV)-positive
- is Hepatitis B surface antigen positive (HBsAg+) or is positive for antibodies to Hepatitis B core antigen (anti-HBcAg+)
- has antibodies to Hepatitis C virus
Has one or more of the following:
- Active tuberculosis based on institutional diagnostic criteria and local practice guidelines.
- Evidence of a tuberculosis infection based on a chest X-ray (CXR) or computed tomography (CT) scan performed within 3 months of dosing.
- 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.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
MK-8808 Combination Therapy
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT01370694
First Posted
May 18, 2011
Last Updated
February 28, 2019
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT01370694
Brief Title
Study of MK-8808 for Participants With Follicular Lymphoma (MK-8808-001)
Official Title
An Open-Label, Single Arm Study of MK-8808 in Patients With Advanced CD20-Positive Follicular Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
February 2019
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated for business reasons.
Study Start Date
August 19, 2011 (Actual)
Primary Completion Date
December 1, 2014 (Actual)
Study Completion Date
December 1, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Follicular Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MK-8808 Combination Therapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
MK-8808
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
vincristine
Intervention Type
Drug
Intervention Name(s)
prednisolone
Primary Outcome Measure Information:
Title
Number of Participants Experiencing Clinical and Laboratory Adverse Events (AEs) During MK-8808/CVP Combination Therapy
Description
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
Title
Number of Participants Experiencing Clinical and Laboratory AEs During MK-8808 Maintenance Therapy
Description
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
Secondary Outcome Measure Information:
Title
Maximum Concentration (Cmax) of Plasma Levels of MK-8808 When Used in Combination With CVP
Description
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)
Title
Cmax of Plasma Levels of MK-8808 During Single Agent Maintenance Therapy
Description
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)
Title
Lowest Concentration (Ctrough) of Plasma Levels of MK-8808 When Used in Combination With CVP
Description
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)
Title
Ctrough of Plasma Levels of MK-8808 When Used as Single Agent Maintenance
Description
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)
Title
Clinical Response of Tumor to MK-8808/CVP Combination Therapy
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
is human immunodeficiency virus (HIV)-positive
is Hepatitis B surface antigen positive (HBsAg+) or is positive for antibodies to Hepatitis B core antigen (anti-HBcAg+)
has antibodies to Hepatitis C virus
Has one or more of the following:
Active tuberculosis based on institutional diagnostic criteria and local practice guidelines.
Evidence of a tuberculosis infection based on a chest X-ray (CXR) or computed tomography (CT) scan performed within 3 months of dosing.
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Available IPD and Supporting Information:
Available IPD/Information Type
CSR Synopsis Link
Available IPD/Information URL
http://www.merck.com/clinical-trials/study.html?id=8808-001&kw=8808-001&tab=access
Learn more about this trial
Study of MK-8808 for Participants With Follicular Lymphoma (MK-8808-001)
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