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Study of MK-8808 for Participants With Follicular Lymphoma (MK-8808-001)

This study has been terminated.
(The study was terminated for business reasons.)
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01370694
First received: May 18, 2011
Last updated: April 25, 2016
Last verified: April 2016
  Purpose
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.

Condition Intervention Phase
Follicular Lymphoma
Drug: MK-8808
Drug: cyclophosphamide
Drug: vincristine
Drug: prednisolone
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Single Arm Study of MK-8808 in Patients With Advanced CD20-Positive Follicular Lymphoma

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Number of Participants Experiencing Clinical and Laboratory Adverse Events (AEs) During MK-8808/CVP Combination Therapy [ Time Frame: From first dose of combination therapy up to 24 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: From first dose of single agent MK-8808 up to 2 years ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Pre-dose and end of infusion in each 21-day cycle and at end of therapy visit (up to 24 weeks) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Predose and end of infusion in every other cycle and at end of therapy visit (up to 2 years) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Pre-dose and end of infusion in each 21-day cycle and at end of therapy visit (up to 24 weeks) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Predose and end of infusion in every other cycle and at end of therapy visit (up to 2 years) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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.


Enrollment: 7
Study Start Date: August 2011
Study Completion Date: December 2014
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: MK-8808 Drug: cyclophosphamide Drug: vincristine Drug: prednisolone

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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:

    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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01370694

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01370694     History of Changes
Other Study ID Numbers: 8808-001  2011-000386-13 
Study First Received: May 18, 2011
Results First Received: October 23, 2015
Last Updated: April 25, 2016
Health Authority: Russia: Ministry of Health of the Russian Federation

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Vincristine
Prednisolone
Methylprednisolone Hemisuccinate
Prednisolone acetate
Methylprednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents

ClinicalTrials.gov processed this record on December 05, 2016