Study of Vorinostat (MK-0683) With Follicular Lymphoma (FL), Other Indolent B-cell Non-Hodgkin's Lymphoma (B-NHL), or Mantle Cell Lymphoma (MCL) Participants (MK-0683-103)

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT00875056
Collaborator
(none)
56
3
117.8

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and efficacy of vorinostat (MK-0683) in participants with relapsed and/or refractory follicular lymphoma. The exploratory purpose of this study is to evaluate efficacy of MK-0683 in participants with relapsed/refractory non-FL indolent B-NHL or relapsed/refractory MCL. The primary hypothesis is that MK-0683 will show efficacy in relapsed/refractory FL patients as measured by the Overall Response Rate.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
56 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
All participants received the same drug regimen but were allocated to groups based on disease type.All participants received the same drug regimen but were allocated to groups based on disease type.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Study of MK-0683 in Patients With Relapsed / Refractory Follicular Lymphoma (FL), Other Indolent B-cell Non-Hodgkin's Lymphoma (B-NHL) or Mantle Cell Lymphoma (MCL)
Actual Study Start Date :
Apr 15, 2009
Actual Primary Completion Date :
Sep 6, 2011
Actual Study Completion Date :
Feb 8, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Follicular Lymphoma (FL)

Participants with relapsed/refractory FL received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol.

Drug: Vorinostat
Two 100 mg oral capsules of vorinostat, twice daily (400 mg/day), on Days 1 through 14 of each 21 day cycle
Other Names:
  • MK-0683
  • Zolinza
  • Experimental: Indolent non-FL B-NHL or MCL

    Participants with indolent non-follicular lymphoma (FL) B-cell non-Hodgkin's lymphoma (B-NHL), or with mantle cell Lymphoma (MCL) received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol.

    Drug: Vorinostat
    Two 100 mg oral capsules of vorinostat, twice daily (400 mg/day), on Days 1 through 14 of each 21 day cycle
    Other Names:
  • MK-0683
  • Zolinza
  • Experimental: Other Disease

    Participants with disease other than relapsed/refractory follicular lymphoma (FL), non-FL B-cell non-Hodgkin's lymphoma (B-NHL), or mantle cell Lymphoma (MCL), as assessed by the Independent Central Pathological Committee, received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. This group was created to include participants who enrolled, but whose later diagnoses by the Independent Central Pathological Committee excluded them from analysis in the FL and non-FL B-NHL/MCL groups because they had different disease than those prespecified in the protocol.

    Drug: Vorinostat
    Two 100 mg oral capsules of vorinostat, twice daily (400 mg/day), on Days 1 through 14 of each 21 day cycle
    Other Names:
  • MK-0683
  • Zolinza
  • Outcome Measures

    Primary Outcome Measures

    1. Objective Response Rate (ORR) [Up to 650 days]

      ORR was defined as the percentage of participants who had a Complete Response (CR: Normal liver/spleen physical exam, all lymph nodes and nodal masses are normal, and there is no bone marrow involvement), a Complete Response/unconfirmed (CRu: Normal liver/spleen physical exam, plus at least a 75% decrease in the sum of the products of the greatest diameters of nodal masses if any are greater than 1.5 cm in their greatest diameter, normal or indeterminate bone marrow involvement), or a Partial Response (PR: Either normal physical exam, lymph nodes, and lymph node masses plus positive bone marrow involvement; OR normal physical exam or decrease in liver/spleen size plus at least a 50% decrease in the diameters of lymph nodes and nodal masses) as assessed using the international working group Non-Hodgkin's lymphoma standardized response criteria described by Cheson, BD in 1999. The percentage of participants who experienced a CR, CRu, or PR is presented.

    2. Number of Participants Who Experienced an Adverse Event (AE) [Up to approximately 29 months]

      An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE was presented.

    3. Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event (AE) [Up to 536 days]

      An adverse event (AE) was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued from study drug due to an adverse event was reported.

    Secondary Outcome Measures

    1. Time to Treatment Failure for Relapsed/Refractory FL [Up to 650 days]

      Time to Treatment Failure is defined as the time from allocation until the date of any treatment failure, including documented disease progression, or discontinuation of the study medication for any reason. Data was censored on the efficacy data cutoff date of 25 February, 2011.

    2. Time to Response for Relapsed/Refractory FL [Up to 650 days]

      Time to Response is defined as the time from allocation until the time of an initial response. Data was censored on the efficacy data cutoff date of 25 February, 2011.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    20 Years to 74 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Participant has an histopathologically confirmed follicular lymphoma (FL), or other indolent B-cell non-Hodgkin's lymphoma (B-NHL) or mantle cell lymphoma (MCL)

    • Only relapsed/refractory FL can be included outside Japan

    • Participant has at least one measurable lesion by computerized tomography (CT) scan which is defined by Cheson's 1999 criteria

    • Participant has received at least 1 but up to 4 prior chemotherapeutic regimens, the most recent therapy must have failed to induce a partial response, or there must be recurrence in case of the most recent therapy has shown complete response, or there must be relapse in case of the most recent therapy has shown partial response

    • Life expectancy of >4 months

    • Participant must have adequate organ and marrow function

    • Women of child bearing potential must be negative for pregnancy and agree to use effective contraceptive measures until 30 days after the last dose of MK-0683.

    • Men must agree to use effective contraceptive measures until 6 months after the last dose of MK-0683

    Exclusion Criteria:
    • Participant has undergone allogenic transplant treatment or autologous stem cell transplant within 6 months

    • Participant with other active malignancies or central neurological infiltration with lymphoma

    • Participant with severe hepatic insufficiency

    • Participant with history of allergic reactions attributed to any component of MK-0683

    • Participant is known to be human immunodeficiency virus (HIV) antibody-, hepatitis B virus antigen- or hepatitis C virus antibody-positive

    • Participant has undergone prior/concomitant treatment with MK-0683 or other histone deacetylase (HDAC) inhibitors

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Merck Sharp & Dohme LLC

    Investigators

    • Study Director: Medical Director, Merck Sharp & Dohme LLC

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT00875056
    Other Study ID Numbers:
    • 0683-103
    • 2009_570
    • 132248
    • MK-0683-103
    First Posted:
    Apr 3, 2009
    Last Update Posted:
    Oct 29, 2020
    Last Verified:
    Oct 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Follicular Lymphoma (FL) Indolent Non-FL B-NHL or MCL Other Disease
    Arm/Group Description Participants with relapsed/refractory FL received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. Participants with indolent non-follicular lymphoma (FL) B-cell non-Hodgkin's lymphoma (B-NHL), or with mantle cell Lymphoma (MCL) received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. Participants with disease other than relapsed/refractory follicular lymphoma (FL), non-FL B-cell non-Hodgkin's lymphoma (B-NHL), or mantle cell Lymphoma (MCL), as assessed by the Independent Central Pathological Committee, received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. This group was created to include participants who enrolled, but whose later diagnoses by the Independent Central Pathological Committee excluded them from analysis in the FL and non-FL B-NHL/MCL groups because they had different disease than those prespecified in the protocol.
    Period Title: Overall Study
    STARTED 39 11 6
    COMPLETED 16 2 0
    NOT COMPLETED 23 9 6

    Baseline Characteristics

    Arm/Group Title Follicular Lymphoma (FL) Indolent Non-FL B-NHL or MCL Other Disease Total
    Arm/Group Description Participants with relapsed/refractory FL received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. Participants with indolent non-follicular lymphoma (FL) B-cell non-Hodgkin's lymphoma (B-NHL), or with mantle cell Lymphoma (MCL) received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. Participants with disease other than relapsed/refractory follicular lymphoma (FL), non-FL B-cell non-Hodgkin's lymphoma (B-NHL), or mantle cell Lymphoma (MCL), as assessed by the Independent Central Pathological Committee, received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. This group was created to include participants who enrolled, but whose later diagnoses by the Independent Central Pathological Committee excluded them from analysis in the FL and non-FL B-NHL/MCL groups because they had different disease than those prespecified in the protocol. Total of all reporting groups
    Overall Participants 39 11 6 56
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    57.4
    (10.4)
    62.9
    (9.7)
    56.3
    (10.5)
    58.4
    (10.4)
    Sex: Female, Male (Count of Participants)
    Female
    24
    61.5%
    4
    36.4%
    2
    33.3%
    30
    53.6%
    Male
    15
    38.5%
    7
    63.6%
    4
    66.7%
    26
    46.4%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    39
    100%
    11
    100%
    6
    100%
    56
    100%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    39
    100%
    11
    100%
    6
    100%
    56
    100%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Objective Response Rate (ORR)
    Description ORR was defined as the percentage of participants who had a Complete Response (CR: Normal liver/spleen physical exam, all lymph nodes and nodal masses are normal, and there is no bone marrow involvement), a Complete Response/unconfirmed (CRu: Normal liver/spleen physical exam, plus at least a 75% decrease in the sum of the products of the greatest diameters of nodal masses if any are greater than 1.5 cm in their greatest diameter, normal or indeterminate bone marrow involvement), or a Partial Response (PR: Either normal physical exam, lymph nodes, and lymph node masses plus positive bone marrow involvement; OR normal physical exam or decrease in liver/spleen size plus at least a 50% decrease in the diameters of lymph nodes and nodal masses) as assessed using the international working group Non-Hodgkin's lymphoma standardized response criteria described by Cheson, BD in 1999. The percentage of participants who experienced a CR, CRu, or PR is presented.
    Time Frame Up to 650 days

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all allocated participants with follicular lymphoma (FL), non-FL B cell non-Hodgkin's lymphoma (B-NHL), or mantle cell lymphoma (MCL) who received at least one dose of study drug, and had some post-allocation endpoint data.
    Arm/Group Title Follicular Lymphoma (FL) Indolent Non-FL B-NHL or MCL Other Disease
    Arm/Group Description Participants with relapsed/refractory FL received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. Participants with indolent non-follicular lymphoma (FL) B-cell non-Hodgkin's lymphoma (B-NHL), or with mantle cell Lymphoma (MCL) received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. Participants with disease other than relapsed/refractory follicular lymphoma (FL), non-FL B-cell non-Hodgkin's lymphoma (B-NHL), or mantle cell Lymphoma (MCL), as assessed by the Independent Central Pathological Committee, received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. This group was created to include participants who enrolled, but whose later diagnoses by the Independent Central Pathological Committee excluded them from analysis in the FL and non-FL B-NHL/MCL groups because they had different disease than those prespecified in the protocol.
    Measure Participants 39 11 0
    Number (95% Confidence Interval) [Percentage of participants]
    48.7
    124.9%
    27.3
    248.2%
    2. Primary Outcome
    Title Number of Participants Who Experienced an Adverse Event (AE)
    Description An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE was presented.
    Time Frame Up to approximately 29 months

    Outcome Measure Data

    Analysis Population Description
    All allocated participants who received a dose of study drug were included in this analysis.
    Arm/Group Title Follicular Lymphoma (FL) Indolent Non-FL B-NHL or MCL Other Disease
    Arm/Group Description Participants with relapsed/refractory FL received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. Participants with indolent non-follicular lymphoma (FL) B-cell non-Hodgkin's lymphoma (B-NHL), or with mantle cell Lymphoma (MCL) received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. Participants with disease other than relapsed/refractory follicular lymphoma (FL), non-FL B-cell non-Hodgkin's lymphoma (B-NHL), or mantle cell Lymphoma (MCL), as assessed by the Independent Central Pathological Committee, received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. This group was created to include participants who enrolled, but whose later diagnoses by the Independent Central Pathological Committee excluded them from analysis in the FL and non-FL B-NHL/MCL groups because they had different disease than those prespecified in the protocol.
    Measure Participants 39 11 6
    Count of Participants [Participants]
    39
    100%
    11
    100%
    6
    100%
    3. Secondary Outcome
    Title Time to Treatment Failure for Relapsed/Refractory FL
    Description Time to Treatment Failure is defined as the time from allocation until the date of any treatment failure, including documented disease progression, or discontinuation of the study medication for any reason. Data was censored on the efficacy data cutoff date of 25 February, 2011.
    Time Frame Up to 650 days

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all allocated participants with FL who received at least one dose of study drug, and had some post-allocation endpoint data.
    Arm/Group Title Follicular Lymphoma (FL) Indolent Non-FL B-NHL or MCL Other Disease
    Arm/Group Description Participants with relapsed/refractory FL received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. Participants with indolent non-follicular lymphoma (FL) B-cell non-Hodgkin's lymphoma (B-NHL), or with mantle cell Lymphoma (MCL) received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. Participants with disease other than relapsed/refractory follicular lymphoma (FL), non-FL B-cell non-Hodgkin's lymphoma (B-NHL), or mantle cell Lymphoma (MCL), as assessed by the Independent Central Pathological Committee, received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. This group was created to include participants who enrolled, but whose later diagnoses by the Independent Central Pathological Committee excluded them from analysis in the FL and non-FL B-NHL/MCL groups because they had different disease than those prespecified in the protocol.
    Measure Participants 39 0 0
    Median (Full Range) [Days]
    323
    4. Secondary Outcome
    Title Time to Response for Relapsed/Refractory FL
    Description Time to Response is defined as the time from allocation until the time of an initial response. Data was censored on the efficacy data cutoff date of 25 February, 2011.
    Time Frame Up to 650 days

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all allocated participants with FL who received at least one dose of study drug, and had some post-allocation endpoint data.
    Arm/Group Title Follicular Lymphoma (FL) Indolent Non-FL B-NHL or MCL Other Disease
    Arm/Group Description Participants with relapsed/refractory FL received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. Participants with indolent non-follicular lymphoma (FL) B-cell non-Hodgkin's lymphoma (B-NHL), or with mantle cell Lymphoma (MCL) received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. Participants with disease other than relapsed/refractory follicular lymphoma (FL), non-FL B-cell non-Hodgkin's lymphoma (B-NHL), or mantle cell Lymphoma (MCL), as assessed by the Independent Central Pathological Committee, received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. This group was created to include participants who enrolled, but whose later diagnoses by the Independent Central Pathological Committee excluded them from analysis in the FL and non-FL B-NHL/MCL groups because they had different disease than those prespecified in the protocol.
    Measure Participants 39 0 0
    Median (Full Range) [Days]
    NA
    5. Primary Outcome
    Title Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event (AE)
    Description An adverse event (AE) was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued from study drug due to an adverse event was reported.
    Time Frame Up to 536 days

    Outcome Measure Data

    Analysis Population Description
    All allocated participants who received a dose of study drug were included in this analysis.
    Arm/Group Title Follicular Lymphoma (FL) Indolent Non-FL B-NHL or MCL Other Disease
    Arm/Group Description Participants with relapsed/refractory FL received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. Participants with indolent non-follicular lymphoma (FL) B-cell non-Hodgkin's lymphoma (B-NHL), or with mantle cell Lymphoma (MCL) received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. Participants with disease other than relapsed/refractory follicular lymphoma (FL), non-FL B-cell non-Hodgkin's lymphoma (B-NHL), or mantle cell Lymphoma (MCL), as assessed by the Independent Central Pathological Committee, received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. This group was created to include participants who enrolled, but whose later diagnoses by the Independent Central Pathological Committee excluded them from analysis in the FL and non-FL B-NHL/MCL groups because they had different disease than those prespecified in the protocol.
    Measure Participants 39 11 6
    Count of Participants [Participants]
    6
    15.4%
    1
    9.1%
    2
    33.3%

    Adverse Events

    Time Frame Up to approximately 29 months
    Adverse Event Reporting Description Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.
    Arm/Group Title Follicular Lymphoma (FL) Indolent Non-FL B-NHL or MCL Other Disease
    Arm/Group Description Participants with relapsed/refractory FL received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. Participants with indolent non-follicular lymphoma (FL) B-cell non-Hodgkin's lymphoma (B-NHL), or with mantle cell Lymphoma (MCL) received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. Participants with disease other than relapsed/refractory follicular lymphoma (FL), non-FL B-cell non-Hodgkin's lymphoma (B-NHL), or mantle cell Lymphoma (MCL), as assessed by the Independent Central Pathological Committee, received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. This group was created to include participants who enrolled, but whose later diagnoses by the Independent Central Pathological Committee excluded them from analysis in the FL and non-FL B-NHL/MCL groups because they had different disease than those prespecified in the protocol.
    All Cause Mortality
    Follicular Lymphoma (FL) Indolent Non-FL B-NHL or MCL Other Disease
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/39 (10.3%) 3/11 (27.3%) 2/6 (33.3%)
    Serious Adverse Events
    Follicular Lymphoma (FL) Indolent Non-FL B-NHL or MCL Other Disease
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 9/39 (23.1%) 3/11 (27.3%) 2/6 (33.3%)
    Blood and lymphatic system disorders
    Neutropenia 0/39 (0%) 0 1/11 (9.1%) 1 0/6 (0%) 0
    Thrombocytopenia 2/39 (5.1%) 2 1/11 (9.1%) 1 0/6 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 1/39 (2.6%) 1 0/11 (0%) 0 0/6 (0%) 0
    General disorders
    Asthenia 1/39 (2.6%) 1 0/11 (0%) 0 0/6 (0%) 0
    Infections and infestations
    H1N1 influenza 1/39 (2.6%) 1 0/11 (0%) 0 0/6 (0%) 0
    Meningitis aseptic 1/39 (2.6%) 1 0/11 (0%) 0 0/6 (0%) 0
    Pneumonia 0/39 (0%) 0 1/11 (9.1%) 1 0/6 (0%) 0
    Injury, poisoning and procedural complications
    Muscle injury 1/39 (2.6%) 1 0/11 (0%) 0 0/6 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite 2/39 (5.1%) 2 0/11 (0%) 0 0/6 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer 0/39 (0%) 0 0/11 (0%) 0 1/6 (16.7%) 1
    Nervous system disorders
    Dizziness 1/39 (2.6%) 1 0/11 (0%) 0 0/6 (0%) 0
    VIth nerve paralysis 0/39 (0%) 0 0/11 (0%) 0 1/6 (16.7%) 1
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion 1/39 (2.6%) 1 0/11 (0%) 0 0/6 (0%) 0
    Pleural haemorrhage 0/39 (0%) 0 1/11 (9.1%) 1 0/6 (0%) 0
    Vascular disorders
    Deep vein thrombosis 1/39 (2.6%) 1 0/11 (0%) 0 0/6 (0%) 0
    Embolism venous 1/39 (2.6%) 1 0/11 (0%) 0 0/6 (0%) 0
    Other (Not Including Serious) Adverse Events
    Follicular Lymphoma (FL) Indolent Non-FL B-NHL or MCL Other Disease
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 39/39 (100%) 11/11 (100%) 6/6 (100%)
    Blood and lymphatic system disorders
    Anaemia 13/39 (33.3%) 24 5/11 (45.5%) 11 1/6 (16.7%) 1
    Erythropenia 0/39 (0%) 0 1/11 (9.1%) 3 0/6 (0%) 0
    Leukopenia 20/39 (51.3%) 93 8/11 (72.7%) 42 3/6 (50%) 11
    Lymphadenitis 1/39 (2.6%) 1 0/11 (0%) 0 1/6 (16.7%) 1
    Lymphopenia 13/39 (33.3%) 36 6/11 (54.5%) 17 0/6 (0%) 0
    Neutropenia 28/39 (71.8%) 138 7/11 (63.6%) 61 2/6 (33.3%) 7
    Thrombocytopenia 37/39 (94.9%) 171 10/11 (90.9%) 56 5/6 (83.3%) 15
    Cardiac disorders
    Palpitations 4/39 (10.3%) 5 0/11 (0%) 0 0/6 (0%) 0
    Supraventricular extrasystoles 0/39 (0%) 0 1/11 (9.1%) 1 0/6 (0%) 0
    Ear and labyrinth disorders
    Tinnitus 2/39 (5.1%) 2 0/11 (0%) 0 0/6 (0%) 0
    Eye disorders
    Conjunctivitis 2/39 (5.1%) 2 0/11 (0%) 0 0/6 (0%) 0
    Gastrointestinal disorders
    Abdominal discomfort 3/39 (7.7%) 8 1/11 (9.1%) 1 0/6 (0%) 0
    Abdominal distension 3/39 (7.7%) 8 1/11 (9.1%) 1 0/6 (0%) 0
    Abdominal pain 6/39 (15.4%) 7 0/11 (0%) 0 0/6 (0%) 0
    Abdominal pain upper 5/39 (12.8%) 7 1/11 (9.1%) 1 0/6 (0%) 0
    Cheilitis 3/39 (7.7%) 7 2/11 (18.2%) 2 0/6 (0%) 0
    Constipation 15/39 (38.5%) 30 3/11 (27.3%) 7 1/6 (16.7%) 1
    Dental caries 2/39 (5.1%) 2 0/11 (0%) 0 0/6 (0%) 0
    Diarrhoea 28/39 (71.8%) 247 9/11 (81.8%) 89 5/6 (83.3%) 15
    Dry mouth 4/39 (10.3%) 10 1/11 (9.1%) 3 0/6 (0%) 0
    Dyspepsia 3/39 (7.7%) 5 2/11 (18.2%) 2 0/6 (0%) 0
    Enterocolitis 0/39 (0%) 0 1/11 (9.1%) 1 0/6 (0%) 0
    Flatulence 2/39 (5.1%) 3 0/11 (0%) 0 0/6 (0%) 0
    Gastritis 4/39 (10.3%) 4 0/11 (0%) 0 0/6 (0%) 0
    Glossodynia 0/39 (0%) 0 1/11 (9.1%) 1 0/6 (0%) 0
    Haemorrhoids 1/39 (2.6%) 1 1/11 (9.1%) 1 0/6 (0%) 0
    Nausea 24/39 (61.5%) 89 7/11 (63.6%) 12 3/6 (50%) 4
    Stomatitis 9/39 (23.1%) 24 1/11 (9.1%) 1 0/6 (0%) 0
    Vomiting 13/39 (33.3%) 47 1/11 (9.1%) 1 2/6 (33.3%) 4
    General disorders
    Asthenia 6/39 (15.4%) 18 1/11 (9.1%) 1 0/6 (0%) 0
    Chest discomfort 0/39 (0%) 0 1/11 (9.1%) 1 0/6 (0%) 0
    Chest pain 4/39 (10.3%) 4 0/11 (0%) 0 0/6 (0%) 0
    Chills 2/39 (5.1%) 4 0/11 (0%) 0 1/6 (16.7%) 1
    Face oedema 0/39 (0%) 0 1/11 (9.1%) 1 0/6 (0%) 0
    Facial pain 0/39 (0%) 0 1/11 (9.1%) 1 0/6 (0%) 0
    Fatigue 22/39 (56.4%) 90 5/11 (45.5%) 14 2/6 (33.3%) 4
    Influenza like illness 0/39 (0%) 0 1/11 (9.1%) 1 0/6 (0%) 0
    Mucosal inflammation 3/39 (7.7%) 3 0/11 (0%) 0 0/6 (0%) 0
    Oedema 1/39 (2.6%) 1 1/11 (9.1%) 1 1/6 (16.7%) 1
    Oedema peripheral 3/39 (7.7%) 3 1/11 (9.1%) 2 0/6 (0%) 0
    Puncture site pain 0/39 (0%) 0 1/11 (9.1%) 1 0/6 (0%) 0
    Pyrexia 4/39 (10.3%) 4 0/11 (0%) 0 0/6 (0%) 0
    Hepatobiliary disorders
    Hyperbilirubinaemia 10/39 (25.6%) 34 3/11 (27.3%) 10 1/6 (16.7%) 1
    Immune system disorders
    Hypersensitivity 0/39 (0%) 0 1/11 (9.1%) 2 0/6 (0%) 0
    Infections and infestations
    Influenza 3/39 (7.7%) 3 0/11 (0%) 0 0/6 (0%) 0
    Nasopharyngitis 17/39 (43.6%) 37 4/11 (36.4%) 9 1/6 (16.7%) 1
    Oral herpes 0/39 (0%) 0 1/11 (9.1%) 1 0/6 (0%) 0
    Pharyngitis 2/39 (5.1%) 2 0/11 (0%) 0 0/6 (0%) 0
    Upper aerodigestive tract infection 0/39 (0%) 0 0/11 (0%) 0 1/6 (16.7%) 1
    Upper respiratory tract infection 6/39 (15.4%) 11 0/11 (0%) 0 0/6 (0%) 0
    Injury, poisoning and procedural complications
    Accidental overdose 9/39 (23.1%) 9 1/11 (9.1%) 1 0/6 (0%) 0
    Animal bite 4/39 (10.3%) 4 0/11 (0%) 0 0/6 (0%) 0
    Investigations
    Alanine aminotransferase increased 9/39 (23.1%) 20 1/11 (9.1%) 1 1/6 (16.7%) 2
    Aspartate aminotransferase increased 10/39 (25.6%) 21 4/11 (36.4%) 7 1/6 (16.7%) 2
    Blood bilirubin increased 3/39 (7.7%) 6 1/11 (9.1%) 3 0/6 (0%) 0
    Blood creatine phosphokinase increased 1/39 (2.6%) 1 0/11 (0%) 0 1/6 (16.7%) 1
    Blood creatinine increased 9/39 (23.1%) 39 2/11 (18.2%) 7 2/6 (33.3%) 7
    Blood lactate dehydrogenase increased 5/39 (12.8%) 9 2/11 (18.2%) 13 2/6 (33.3%) 7
    Blood phosphorus decreased 0/39 (0%) 0 1/11 (9.1%) 2 0/6 (0%) 0
    Blood urea increased 4/39 (10.3%) 9 1/11 (9.1%) 2 0/6 (0%) 0
    Weight decreased 11/39 (28.2%) 11 3/11 (27.3%) 3 1/6 (16.7%) 1
    Metabolism and nutrition disorders
    Decreased appetite 26/39 (66.7%) 120 6/11 (54.5%) 15 3/6 (50%) 3
    Dehydration 3/39 (7.7%) 15 0/11 (0%) 0 0/6 (0%) 0
    Hypercreatininaemia 7/39 (17.9%) 22 2/11 (18.2%) 8 1/6 (16.7%) 2
    Hyperglycaemia 9/39 (23.1%) 20 4/11 (36.4%) 7 0/6 (0%) 0
    Hyperkalaemia 3/39 (7.7%) 13 3/11 (27.3%) 12 0/6 (0%) 0
    Hypermagnesaemia 5/39 (12.8%) 22 0/11 (0%) 0 0/6 (0%) 0
    Hyperphosphataemia 0/39 (0%) 0 1/11 (9.1%) 1 1/6 (16.7%) 1
    Hyperphosphatasaemia 2/39 (5.1%) 3 0/11 (0%) 0 0/6 (0%) 0
    Hypoalbuminaemia 4/39 (10.3%) 24 1/11 (9.1%) 1 0/6 (0%) 0
    Hypocalcaemia 4/39 (10.3%) 14 0/11 (0%) 0 0/6 (0%) 0
    Hypokalaemia 3/39 (7.7%) 11 0/11 (0%) 0 0/6 (0%) 0
    Hyponatraemia 3/39 (7.7%) 6 1/11 (9.1%) 1 0/6 (0%) 0
    Hypophosphataemia 10/39 (25.6%) 32 1/11 (9.1%) 10 1/6 (16.7%) 1
    Hypoproteinaemia 2/39 (5.1%) 7 1/11 (9.1%) 1 0/6 (0%) 0
    Musculoskeletal and connective tissue disorders
    Back pain 3/39 (7.7%) 3 1/11 (9.1%) 2 0/6 (0%) 0
    Muscle spasms 3/39 (7.7%) 5 1/11 (9.1%) 1 0/6 (0%) 0
    Myositis 1/39 (2.6%) 1 0/11 (0%) 0 1/6 (16.7%) 1
    Pain in extremity 3/39 (7.7%) 5 0/11 (0%) 0 0/6 (0%) 0
    Nervous system disorders
    Dizziness 3/39 (7.7%) 3 0/11 (0%) 0 0/6 (0%) 0
    Dysgeusia 14/39 (35.9%) 66 3/11 (27.3%) 5 3/6 (50%) 3
    Headache 7/39 (17.9%) 12 1/11 (9.1%) 1 0/6 (0%) 0
    Hyperaesthesia 1/39 (2.6%) 2 0/11 (0%) 0 1/6 (16.7%) 1
    Hypoaesthesia 3/39 (7.7%) 3 0/11 (0%) 0 0/6 (0%) 0
    Neuropathy peripheral 2/39 (5.1%) 2 0/11 (0%) 0 1/6 (16.7%) 1
    Peripheral sensory neuropathy 3/39 (7.7%) 5 0/11 (0%) 0 0/6 (0%) 0
    Somnolence 2/39 (5.1%) 4 1/11 (9.1%) 2 0/6 (0%) 0
    Psychiatric disorders
    Anxiety 2/39 (5.1%) 2 0/11 (0%) 0 0/6 (0%) 0
    Depression 0/39 (0%) 0 1/11 (9.1%) 1 0/6 (0%) 0
    Insomnia 2/39 (5.1%) 3 1/11 (9.1%) 1 1/6 (16.7%) 1
    Renal and urinary disorders
    Haematuria 1/39 (2.6%) 1 1/11 (9.1%) 1 1/6 (16.7%) 2
    Proteinuria 6/39 (15.4%) 13 2/11 (18.2%) 4 1/6 (16.7%) 1
    Respiratory, thoracic and mediastinal disorders
    Cough 5/39 (12.8%) 8 1/11 (9.1%) 1 0/6 (0%) 0
    Dysphonia 1/39 (2.6%) 1 0/11 (0%) 0 1/6 (16.7%) 1
    Dyspnoea 2/39 (5.1%) 2 1/11 (9.1%) 2 0/6 (0%) 0
    Oropharyngeal pain 5/39 (12.8%) 7 1/11 (9.1%) 1 1/6 (16.7%) 1
    Productive cough 1/39 (2.6%) 1 1/11 (9.1%) 1 0/6 (0%) 0
    Rhinorrhoea 4/39 (10.3%) 10 0/11 (0%) 0 0/6 (0%) 0
    Upper respiratory tract inflammation 6/39 (15.4%) 13 1/11 (9.1%) 4 1/6 (16.7%) 1
    Skin and subcutaneous tissue disorders
    Alopecia 20/39 (51.3%) 20 4/11 (36.4%) 4 2/6 (33.3%) 2
    Asteatosis 0/39 (0%) 0 1/11 (9.1%) 1 0/6 (0%) 0
    Dermatitis acneiform 0/39 (0%) 0 0/11 (0%) 0 1/6 (16.7%) 1
    Erythema nodosum 0/39 (0%) 0 1/11 (9.1%) 1 0/6 (0%) 0
    Haemorrhage subcutaneous 2/39 (5.1%) 2 0/11 (0%) 0 0/6 (0%) 0
    Nail disorder 8/39 (20.5%) 8 1/11 (9.1%) 1 1/6 (16.7%) 1
    Night sweats 3/39 (7.7%) 3 0/11 (0%) 0 0/6 (0%) 0
    Photosensitivity reaction 0/39 (0%) 0 0/11 (0%) 0 1/6 (16.7%) 1
    Pruritus 1/39 (2.6%) 3 1/11 (9.1%) 1 0/6 (0%) 0
    Rash 8/39 (20.5%) 11 2/11 (18.2%) 2 0/6 (0%) 0
    Skin exfoliation 1/39 (2.6%) 1 1/11 (9.1%) 1 0/6 (0%) 0
    Vascular disorders
    Hot flush 2/39 (5.1%) 2 0/11 (0%) 0 0/6 (0%) 0
    Hypertension 2/39 (5.1%) 2 1/11 (9.1%) 1 0/6 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication guidelines.

    Results Point of Contact

    Name/Title Senior Vice President, Global Clinical Development
    Organization Merck Sharp & Dohme Corp.
    Phone 1-800-672-6372
    Email ClinicalTrialsDisclosure@merck.com
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT00875056
    Other Study ID Numbers:
    • 0683-103
    • 2009_570
    • 132248
    • MK-0683-103
    First Posted:
    Apr 3, 2009
    Last Update Posted:
    Oct 29, 2020
    Last Verified:
    Oct 1, 2020