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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)

Phase 2
Completed
Conditions
Lymphoma
Interventions
Registration Number
NCT00875056
Lead Sponsor
Merck Sharp & Dohme LLC
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
56
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Indolent non-FL B-NHL or MCLVorinostatParticipants 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.
Follicular Lymphoma (FL)VorinostatParticipants 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.
Other DiseaseVorinostatParticipants 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.
Primary Outcome Measures
NameTimeMethod
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.

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.

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
NameTimeMethod
Time to Treatment Failure for Relapsed/Refractory FLUp 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.

Time to Response for Relapsed/Refractory FLUp 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.

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