Back to resultsStudy 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)
Primary Purpose
Lymphoma
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Vorinostat
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Follicular Lymphoma (FL)
Indolent non-FL B-NHL or MCL
Other Disease
Arm 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.
Outcomes
Primary Outcome Measures
Objective Response Rate (ORR)
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)
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)
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
Time to Treatment Failure for Relapsed/Refractory FL
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 FL
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00875056
Brief Title
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)
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)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
April 15, 2009 (Actual)
Primary Completion Date
September 6, 2011 (Actual)
Study Completion Date
February 8, 2019 (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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
All participants received the same drug regimen but were allocated to groups based on disease type.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
56 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Follicular Lymphoma (FL)
Arm Type
Experimental
Arm 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.
Arm Title
Indolent non-FL B-NHL or MCL
Arm Type
Experimental
Arm Description
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.
Arm Title
Other Disease
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Vorinostat
Other Intervention Name(s)
MK-0683, Zolinza
Intervention Description
Two 100 mg oral capsules of vorinostat, twice daily (400 mg/day), on Days 1 through 14 of each 21 day cycle
Primary Outcome Measure Information:
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
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
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
Secondary Outcome Measure Information:
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
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
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
Citations:
PubMed Identifier
24617454
Citation
Ogura M, Ando K, Suzuki T, Ishizawa K, Oh SY, Itoh K, Yamamoto K, Au WY, Tien HF, Matsuno Y, Terauchi T, Yamamoto K, Mori M, Tanaka Y, Shimamoto T, Tobinai K, Kim WS. A multicentre phase II study of vorinostat in patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma. Br J Haematol. 2014 Jun;165(6):768-76. doi: 10.1111/bjh.12819. Epub 2014 Mar 12.
Results Reference
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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)
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