Lymphoma
Conditions
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.
Interventions
DRUGVorinostat
Two 100 mg oral capsules of vorinostat, twice daily (400 mg/day), on Days 1 through 14 of each 21 day cycle
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All participants received the same drug regimen but were allocated to groups based on disease type.
Eligibility
Sex/Gender
ALL
Age
20 Years to 74 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 39 |
| 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. | 11 |
| 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. | 6 |
| Total | 56 |
Baseline characteristics
| Characteristic | Follicular Lymphoma (FL) | Indolent Non-FL B-NHL or MCL | Other Disease | Total |
|---|---|---|---|---|
| Age, Continuous | 57.4 Years STANDARD_DEVIATION 10.4 | 62.9 Years STANDARD_DEVIATION 9.7 | 56.3 Years STANDARD_DEVIATION 10.5 | 58.4 Years STANDARD_DEVIATION 10.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 11 Participants | 6 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 39 Participants | 11 Participants | 6 Participants | 56 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 24 Participants | 4 Participants | 2 Participants | 30 Participants |
| Sex: Female, Male Male | 15 Participants | 7 Participants | 4 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 9 / 39 | 4 / 11 | 3 / 6 |
| other Total, other adverse events | 39 / 39 | 11 / 11 | 6 / 6 |
| serious Total, serious adverse events | 15 / 39 | 4 / 11 | 2 / 6 |
Outcome results
Primary
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.
Time frame: Up to 536 days
Population: All allocated participants who received a dose of study drug were included in this analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Follicular Lymphoma (FL) | Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event (AE) | 6 Participants |
| Indolent Non-FL B-NHL or MCL | Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event (AE) | 1 Participants |
| Other Disease | Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event (AE) | 2 Participants |
Primary
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.
Time frame: Up to approximately 29 months
Population: All allocated participants who received a dose of study drug were included in this analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Follicular Lymphoma (FL) | Number of Participants Who Experienced an Adverse Event (AE) | 39 Participants |
| Indolent Non-FL B-NHL or MCL | Number of Participants Who Experienced an Adverse Event (AE) | 11 Participants |
| Other Disease | Number of Participants Who Experienced an Adverse Event (AE) | 6 Participants |
Primary
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.
Time frame: Up to 650 days
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Follicular Lymphoma (FL) | Objective Response Rate (ORR) | 48.7 Percentage of participants |
| Indolent Non-FL B-NHL or MCL | Objective Response Rate (ORR) | 27.3 Percentage of participants |
Secondary
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.
Time frame: Up to 650 days
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Follicular Lymphoma (FL) | Time to Response for Relapsed/Refractory FL | NA Days |
Secondary
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 frame: Up to 650 days
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Follicular Lymphoma (FL) | Time to Treatment Failure for Relapsed/Refractory FL | 323 Days |