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Vorinostat (MK-0683, SAHA [Suberoylanilide Hydroxamic Acid]) + Lenalidomide + Dexamethasone in Multiple Myeloma (MM) (MK-0683-074)

Primary Purpose

Relapsed or Refractory Multiple Myeloma

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Vorinostat
Lenalidomide
Dexamethasone
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed or Refractory Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Is a male or female at least 18 years old
  • Has relapsed or refractory MM and has had at least one prior therapy
  • Female participants of childbearing potential must have 2 negative serum pregnancy tests prior to receiving the first dose of study drugs
  • Female participants who can become pregnant must agree to use 2 separate forms of effective birth control at the same time, 4 weeks before, while taking, and for 4 weeks after stopping lenalidomide; post menopausal participants should be free from menses for >2 years, or are surgically sterilized
  • Male participant agrees to use an adequate method of contraception for the duration of the study, even if the participant has undergone a successful vasectomy
  • Male participants must agree to use a latex condom during sexual contact with a pregnant female or a female who can become pregnant; this is required for the duration of the study, and for 4 weeks after stopping therapy
  • Has at least 3 weeks washout prior to treatment
  • Is able to swallow capsules and is able to take or tolerate oral medications on a continuous basis

Exclusion Criteria:

  • Has prior treatment with a histone deacetylase (HDAC) inhibitor
  • Has prior allogenetic bone marrow transplant
  • Has received intravenous antibiotics, antiviral, or antifungal agents within 2 weeks prior to the start of the study drug
  • Uses illicit drugs, substance abuse or had a recent history (within the last year) of drug or alcohol abuse
  • Is pregnant or breast feeding or expecting to have a baby during the course of the study
  • Has human immunodeficiency virus (HIV) infection
  • Has Hepatitis B/C infection
  • Is currently receiving treatment for another type of cancer other than skin or cervical cancer that has not been in remission for 5 years or longer

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    Level 1: Vorinostat 300 mg + lenalidomide 10 mg

    Level 2: Vorinostat 400 mg + lenalidomide 10 mg

    Level 3: Vorinostat 400 mg + lenalidomide 15 mg

    Level 4: Vorinostat 400 mg + lenalidomide 20 mg

    Level 5: Vorinostat 400 mg + lenalidomide 25 mg

    Arm Description

    Participants will receive vorinostat 300 mg orally once-daily (QD) on Days 1-7 and Days 15-21; lenalidomide 10 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity.

    Participants will receive vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 10 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity.

    Participants will receive vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 15 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity.

    Participants will receive vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 20 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity.

    Participants will receive vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 25 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity.

    Outcomes

    Primary Outcome Measures

    Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
    DLTs consisted of hematologic or non-hemtologic toxicities. Hematologic DLT was any grade (gr) 4 neutropenia lasting ≥7 days, gr 4 thrombocytopenia or gr 5 hematologic toxicity. Non-hematologic DLT was any gr 3, 4 or 5 non-hematologic toxicity with the exception of (1) gr 3 nausea, vomiting, diarrhea or dehydration not compliant with medical care, lasting <48 hours (2) gr 3 acidosis/alkalosis returning to ≤ gr 2 by 48 hours of medical care (3) gr 3 liver function test elevation without symptoms, lasting ≤5 days (4) Gr 3 amylase elevation without symptoms (5) Gr 3 hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia or hyphosphatemia responding to medical care (6) Gr 3 hypercholeresterolemia or hypertriglyceridemia. A drug-related AE causing dose modification of study drug is also considered a DLT. Per protocol DLTs were analyzed in the first 28-day treatment cycle. The number of participants experiencing DLTs is reported here for all participants who got ≥1 dose of study drug.

    Secondary Outcome Measures

    Number of Participants Experiencing Drug-Related Adverse Events (AEs)
    An AE was defined as any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening of a pre-existing condition which is temporally associated with the use of the Sponsor's product is also an AE. An AE was considered related to a drug as determined by the investigator based on exposure (evidence of exposure to drug), time course (time of AE onset versus drug-induced effect), likely cause (AE etiology related or un-related to drug), de-challenge (drug dose reduction/discontinuation) or re-challenge (drug re-exposure). Per protocol participants experiencing drug-related AEs were analyzed at the time of the protocol-specified final statistical analysis with a 3-September (Sep)-2012 data cut-off. The number of participants experiencing drug-related AEs is reported here for all participants who got ≥1 dose of study drug.

    Full Information

    First Posted
    March 17, 2008
    Last Updated
    October 27, 2020
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00642954
    Brief Title
    Vorinostat (MK-0683, SAHA [Suberoylanilide Hydroxamic Acid]) + Lenalidomide + Dexamethasone in Multiple Myeloma (MM) (MK-0683-074)
    Official Title
    A Phase I Study of Vorinostat in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2020
    Overall Recruitment Status
    Completed
    Study Start Date
    February 13, 2008 (Actual)
    Primary Completion Date
    September 3, 2012 (Actual)
    Study Completion Date
    August 20, 2013 (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 Phase I study of vorinostat in combination with lenalidomide and dexamethasone in participants with relapsed or refractory multiple myeloma is to determine the maximum tolerated dose (MTD) as estimated by the incidence of dose-limiting toxicities (DLTs) and recommended Phase 2 dose (RP2D) as estimated by the incidence of drug-related adverse events (AEs).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Relapsed or Refractory Multiple Myeloma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    31 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Level 1: Vorinostat 300 mg + lenalidomide 10 mg
    Arm Type
    Experimental
    Arm Description
    Participants will receive vorinostat 300 mg orally once-daily (QD) on Days 1-7 and Days 15-21; lenalidomide 10 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity.
    Arm Title
    Level 2: Vorinostat 400 mg + lenalidomide 10 mg
    Arm Type
    Experimental
    Arm Description
    Participants will receive vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 10 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity.
    Arm Title
    Level 3: Vorinostat 400 mg + lenalidomide 15 mg
    Arm Type
    Experimental
    Arm Description
    Participants will receive vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 15 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity.
    Arm Title
    Level 4: Vorinostat 400 mg + lenalidomide 20 mg
    Arm Type
    Experimental
    Arm Description
    Participants will receive vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 20 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity.
    Arm Title
    Level 5: Vorinostat 400 mg + lenalidomide 25 mg
    Arm Type
    Experimental
    Arm Description
    Participants will receive vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 25 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity.
    Intervention Type
    Drug
    Intervention Name(s)
    Vorinostat
    Other Intervention Name(s)
    MK-0683, Suberoylanilide hydroxamic acid, Zolinza
    Intervention Description
    Vorinostat 300 mg or 400 mg QD via oral capsule on Days 1-7 and Days 15-21 of each 28-day cycle.
    Intervention Type
    Drug
    Intervention Name(s)
    Lenalidomide
    Other Intervention Name(s)
    Revlimid
    Intervention Description
    Lenalidomide 10 mg, 15 mg, 20 mg or 25 mg QD via oral capsule on Days 1-21 of each 28-day cycle.
    Intervention Type
    Drug
    Intervention Name(s)
    Dexamethasone
    Other Intervention Name(s)
    Decadron
    Intervention Description
    Dexamethasone 40 mg QD via oral tablet on Days 1, 8, 15 and 22 of each 28-day cycle.
    Primary Outcome Measure Information:
    Title
    Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
    Description
    DLTs consisted of hematologic or non-hemtologic toxicities. Hematologic DLT was any grade (gr) 4 neutropenia lasting ≥7 days, gr 4 thrombocytopenia or gr 5 hematologic toxicity. Non-hematologic DLT was any gr 3, 4 or 5 non-hematologic toxicity with the exception of (1) gr 3 nausea, vomiting, diarrhea or dehydration not compliant with medical care, lasting <48 hours (2) gr 3 acidosis/alkalosis returning to ≤ gr 2 by 48 hours of medical care (3) gr 3 liver function test elevation without symptoms, lasting ≤5 days (4) Gr 3 amylase elevation without symptoms (5) Gr 3 hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia or hyphosphatemia responding to medical care (6) Gr 3 hypercholeresterolemia or hypertriglyceridemia. A drug-related AE causing dose modification of study drug is also considered a DLT. Per protocol DLTs were analyzed in the first 28-day treatment cycle. The number of participants experiencing DLTs is reported here for all participants who got ≥1 dose of study drug.
    Time Frame
    Cycle 1 (Up to 28 days)
    Secondary Outcome Measure Information:
    Title
    Number of Participants Experiencing Drug-Related Adverse Events (AEs)
    Description
    An AE was defined as any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening of a pre-existing condition which is temporally associated with the use of the Sponsor's product is also an AE. An AE was considered related to a drug as determined by the investigator based on exposure (evidence of exposure to drug), time course (time of AE onset versus drug-induced effect), likely cause (AE etiology related or un-related to drug), de-challenge (drug dose reduction/discontinuation) or re-challenge (drug re-exposure). Per protocol participants experiencing drug-related AEs were analyzed at the time of the protocol-specified final statistical analysis with a 3-September (Sep)-2012 data cut-off. The number of participants experiencing drug-related AEs is reported here for all participants who got ≥1 dose of study drug.
    Time Frame
    Up to ~55 months (through pre-specified final statistical analysis cut-off date of 3-Sep-2012)
    Other Pre-specified Outcome Measures:
    Title
    Number of Participants Experiencing Best Overall Response Determined by Complete Response (CR), Near Complete Response (NCR), Very Good Partial Response (VGPR), Partial Response (PR), Minimal Response (MR), Stable Disease (SD) or Progressive Disease (PD)
    Description
    Best overall tumor response consisted of CR (negative M-protein immunofixation [IF], <5% bone marrow [BM] plasma cells, no soft tissue plasmacytomas [STP]), NCR (positive M-protein IF, <5% BM plasma cells, no STP), VGPR (≥90% M-protein decrease, <5% BM plasma cells, no STP), PR (≥50% M-protein, BM plasma cells, STP decrease), MR (25-49% M-protein, BM plasma cells, STP decrease), SD (<25% decrease-25% increase in M-protein, BM plasma cells; <25% decrease-increase in definite STP) or PD (≥25% M-protein, BM plasma cells increase; new STP, lesions). Per protocol participants experiencing best overall response by CR, NCR, VGPR, PR, MR, SD or PD were analyzed as a single prespecified analysis at the time of protocol-specified final statistical analysis with a 3-Sep-2012 data cut-off. The number of participants experiencing best overall response by CR, NCR, VGPR, PR, MR, SD or PD is reported here for all participants who got ≥1 dose of study drug and had a post baseline efficacy assessment.
    Time Frame
    Up to ~55 months (through pre-specified final statistical analysis cut-off date of 3-Sep-2012)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Is a male or female at least 18 years old Has relapsed or refractory MM and has had at least one prior therapy Female participants of childbearing potential must have 2 negative serum pregnancy tests prior to receiving the first dose of study drugs Female participants who can become pregnant must agree to use 2 separate forms of effective birth control at the same time, 4 weeks before, while taking, and for 4 weeks after stopping lenalidomide; post menopausal participants should be free from menses for >2 years, or are surgically sterilized Male participant agrees to use an adequate method of contraception for the duration of the study, even if the participant has undergone a successful vasectomy Male participants must agree to use a latex condom during sexual contact with a pregnant female or a female who can become pregnant; this is required for the duration of the study, and for 4 weeks after stopping therapy Has at least 3 weeks washout prior to treatment Is able to swallow capsules and is able to take or tolerate oral medications on a continuous basis Exclusion Criteria: Has prior treatment with a histone deacetylase (HDAC) inhibitor Has prior allogenetic bone marrow transplant Has received intravenous antibiotics, antiviral, or antifungal agents within 2 weeks prior to the start of the study drug Uses illicit drugs, substance abuse or had a recent history (within the last year) of drug or alcohol abuse Is pregnant or breast feeding or expecting to have a baby during the course of the study Has human immunodeficiency virus (HIV) infection Has Hepatitis B/C infection Is currently receiving treatment for another type of cancer other than skin or cervical cancer that has not been in remission for 5 years or longer
    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
    24562384
    Citation
    Siegel DS, Richardson P, Dimopoulos M, Moreau P, Mitsiades C, Weber D, Houp J, Gause C, Vuocolo S, Eid J, Graef T, Anderson KC. Vorinostat in combination with lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma. Blood Cancer J. 2014 Feb 21;4(2):e182. doi: 10.1038/bcj.2014.1. Erratum In: Blood Cancer J. 2014 Apr 11;4:e202.
    Results Reference
    result

    Learn more about this trial

    Vorinostat (MK-0683, SAHA [Suberoylanilide Hydroxamic Acid]) + Lenalidomide + Dexamethasone in Multiple Myeloma (MM) (MK-0683-074)

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