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

October 27, 2020 updated by: Merck Sharp & Dohme LLC

A Phase I Study of Vorinostat in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Level 1: Vorinostat 300 mg + lenalidomide 10 mg
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.
Drug: Vorinostat
Vorinostat 300 mg or 400 mg QD via oral capsule on Days 1-7 and Days 15-21 of each 28-day cycle.
Other Names:
  • Zolinza
  • MK-0683
  • Suberoylanilide hydroxamic acid
Drug: Lenalidomide
Lenalidomide 10 mg, 15 mg, 20 mg or 25 mg QD via oral capsule on Days 1-21 of each 28-day cycle.
Other Names:
  • Revlimid
Drug: Dexamethasone
Dexamethasone 40 mg QD via oral tablet on Days 1, 8, 15 and 22 of each 28-day cycle.
Other Names:
  • Decadron
Experimental: Level 2: Vorinostat 400 mg + lenalidomide 10 mg
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.
Drug: Vorinostat
Vorinostat 300 mg or 400 mg QD via oral capsule on Days 1-7 and Days 15-21 of each 28-day cycle.
Other Names:
  • Zolinza
  • MK-0683
  • Suberoylanilide hydroxamic acid
Drug: Lenalidomide
Lenalidomide 10 mg, 15 mg, 20 mg or 25 mg QD via oral capsule on Days 1-21 of each 28-day cycle.
Other Names:
  • Revlimid
Drug: Dexamethasone
Dexamethasone 40 mg QD via oral tablet on Days 1, 8, 15 and 22 of each 28-day cycle.
Other Names:
  • Decadron
Experimental: Level 3: Vorinostat 400 mg + lenalidomide 15 mg
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.
Drug: Vorinostat
Vorinostat 300 mg or 400 mg QD via oral capsule on Days 1-7 and Days 15-21 of each 28-day cycle.
Other Names:
  • Zolinza
  • MK-0683
  • Suberoylanilide hydroxamic acid
Drug: Lenalidomide
Lenalidomide 10 mg, 15 mg, 20 mg or 25 mg QD via oral capsule on Days 1-21 of each 28-day cycle.
Other Names:
  • Revlimid
Drug: Dexamethasone
Dexamethasone 40 mg QD via oral tablet on Days 1, 8, 15 and 22 of each 28-day cycle.
Other Names:
  • Decadron
Experimental: Level 4: Vorinostat 400 mg + lenalidomide 20 mg
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.
Drug: Vorinostat
Vorinostat 300 mg or 400 mg QD via oral capsule on Days 1-7 and Days 15-21 of each 28-day cycle.
Other Names:
  • Zolinza
  • MK-0683
  • Suberoylanilide hydroxamic acid
Drug: Lenalidomide
Lenalidomide 10 mg, 15 mg, 20 mg or 25 mg QD via oral capsule on Days 1-21 of each 28-day cycle.
Other Names:
  • Revlimid
Drug: Dexamethasone
Dexamethasone 40 mg QD via oral tablet on Days 1, 8, 15 and 22 of each 28-day cycle.
Other Names:
  • Decadron
Experimental: Level 5: Vorinostat 400 mg + lenalidomide 25 mg
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.
Drug: Vorinostat
Vorinostat 300 mg or 400 mg QD via oral capsule on Days 1-7 and Days 15-21 of each 28-day cycle.
Other Names:
  • Zolinza
  • MK-0683
  • Suberoylanilide hydroxamic acid
Drug: Lenalidomide
Lenalidomide 10 mg, 15 mg, 20 mg or 25 mg QD via oral capsule on Days 1-21 of each 28-day cycle.
Other Names:
  • Revlimid
Drug: Dexamethasone
Dexamethasone 40 mg QD via oral tablet on Days 1, 8, 15 and 22 of each 28-day cycle.
Other Names:
  • Decadron

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
Time Frame: Cycle 1 (Up to 28 days)
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.
Cycle 1 (Up to 28 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Experiencing Drug-Related Adverse Events (AEs)
Time Frame: Up to ~55 months (through pre-specified final statistical analysis cut-off date of 3-Sep-2012)
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.
Up to ~55 months (through pre-specified final statistical analysis cut-off date of 3-Sep-2012)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
Time Frame: Up to ~55 months (through pre-specified final statistical analysis cut-off date of 3-Sep-2012)
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.
Up to ~55 months (through pre-specified final statistical analysis cut-off date of 3-Sep-2012)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 13, 2008

Primary Completion (Actual)

September 3, 2012

Study Completion (Actual)

August 20, 2013

Study Registration Dates

First Submitted

March 17, 2008

First Submitted That Met QC Criteria

March 21, 2008

First Posted (Estimate)

March 25, 2008

Study Record Updates

Last Update Posted (Actual)

November 18, 2020

Last Update Submitted That Met QC Criteria

October 27, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0683-074
  • 2007_511 (Other Identifier: Merck)
  • 2007-001033-34 (EudraCT Number)
  • MK-0683-074 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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