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

NCT00642954 | Completed Phase 1 Results

• 4 other identifiers: 0683-0742007_5112007-001033-34MK-0683-074
• Study Type: interventional
• Target: 31
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Relapsed or Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• 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.

  Cycle 1 (Up to 28 days)

Secondary Outcomes (1)

• Number of Participants Experiencing Drug-Related Adverse Events (AEs)

  Up to ~55 months (through pre-specified final statistical analysis cut-off date of 3-Sep-2012)

Other Outcomes (1)

• 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)

  Up to ~55 months (through pre-specified final statistical analysis cut-off date of 3-Sep-2012)

Study Arms (5)

Level 1: Vorinostat 300 mg + lenalidomide 10 mg

EXPERIMENTAL

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; Drug: Lenalidomide; Drug: Dexamethasone

Level 2: Vorinostat 400 mg + lenalidomide 10 mg

EXPERIMENTAL

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; Drug: Lenalidomide; Drug: Dexamethasone

Level 3: Vorinostat 400 mg + lenalidomide 15 mg

EXPERIMENTAL

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; Drug: Lenalidomide; Drug: Dexamethasone

Level 4: Vorinostat 400 mg + lenalidomide 20 mg

EXPERIMENTAL

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; Drug: Lenalidomide; Drug: Dexamethasone

Level 5: Vorinostat 400 mg + lenalidomide 25 mg

EXPERIMENTAL

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; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Vorinostat DRUG

Vorinostat 300 mg or 400 mg QD via oral capsule on Days 1-7 and Days 15-21 of each 28-day cycle.

Also known as: MK-0683, Suberoylanilide hydroxamic acid, Zolinza

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

Lenalidomide DRUG

Lenalidomide 10 mg, 15 mg, 20 mg or 25 mg QD via oral capsule on Days 1-21 of each 28-day cycle.

Also known as: Revlimid

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

Dexamethasone DRUG

Dexamethasone 40 mg QD via oral tablet on Days 1, 8, 15 and 22 of each 28-day cycle.

Also known as: Decadron

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 24562384 RESULT

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Interventions

Vorinostat; Lenalidomide; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2008
• First Posted: March 25, 2008
• Study Start: February 13, 2008
• Primary Completion: September 3, 2012
• Study Completion: August 20, 2013
• Last Updated: November 18, 2020
• Results First Posted: November 18, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will share