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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Relapsed or Refractory Multiple Myeloma

Treatments: Drug: Lenalidomide; Drug: Dexamethasone; Drug: Vorinostat

Study type: Interventional

Funder types: Industry

Identifiers

NCT00642954

2007_511 (Other Identifier)

2007-001033-34 (EudraCT Number)

MK-0683-074 (Other Identifier)

0683-074

Details and patient eligibility

About

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).

Enrollment: 31 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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31 participants in 5 patient groups

Level 1: Vorinostat 300 mg + lenalidomide 10 mg

Experimental group

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.

Treatment:

Drug: Vorinostat

Drug: Dexamethasone

Drug: Lenalidomide

Level 2: Vorinostat 400 mg + lenalidomide 10 mg

Experimental group

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.

Treatment:

Drug: Vorinostat

Drug: Dexamethasone

Drug: Lenalidomide

Level 3: Vorinostat 400 mg + lenalidomide 15 mg

Experimental group

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.

Treatment:

Drug: Vorinostat

Drug: Dexamethasone

Drug: Lenalidomide

Level 4: Vorinostat 400 mg + lenalidomide 20 mg

Experimental group

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.

Treatment:

Drug: Vorinostat

Drug: Dexamethasone

Drug: Lenalidomide

Level 5: Vorinostat 400 mg + lenalidomide 25 mg

Experimental group

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.

Treatment:

Drug: Vorinostat

Drug: Dexamethasone

Drug: Lenalidomide