Trial Outcomes & Findings for Phase I Study of MK-0683 in Combination With Bortezomib in Participants With Multiple Myeloma (MK-0683-098) (NCT NCT00858234)

Last Updated: 2021-04-09

Results Overview

The number of participants with ≥1 DLT during Cycle 1 is reported. A DLT is defined as an event considered by the investigator to be related to study treatment, and either: 1) a Grade 3 or 4 non-hematologic event (except for manageable toxicity by supportive care or non-prohibited therapies, or a transient increase in alanine aminotransferase \[ALT\]/aspartate aminotransferase \[AST\]); or 2) a Grade 4 hematologic toxicity except neutropenia or hemoglobin decreased (neutropenia was a DLT if it was Grade 3-4 with fever ≥38.5°C; Grade 3-4 with an infection requiring antibiotic/antifungal therapy; or Grade 4 and lasting ≥5 days).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

9 participants

Primary outcome timeframe

Up to 21 days

Results posted on

2021-04-09

Participant Flow

Adult male and female participants with relapsed and/or refractory multiple myeloma (MM) were enrolled at study sites in Japan.

Participant milestones

Participant milestones
Measure	Vorinostat + Bortezomib Participants undergo ≤3 successive 21-day treatment cycles. During Cycle 1, participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.3 mg/m\^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 2 participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m\^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 3 participants receive vorinostat (300 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m\^2 IV on Days 1, 4, 8, and 11).
Overall Study STARTED	9
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Vorinostat + Bortezomib Participants undergo ≤3 successive 21-day treatment cycles. During Cycle 1, participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.3 mg/m\^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 2 participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m\^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 3 participants receive vorinostat (300 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m\^2 IV on Days 1, 4, 8, and 11).
Overall Study Adverse Event	6
Overall Study Progressive disease	2
Overall Study Status unknown	1

Baseline Characteristics

Phase I Study of MK-0683 in Combination With Bortezomib in Participants With Multiple Myeloma (MK-0683-098)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vorinostat + Bortezomib n=9 Participants Participants undergo ≤3 successive 21-day treatment cycles. During Cycle 1, participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.3 mg/m\^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 2 participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m\^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 3 participants receive vorinostat (300 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m\^2 IV on Days 1, 4, 8, and 11).
Age, Continuous	63.3 Years STANDARD_DEVIATION 11.9 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	9 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 21 days

Population: All treated participants who were not refractory to bortezomib and met all inclusion criteria are included.

Outcome measures

Outcome measures
Measure	Vorinostat + Bortezomib n=6 Participants Participants undergo ≤3 successive 21-day treatment cycles. During Cycle 1, participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.3 mg/m\^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 2 participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m\^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 3 participants receive vorinostat (300 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m\^2 IV on Days 1, 4, 8, and 11).
Number of Participants With Dose-Limiting Toxicity (DLT) During Cycle 1	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 346 days (up to 30 days after the final dose of study treatment)

Population: All treated participants are included.

The number of participants with ≥1 AE is reported. An AE is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study product(s), whether or not considered related to the use of the product(s).

Outcome measures

Outcome measures
Measure	Vorinostat + Bortezomib n=9 Participants Participants undergo ≤3 successive 21-day treatment cycles. During Cycle 1, participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.3 mg/m\^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 2 participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m\^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 3 participants receive vorinostat (300 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m\^2 IV on Days 1, 4, 8, and 11).
Number of Participants With an Adverse Event (AE)	9 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Predose and 0.8, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Days 1 and 11

Population: Participants with data available are included.

The AUC0-24hr of vorinostat in plasma on Days 1 and 11 is reported in participants who also received bortezomib.

Outcome measures

Outcome measures
Measure	Vorinostat + Bortezomib n=9 Participants Participants undergo ≤3 successive 21-day treatment cycles. During Cycle 1, participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.3 mg/m\^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 2 participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m\^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 3 participants receive vorinostat (300 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m\^2 IV on Days 1, 4, 8, and 11).
Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Vorinostat Administered With Bortezomib on Days 1 and 11 Day 1	5.41 µM*hr Interval 4.33 to 6.77
Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Vorinostat Administered With Bortezomib on Days 1 and 11 Day 11	5.84 µM*hr Interval 4.48 to 7.61

Adverse Events

Vorinostat + Bortezomib

Serious events: 3 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Vorinostat + Bortezomib n=9 participants at risk Participants undergo ≤3 successive 21-day treatment cycles. During Cycle 1, participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.3 mg/m\^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 2 participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m\^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 3 participants receive vorinostat (300 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m\^2 IV on Days 1, 4, 8, and 11).
Blood and lymphatic system disorders Disseminated intravascular coagulation	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
General disorders Fatigue	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Infections and infestations Pneumonia	22.2% 2/9 • Number of events 2 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Infections and infestations Pyelonephritis	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Infections and infestations Sepsis	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Metabolism and nutrition disorders Decreased appetite	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.

Other adverse events

Other adverse events
Measure	Vorinostat + Bortezomib n=9 participants at risk Participants undergo ≤3 successive 21-day treatment cycles. During Cycle 1, participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.3 mg/m\^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 2 participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m\^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 3 participants receive vorinostat (300 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m\^2 IV on Days 1, 4, 8, and 11).
Metabolism and nutrition disorders Hypercreatininaemia	11.1% 1/9 • Number of events 3 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Blood and lymphatic system disorders Anaemia	33.3% 3/9 • Number of events 8 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Blood and lymphatic system disorders Leukopenia	100.0% 9/9 • Number of events 98 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Blood and lymphatic system disorders Lymphopenia	66.7% 6/9 • Number of events 32 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Blood and lymphatic system disorders Neutropenia	100.0% 9/9 • Number of events 99 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Blood and lymphatic system disorders Thrombocytopenia	100.0% 9/9 • Number of events 189 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Eye disorders Conjunctivitis	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Gastrointestinal disorders Abdominal discomfort	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Gastrointestinal disorders Constipation	66.7% 6/9 • Number of events 16 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Gastrointestinal disorders Diarrhoea	100.0% 9/9 • Number of events 44 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Gastrointestinal disorders Dry mouth	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Gastrointestinal disorders Dyspepsia	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Gastrointestinal disorders Gingival bleeding	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Gastrointestinal disorders Gingivitis	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Gastrointestinal disorders Mouth haemorrhage	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Gastrointestinal disorders Nausea	88.9% 8/9 • Number of events 31 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Gastrointestinal disorders Stomatitis	22.2% 2/9 • Number of events 3 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Gastrointestinal disorders Vomiting	77.8% 7/9 • Number of events 19 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
General disorders Fatigue	55.6% 5/9 • Number of events 18 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
General disorders Injection site reaction	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
General disorders Malaise	22.2% 2/9 • Number of events 2 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
General disorders Pyrexia	33.3% 3/9 • Number of events 9 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Hepatobiliary disorders Drug-induced liver injury	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Hepatobiliary disorders Hepatic function abnormal	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Infections and infestations Enteritis infectious	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Infections and infestations Herpes zoster	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Infections and infestations Hordeolum	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Infections and infestations Nasopharyngitis	22.2% 2/9 • Number of events 3 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Infections and infestations Pneumonia	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Infections and infestations Sinusitis	11.1% 1/9 • Number of events 2 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Infections and infestations Upper respiratory tract infection	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Investigations Alanine aminotransferase increased	33.3% 3/9 • Number of events 8 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Investigations Aspartate aminotransferase increased	44.4% 4/9 • Number of events 6 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Investigations Blood albumin decreased	22.2% 2/9 • Number of events 2 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Investigations Blood alkaline phosphatase increased	11.1% 1/9 • Number of events 2 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Investigations Blood creatinine increased	22.2% 2/9 • Number of events 9 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Investigations Blood glucose increased	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Investigations Blood phosphorus decreased	22.2% 2/9 • Number of events 2 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Investigations Blood potassium increased	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Investigations Electrocardiogram QT prolonged	33.3% 3/9 • Number of events 4 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Investigations Electrocardiogram ST-T segment depression	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Investigations Gamma-glutamyltransferase increased	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Investigations Lymphocyte count decreased	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Investigations Neutrophil count decreased	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Investigations Weight decreased	33.3% 3/9 • Number of events 7 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Metabolism and nutrition disorders Decreased appetite	88.9% 8/9 • Number of events 24 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Metabolism and nutrition disorders Dehydration	22.2% 2/9 • Number of events 4 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Metabolism and nutrition disorders Hyperglycaemia	22.2% 2/9 • Number of events 20 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Metabolism and nutrition disorders Hyperkalaemia	11.1% 1/9 • Number of events 2 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Metabolism and nutrition disorders Hypermagnesaemia	11.1% 1/9 • Number of events 2 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Metabolism and nutrition disorders Hyperuricaemia	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Metabolism and nutrition disorders Hypoalbuminaemia	22.2% 2/9 • Number of events 2 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Metabolism and nutrition disorders Hypokalaemia	55.6% 5/9 • Number of events 24 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Metabolism and nutrition disorders Hypomagnesaemia	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Metabolism and nutrition disorders Hyponatraemia	11.1% 1/9 • Number of events 5 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Metabolism and nutrition disorders Hypophosphataemia	22.2% 2/9 • Number of events 2 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Metabolism and nutrition disorders Tumour lysis syndrome	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Nervous system disorders Dizziness	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Nervous system disorders Dysgeusia	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Nervous system disorders Headache	11.1% 1/9 • Number of events 2 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Nervous system disorders Hypoaesthesia	22.2% 2/9 • Number of events 3 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Nervous system disorders Neuropathy peripheral	11.1% 1/9 • Number of events 5 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Nervous system disorders Peripheral sensory neuropathy	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Psychiatric disorders Insomnia	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Respiratory, thoracic and mediastinal disorders Dysphonia	11.1% 1/9 • Number of events 2 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Skin and subcutaneous tissue disorders Dry skin	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Skin and subcutaneous tissue disorders Haemorrhage subcutaneous	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Skin and subcutaneous tissue disorders Onychoclasis	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Skin and subcutaneous tissue disorders Petechiae	11.1% 1/9 • Number of events 2 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Skin and subcutaneous tissue disorders Purpura	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Skin and subcutaneous tissue disorders Rash	22.2% 2/9 • Number of events 2 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Vascular disorders Flushing	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Vascular disorders Hypertension	22.2% 2/9 • Number of events 3 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.
Vascular disorders Orthostatic hypotension	11.1% 1/9 • Number of events 1 • Up to 346 days (up to 30 days after the final dose of study treatment) All treated participants are included.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation.
Publication restrictions are in place

Restriction type: OTHER