Trial Outcomes & Findings for Tivantinib in Treating Patients With Relapsed, or Relapsed and Refractory Multiple Myeloma (NCT NCT01447914)

Last Updated: 2019-08-28

Results Overview

ORR using International Myeloma Working Group Response Criteria, achieve at least a partial response (PR) or better: Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR): CR: Negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow; sCR: CR+Normal free light chain ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; PR: ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90%; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \<100mg per 24 hour; Stable Disease (SD): Not CR, VGPR, PR or progressive disease; Progressive Disease (PD):\>25% from lowest value Serum and/or Urine M-component, new lesions or soft tissue plasmacytomas, or hypercalcemia.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

16 participants

Primary outcome timeframe

Up to 30 days

Results posted on

2019-08-28

Participant Flow

Total Recruitment Period: November 30, 2011 to August 1, 2013. All recruitment done at University of Texas (UT) MD Anderson Cancer Center.

Participant milestones

Participant milestones
Measure	Tivantinib Treatment Oral Tivantinib 360 mg twice daily continuously for each day of every 28 day treatment cycle (taken as three tablets of 120 mg each)
Overall Study STARTED	16
Overall Study COMPLETED	16
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Tivantinib in Treating Patients With Relapsed, or Relapsed and Refractory Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tivantinib Treatment n=16 Participants Oral Tivantinib 360 mg twice daily continuously for each day of every 28 day treatment cycle (taken as three tablets of 120 mg each)
Age, Continuous	66.3 years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 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	2 Participants n=5 Participants
Race (NIH/OMB) White	13 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
Region of Enrollment United States	16 participants n=5 Participants
Prior Stem Cell Transplantation (SCT) Prior SCT	10 participants n=5 Participants
Prior Stem Cell Transplantation (SCT) No Prior SCT	6 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 30 days

Population: Proportion of participants reported on an intent-to-treat basis.

Outcome measures

Outcome measures
Measure	Tivantinib Treatment n=16 Participants Oral Tivantinib 360 mg twice daily continuously for each day of every 28 day treatment cycle (taken as three tablets of 120 mg each)
Overall Response Rate (ORR) Stable Disease	4 participants
Overall Response Rate (ORR) Progressive Disease	7 participants
Overall Response Rate (ORR) Not Evaluable	5 participants

PRIMARY outcome

Timeframe: Up to 30 days

Toxicities with a grade 3 nonhematologic or grade 4 hematologic toxicities according to CTCAE, version 4. Grade 3 and estimated with a 95% credible interval. Summary statistics will be provided for continuous variables.

Outcome measures

Outcome measures
Measure	Tivantinib Treatment n=16 Participants Oral Tivantinib 360 mg twice daily continuously for each day of every 28 day treatment cycle (taken as three tablets of 120 mg each)
Toxicities of Single Agent Tivantinib: Grade 3 Nonhematologic or Grade 4 Hematologic Toxicities According to the Common Terminology Criteria for Adverse Events (CTCAE), Version 4 Non-Hematological Grade 3- Hypertension	1 Participants
Toxicities of Single Agent Tivantinib: Grade 3 Nonhematologic or Grade 4 Hematologic Toxicities According to the Common Terminology Criteria for Adverse Events (CTCAE), Version 4 Non Hematological Grade 3- Syncope	2 Participants
Toxicities of Single Agent Tivantinib: Grade 3 Nonhematologic or Grade 4 Hematologic Toxicities According to the Common Terminology Criteria for Adverse Events (CTCAE), Version 4 Non Hematological Grade 3- Pulmonari emboli	1 Participants
Toxicities of Single Agent Tivantinib: Grade 3 Nonhematologic or Grade 4 Hematologic Toxicities According to the Common Terminology Criteria for Adverse Events (CTCAE), Version 4 Hematological Grade 3- Neutropenia	4 Participants
Toxicities of Single Agent Tivantinib: Grade 3 Nonhematologic or Grade 4 Hematologic Toxicities According to the Common Terminology Criteria for Adverse Events (CTCAE), Version 4 Non Hematological Grade 3- Fatigue	1 Participants
Toxicities of Single Agent Tivantinib: Grade 3 Nonhematologic or Grade 4 Hematologic Toxicities According to the Common Terminology Criteria for Adverse Events (CTCAE), Version 4 Non Hematological Grade 3- Cough	1 Participants
Toxicities of Single Agent Tivantinib: Grade 3 Nonhematologic or Grade 4 Hematologic Toxicities According to the Common Terminology Criteria for Adverse Events (CTCAE), Version 4 Non Hematological Grade 3- Bacteremia	1 Participants
Toxicities of Single Agent Tivantinib: Grade 3 Nonhematologic or Grade 4 Hematologic Toxicities According to the Common Terminology Criteria for Adverse Events (CTCAE), Version 4 Non Hematological Grade 3- Anorectal Infection	1 Participants
Toxicities of Single Agent Tivantinib: Grade 3 Nonhematologic or Grade 4 Hematologic Toxicities According to the Common Terminology Criteria for Adverse Events (CTCAE), Version 4 Non Hematological Grade 3- Rectal Pain	1 Participants
Toxicities of Single Agent Tivantinib: Grade 3 Nonhematologic or Grade 4 Hematologic Toxicities According to the Common Terminology Criteria for Adverse Events (CTCAE), Version 4 Non Hematological Grade 3- Rib Pain	1 Participants

SECONDARY outcome

Timeframe: From registration on trial to next treatment or death due to any cause, whichever comes first

Kaplan and Meier product limit methods will be used to estimate the TTNT with 95% confidence intervals.

Outcome measures

Outcome measures
Measure	Tivantinib Treatment n=16 Participants Oral Tivantinib 360 mg twice daily continuously for each day of every 28 day treatment cycle (taken as three tablets of 120 mg each)
Time to Next Treatment (TTNT)	4 number of months Interval 1.0 to 15.0

OTHER_PRE_SPECIFIED outcome

Timeframe: From first observation of partial response to the time of disease progression, assessed up to 30 days

Population: No participants responded to the therapy and no analyses were done

Kaplan and Meier product limit methods will be used to estimate the DOR with 95% confidence intervals.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: From start of the treatment to disease progression or death (regardless of cause of death), whichever comes first, assessed up to 30 days

Population: No participants responded to the therapy and no analyses was done.

Kaplan and Meier product limit methods will be used to estimate the median PFS with 95% confidence intervals. Furthermore, the univariate and multivariate Cox proportional hazards regression model will be used to identify prognostic factors for PFS.

Outcome measures

Outcome data not reported

POST_HOC outcome

Timeframe: From start of participant treatment to completion or disease progression; assessed up to 16 months

Population: No participants responded to the therapy and no analyses were done

Number of treatment cycles completed by study participants.

Outcome measures

Outcome measures
Measure	Tivantinib Treatment n=16 Participants Oral Tivantinib 360 mg twice daily continuously for each day of every 28 day treatment cycle (taken as three tablets of 120 mg each)
Cycles of Tivantinib Treatment Administered	4 number of treatment cycles Interval 1.0 to 15.0

Adverse Events

Tivantinib Treatment

Serious events: 8 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tivantinib Treatment n=16 participants at risk Oral Tivantinib 360 mg twice daily continuously for each day of every 28 day treatment cycle (taken as three tablets of 120 mg each)
Infections and infestations Bacteremia Infection	6.2% 1/16 • Number of events 1 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Respiratory, thoracic and mediastinal disorders Cough	6.2% 1/16 • Number of events 1 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
General disorders Fatigue	6.2% 1/16 • Number of events 1 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Cardiac disorders Hypertension	6.2% 1/16 • Number of events 1 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Blood and lymphatic system disorders Neutropenia (Neutrophil count decreased)	31.2% 5/16 • Number of events 9 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
General disorders Pain	12.5% 2/16 • Number of events 2 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Respiratory, thoracic and mediastinal disorders Multiple pulmonary emboli	6.2% 1/16 • Number of events 1 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Cardiac disorders Syncope	12.5% 2/16 • Number of events 2 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Infections and infestations Anorectal Infection	6.2% 1/16 • Number of events 1 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.

Other adverse events

Other adverse events
Measure	Tivantinib Treatment n=16 participants at risk Oral Tivantinib 360 mg twice daily continuously for each day of every 28 day treatment cycle (taken as three tablets of 120 mg each)
Immune system disorders Allergic rhinitis	12.5% 2/16 • Number of events 2 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Skin and subcutaneous tissue disorders Alopecia	12.5% 2/16 • Number of events 2 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Blood and lymphatic system disorders Anemia	18.8% 3/16 • Number of events 3 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Nervous system disorders Anxiety	12.5% 2/16 • Number of events 2 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Eye disorders Blurred vision	12.5% 2/16 • Number of events 5 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
General disorders Chills	6.2% 1/16 • Number of events 1 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Gastrointestinal disorders Constipation	18.8% 3/16 • Number of events 5 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Respiratory, thoracic and mediastinal disorders Cough	31.2% 5/16 • Number of events 6 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Metabolism and nutrition disorders Creatinine increased	6.2% 1/16 • Number of events 1 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Nervous system disorders Depression	6.2% 1/16 • Number of events 1 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Gastrointestinal disorders Diarrhea	37.5% 6/16 • Number of events 7 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Nervous system disorders Dizziness	37.5% 6/16 • Number of events 8 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Eye disorders Dry eye	18.8% 3/16 • Number of events 4 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Respiratory, thoracic and mediastinal disorders Dyspnea	37.5% 6/16 • Number of events 9 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Musculoskeletal and connective tissue disorders Edema limbs	12.5% 2/16 • Number of events 3 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
General disorders Fatigue	62.5% 10/16 • Number of events 14 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Infections and infestations Fever	12.5% 2/16 • Number of events 2 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Infections and infestations Flu like symptoms	6.2% 1/16 • Number of events 1 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Musculoskeletal and connective tissue disorders Gait distrubance	6.2% 1/16 • Number of events 1 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Gastrointestinal disorders Diverticulitis flare	6.2% 1/16 • Number of events 1 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Musculoskeletal and connective tissue disorders Muscle Discomfort	18.8% 3/16 • Number of events 3 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Nervous system disorders Headache	12.5% 2/16 • Number of events 2 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Skin and subcutaneous tissue disorders Hyperhidrosis	6.2% 1/16 • Number of events 1 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Cardiac disorders Hypertension	18.8% 3/16 • Number of events 3 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Metabolism and nutrition disorders Hypokalemia	6.2% 1/16 • Number of events 1 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Endocrine disorders Hypothyroidism	6.2% 1/16 • Number of events 1 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
General disorders Insomnia	12.5% 2/16 • Number of events 2 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Nervous system disorders Memory impairment	31.2% 5/16 • Number of events 5 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Endocrine disorders Diabetes	6.2% 1/16 • Number of events 1 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Cardiac disorders Hyperlipidemia	6.2% 1/16 • Number of events 1 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Musculoskeletal and connective tissue disorders Myalgia	37.5% 6/16 • Number of events 9 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Gastrointestinal disorders Nausea	12.5% 2/16 • Number of events 2 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Blood and lymphatic system disorders Neutrophil count decreased	31.2% 5/16 • Number of events 6 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
General disorders Pain	43.8% 7/16 • Number of events 12 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Nervous system disorders Paresthesia	6.2% 1/16 • Number of events 1 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Nervous system disorders Peripheral motor neuropathy	62.5% 10/16 • Number of events 11 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Blood and lymphatic system disorders Platelet count decreased	12.5% 2/16 • Number of events 2 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Skin and subcutaneous tissue disorders Rash acneiform	6.2% 1/16 • Number of events 3 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Renal and urinary disorders Nocturia	37.5% 6/16 • Number of events 6 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Respiratory, thoracic and mediastinal disorders Rhinorrhea	25.0% 4/16 • Number of events 4 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Cardiac disorders Sinus bradycardia	18.8% 3/16 • Number of events 3 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Respiratory, thoracic and mediastinal disorders Sinusitis	6.2% 1/16 • Number of events 1 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	12.5% 2/16 • Number of events 2 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Ear and labyrinth disorders Tinnitus	6.2% 1/16 • Number of events 1 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Respiratory, thoracic and mediastinal disorders Upper Respiratory Infection	25.0% 4/16 • Number of events 4 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Renal and urinary disorders Urinary tract pain	6.2% 1/16 • Number of events 1 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Eye disorders Watering eyes	12.5% 2/16 • Number of events 2 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Respiratory, thoracic and mediastinal disorders Wheezing	6.2% 1/16 • Number of events 1 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Respiratory, thoracic and mediastinal disorders Congestion	6.2% 1/16 • Number of events 1 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Respiratory, thoracic and mediastinal disorders Sore Throat	6.2% 1/16 • Number of events 1 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Respiratory, thoracic and mediastinal disorders Postnasal Drip	6.2% 1/16 • Number of events 1 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.
Skin and subcutaneous tissue disorders Rash maculo-papular	6.2% 1/16 • Number of events 2 • Adverse events collected till 30 days of the last dose of the investigational agent and include all who receive any amount of study drug. Overall collection period January 2012 to February 2014.

Additional Information

Robert Orlowski, MD, PhD / Professor, Department of Lymphoma/Myeloma

University of Texas (UT) MD Anderson Cancer Center

Phone: 713-792-2860

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60