Trial Outcomes & Findings for Phase 2 Clinical Trial of NPI-0052 in Patients With Relapsed or Relapsed/Refractory Multiple Myeloma (NCT NCT00461045)
NCT ID: NCT00461045
Last Updated: 2017-12-19
Results Overview
Disease response and progression were determined by the investigator using the International Myeloma Working Group Uniform Response Criteria (IMWG-URC). Overall response rate includes patients with a best response of PR of better. Stringent complete response (CR) includes immunophenotypic CR and molecular CR in addition to stringent CR.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
15 participants
Primary outcome timeframe
Through study completion, an average of 6.09 weeks.
Results posted on
2017-12-19
Participant Flow
Participant milestones
| Measure |
MRZ 0.5 mg/m^2
Twice-weekly dosing with 2-hour IV infusions on days 1,4,8, and 11 of 3-week cycles
|
|---|---|
|
Overall Study
STARTED
|
15
|
|
Overall Study
COMPLETED
|
15
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Phase 2 Clinical Trial of NPI-0052 in Patients With Relapsed or Relapsed/Refractory Multiple Myeloma
Baseline characteristics by cohort
| Measure |
MRZ 0.5 mg/m^2
n=15 Participants
Twice-weekly dosing with 2-hour IV infusions on days 1,4,8, and 11 of 3-week cycles
|
|---|---|
|
Age, Continuous
|
61.9 years
STANDARD_DEVIATION 8.02 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
15 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
|
2 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
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
10 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
|
15 participants
n=5 Participants
|
|
Baseline Height
|
170.97 cm
STANDARD_DEVIATION 12.152 • n=5 Participants
|
|
Baseline Weight
|
77.27 kg
STANDARD_DEVIATION 17.825 • n=5 Participants
|
|
Body Surface Area (BSA)
|
1.893 m^2
STANDARD_DEVIATION 0.2629 • n=5 Participants
|
|
Fertility Status
Potential able to bear children
|
0 Participants
n=5 Participants
|
|
Fertility Status
Surgically sterile
|
1 Participants
n=5 Participants
|
|
Fertility Status
Post menopausal
|
4 Participants
n=5 Participants
|
|
Fertility Status
Male
|
10 Participants
n=5 Participants
|
|
Karnofsky Performance Status (KPS) Score
|
87.3 KPS Score
n=5 Participants
|
|
Time Since Initial Diagnosis
|
5.2 years
STANDARD_DEVIATION 3.79 • n=5 Participants
|
|
Number of Relapses
1 Relapse
|
0 participants
n=5 Participants
|
|
Number of Relapses
2 Relapses
|
2 participants
n=5 Participants
|
|
Number of Relapses
3 Relapses
|
2 participants
n=5 Participants
|
|
Number of Relapses
>3 Relapses
|
11 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Through study completion, an average of 6.09 weeks.Disease response and progression were determined by the investigator using the International Myeloma Working Group Uniform Response Criteria (IMWG-URC). Overall response rate includes patients with a best response of PR of better. Stringent complete response (CR) includes immunophenotypic CR and molecular CR in addition to stringent CR.
Outcome measures
| Measure |
MRZ 0.5 mg/m^2
n=15 Participants
Twice-weekly dosing with 2-hour IV infusions on days 1,4,8, and 11 of 3-week cycles
|
|---|---|
|
Number of Patients Exhibiting a Given Overall Response as Determined by Investigator
Stringent Complete Response (sCR) or better
|
0 participants
|
|
Number of Patients Exhibiting a Given Overall Response as Determined by Investigator
Complete Response (CR)
|
0 participants
|
|
Number of Patients Exhibiting a Given Overall Response as Determined by Investigator
Very Good Partial Response (VGPR)
|
0 participants
|
|
Number of Patients Exhibiting a Given Overall Response as Determined by Investigator
Partial Response (PR)
|
0 participants
|
|
Number of Patients Exhibiting a Given Overall Response as Determined by Investigator
Minimal Response (MR)
|
0 participants
|
|
Number of Patients Exhibiting a Given Overall Response as Determined by Investigator
Stable Disease (SD)
|
4 participants
|
|
Number of Patients Exhibiting a Given Overall Response as Determined by Investigator
Progressive Disease (PD)
|
9 participants
|
|
Number of Patients Exhibiting a Given Overall Response as Determined by Investigator
Not Evaluated
|
2 participants
|
SECONDARY outcome
Timeframe: Through study completion, an average of 6.09 weeks.Duration of treatment is defined as the last dose date minus the first dose date of the dose cohort plus 1 expressed in weeks.
Outcome measures
| Measure |
MRZ 0.5 mg/m^2
n=15 Participants
Twice-weekly dosing with 2-hour IV infusions on days 1,4,8, and 11 of 3-week cycles
|
|---|---|
|
Duration of MRZ Treatment
|
6.09 weeks
Standard Deviation 4.661
|
SECONDARY outcome
Timeframe: Through study completion, an average of 6.09 weeks.Outcome measures
| Measure |
MRZ 0.5 mg/m^2
n=15 Participants
Twice-weekly dosing with 2-hour IV infusions on days 1,4,8, and 11 of 3-week cycles
|
|---|---|
|
Number of Cycles of Marizomib (MRZ)
|
2.6 cycles
Standard Deviation 1.45
|
SECONDARY outcome
Timeframe: Through study completion, an average of 6.09 weeks.A patient was counted in a cycle if the patient received at least one dose of study drug during the cycle.
Outcome measures
| Measure |
MRZ 0.5 mg/m^2
n=15 Participants
Twice-weekly dosing with 2-hour IV infusions on days 1,4,8, and 11 of 3-week cycles
|
|---|---|
|
Number of Patients Receiving Marizomib (MRZ) in Each Cycle
Cycle 1
|
15 Participants
|
|
Number of Patients Receiving Marizomib (MRZ) in Each Cycle
Cycle 2
|
12 Participants
|
|
Number of Patients Receiving Marizomib (MRZ) in Each Cycle
Cycle 3
|
6 Participants
|
|
Number of Patients Receiving Marizomib (MRZ) in Each Cycle
Cycle 4
|
3 Participants
|
|
Number of Patients Receiving Marizomib (MRZ) in Each Cycle
Cycle 5
|
2 Participants
|
|
Number of Patients Receiving Marizomib (MRZ) in Each Cycle
Cycle 6
|
1 Participants
|
SECONDARY outcome
Timeframe: Through study completion, an average of 6.09 weeks.Adverse events were graded using NCI-CTCAE (version 4.3). TEAEs are defined as any adverse event with an onset date between the date of first dose and 30 days after the date of last dose of any study drug. Treatment-related adverse events are adverse events considered related to at least one study drug by the investigator (NPI-002, dexamethasone), including those with unknown relationship.
Outcome measures
| Measure |
MRZ 0.5 mg/m^2
n=15 Participants
Twice-weekly dosing with 2-hour IV infusions on days 1,4,8, and 11 of 3-week cycles
|
|---|---|
|
Number of Patients With Treatment Emergent Adverse Events (TEAEs)
At least one TEAE
|
15 Participants
|
|
Number of Patients With Treatment Emergent Adverse Events (TEAEs)
At least one treatment related TEAE
|
14 Participants
|
|
Number of Patients With Treatment Emergent Adverse Events (TEAEs)
At least one NPI-0052 related TEAE
|
13 Participants
|
|
Number of Patients With Treatment Emergent Adverse Events (TEAEs)
At least one grade ≥3 TEAE
|
12 Participants
|
|
Number of Patients With Treatment Emergent Adverse Events (TEAEs)
At least one treatment related grade ≥3 TEAE
|
8 Participants
|
|
Number of Patients With Treatment Emergent Adverse Events (TEAEs)
At least one NPI-0052 related grade ≥3 TEAE
|
5 Participants
|
|
Number of Patients With Treatment Emergent Adverse Events (TEAEs)
At least one serious TEAE
|
7 Participants
|
|
Number of Patients With Treatment Emergent Adverse Events (TEAEs)
At least one treatment related serious TEAE
|
4 Participants
|
|
Number of Patients With Treatment Emergent Adverse Events (TEAEs)
At least one NPI-0052 related serious TEAE
|
1 Participants
|
SECONDARY outcome
Timeframe: Through study completion, an average of 6.09 weeks.Adverse events were graded using NCI-CTCAE (version 4.3). TEAEs are defined as any adverse event with an onset date between the date of first dose and 30 days after the date of last dose of any study drug. Treatment-related adverse events are adverse events considered related to at least one study drug by the investigator (NPI-002, dexamethasone), including those with unknown relationship.
Outcome measures
| Measure |
MRZ 0.5 mg/m^2
n=15 Participants
Twice-weekly dosing with 2-hour IV infusions on days 1,4,8, and 11 of 3-week cycles
|
|---|---|
|
Number of Treatment Emergent Adverse Events (TEAEs)
Number of grade ≥3 TEAEs
|
41 TEAEs
|
|
Number of Treatment Emergent Adverse Events (TEAEs)
Number of treatment related grade ≥3 TEAEs
|
16 TEAEs
|
|
Number of Treatment Emergent Adverse Events (TEAEs)
Number of NPI-0052 realted grade ≥3 TEAEs
|
9 TEAEs
|
|
Number of Treatment Emergent Adverse Events (TEAEs)
Number of serious TEAEs
|
21 TEAEs
|
|
Number of Treatment Emergent Adverse Events (TEAEs)
Number of treatment related serious TEAEs
|
5 TEAEs
|
|
Number of Treatment Emergent Adverse Events (TEAEs)
Number of NPI-0052 related serious TEAEs
|
1 TEAEs
|
|
Number of Treatment Emergent Adverse Events (TEAEs)
Number of treatment related TEAEs
|
73 TEAEs
|
|
Number of Treatment Emergent Adverse Events (TEAEs)
Number of NPI-0052 related TEAEs
|
50 TEAEs
|
|
Number of Treatment Emergent Adverse Events (TEAEs)
Number of TEAEs
|
149 TEAEs
|
SECONDARY outcome
Timeframe: Samples collected on Cycle 1 Day 1 and Cycle 1 Day 11.Population: The sponsor elected not to analyze the pharmacokinetic (PK) samples collected, therefore, no PK results are obtained.
Outcome measures
Outcome data not reported
Adverse Events
MRZ 0.5 mg/m^2
Serious events: 7 serious events
Other events: 15 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
MRZ 0.5 mg/m^2
n=15 participants at risk
Twice-weekly dosing with 2-hour IV infusions on days 1,4,8, and 11 of 3-week cycles
|
|---|---|
|
Infections and infestations
Sepsis
|
6.7%
1/15
|
|
Infections and infestations
Pneumonia
|
6.7%
1/15
|
|
Renal and urinary disorders
Renal failure acute
|
13.3%
2/15
|
|
Cardiac disorders
Cardiac Failure Congestive
|
13.3%
2/15
|
|
Cardiac disorders
Atrial Fibrillation
|
6.7%
1/15
|
|
Cardiac disorders
Cardiac Failure
|
6.7%
1/15
|
|
General disorders
Adverse Drug Reaction
|
6.7%
1/15
|
|
Hepatobiliary disorders
Ischaemic Hepatitis
|
6.7%
1/15
|
|
Infections and infestations
Arthritis Bacterial
|
6.7%
1/15
|
|
Infections and infestations
Bacteraemia
|
6.7%
1/15
|
|
Infections and infestations
Diverticulitis
|
6.7%
1/15
|
|
Infections and infestations
Endocarditis Bacterial
|
6.7%
1/15
|
|
Infections and infestations
Escherichia Bacteraemia
|
6.7%
1/15
|
|
Injury, poisoning and procedural complications
Femur Fracture
|
6.7%
1/15
|
|
Injury, poisoning and procedural complications
Humerus Fracture
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
Pathological Fracture
|
6.7%
1/15
|
|
Nervous system disorders
Embolic Stroke
|
6.7%
1/15
|
|
Vascular disorders
Hypotension
|
6.7%
1/15
|
Other adverse events
| Measure |
MRZ 0.5 mg/m^2
n=15 participants at risk
Twice-weekly dosing with 2-hour IV infusions on days 1,4,8, and 11 of 3-week cycles
|
|---|---|
|
General disorders
Fatigue
|
60.0%
9/15
|
|
General disorders
Oedema peripheral
|
6.7%
1/15
|
|
General disorders
Pyrexia
|
6.7%
1/15
|
|
General disorders
Asthenia
|
6.7%
1/15
|
|
General disorders
Chills
|
6.7%
1/15
|
|
General disorders
Gait disturbance
|
13.3%
2/15
|
|
Gastrointestinal disorders
Vomiting
|
13.3%
2/15
|
|
Gastrointestinal disorders
Constipation
|
20.0%
3/15
|
|
Psychiatric disorders
Hallucination, Visual
|
6.7%
1/15
|
|
Psychiatric disorders
Mental status changes
|
6.7%
1/15
|
|
Psychiatric disorders
Anxiety
|
20.0%
3/15
|
|
Infections and infestations
Upper respiratory tract infection
|
13.3%
2/15
|
|
Infections and infestations
Urinary tract infection
|
6.7%
1/15
|
|
Infections and infestations
Pneumonia
|
20.0%
3/15
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
13.3%
2/15
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
13.3%
2/15
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
13.3%
2/15
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
6.7%
1/15
|
|
Blood and lymphatic system disorders
Anaemia
|
26.7%
4/15
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
26.7%
4/15
|
|
Blood and lymphatic system disorders
Neutropenia
|
6.7%
1/15
|
|
Blood and lymphatic system disorders
Pancytopenia
|
6.7%
1/15
|
|
Cardiac disorders
Cardiac Failure Congestive
|
13.3%
2/15
|
|
Cardiac disorders
Atrial Fibrillation
|
6.7%
1/15
|
|
Cardiac disorders
Cardiac Failure
|
6.7%
1/15
|
|
Cardiac disorders
Sinus Tachycardia
|
6.7%
1/15
|
|
Cardiac disorders
Tachycardia
|
6.7%
1/15
|
|
Gastrointestinal disorders
Nausea
|
26.7%
4/15
|
|
Gastrointestinal disorders
Diarrhoea
|
13.3%
2/15
|
|
Gastrointestinal disorders
Abdominal Pain
|
6.7%
1/15
|
|
Gastrointestinal disorders
Abdominal Tenderness
|
6.7%
1/15
|
|
Gastrointestinal disorders
Dyspepsia
|
6.7%
1/15
|
|
Gastrointestinal disorders
Ileus
|
6.7%
1/15
|
|
Gastrointestinal disorders
Pneumoperitoneum
|
6.7%
1/15
|
|
General disorders
Adverse Drug Reaction
|
6.7%
1/15
|
|
General disorders
Infusion Site Erythema
|
6.7%
1/15
|
|
General disorders
Vessel Puncture Site Pain
|
6.7%
1/15
|
|
Hepatobiliary disorders
Ischaemic Hepatitis
|
6.7%
1/15
|
|
Infections and infestations
Bacteraemia
|
13.3%
2/15
|
|
Infections and infestations
Arthritis Bacterial
|
6.7%
1/15
|
|
Infections and infestations
Diverticulitis
|
6.7%
1/15
|
|
Infections and infestations
Endocarditis Bacterial
|
6.7%
1/15
|
|
Infections and infestations
Escherichia Bacteraemia
|
6.7%
1/15
|
|
Infections and infestations
Nasopharyngitis
|
6.7%
1/15
|
|
Infections and infestations
Oral Candidiasis
|
6.7%
1/15
|
|
Infections and infestations
Respiratory Tract Infection
|
6.7%
1/15
|
|
Infections and infestations
Sepsis
|
6.7%
1/15
|
|
Injury, poisoning and procedural complications
Contusion
|
6.7%
1/15
|
|
Injury, poisoning and procedural complications
Femur Fracture
|
6.7%
1/15
|
|
Injury, poisoning and procedural complications
Humerus Fracture
|
6.7%
1/15
|
|
Investigations
Blood Creatinine Increased
|
13.3%
2/15
|
|
Investigations
Weight Decreased
|
13.3%
2/15
|
|
Investigations
International Normalised Ratio Increased
|
6.7%
1/15
|
|
Investigations
Neutrophil Count Decreased
|
6.7%
1/15
|
|
Investigations
Platelet Count Decreased
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
13.3%
2/15
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
13.3%
2/15
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Metabolic Acidosis
|
6.7%
1/15
|
|
Metabolism and nutrition disorders
Metabolic Alkalosis
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
Pain in Jaw
|
13.3%
2/15
|
|
Musculoskeletal and connective tissue disorders
Pathological Fracture
|
13.3%
2/15
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
Neck Pain
|
6.7%
1/15
|
|
Nervous system disorders
Dysgeusia
|
13.3%
2/15
|
|
Nervous system disorders
Aphasia
|
6.7%
1/15
|
|
Nervous system disorders
Dysarthria
|
6.7%
1/15
|
|
Nervous system disorders
Embolic Stroke
|
6.7%
1/15
|
|
Nervous system disorders
Head Discomfort
|
6.7%
1/15
|
|
Nervous system disorders
Memory Impairment
|
6.7%
1/15
|
|
Psychiatric disorders
Insomnia
|
33.3%
5/15
|
|
Psychiatric disorders
Confusional State
|
13.3%
2/15
|
|
Psychiatric disorders
Dysphoria
|
6.7%
1/15
|
|
Psychiatric disorders
Pressure of Speech
|
6.7%
1/15
|
|
Renal and urinary disorders
Renal Failure Acute
|
13.3%
2/15
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
20.0%
3/15
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia Aspiration
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
Productive Cough
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
Sinus Congestion
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Rash Pruritic
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Skin Mass
|
6.7%
1/15
|
|
Vascular disorders
Hypotension
|
6.7%
1/15
|
|
Vascular disorders
Phlebitis
|
6.7%
1/15
|
Additional Information
Associate Director of Clinical and Regulatory Operations
Triphase Accelerator
Phone: 858-295-4337
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place