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Phase 2 Clinical Trial of NPI-0052 in Patients With Relapsed or Relapsed/Refractory Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00461045
Recruitment Status : Completed
First Posted : April 17, 2007
Results First Posted : September 13, 2017
Last Update Posted : December 19, 2017
Sponsor:
Information provided by (Responsible Party):
Celgene

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Myeloma
Intervention Drug: MRZ 0.5 mg/m^2
Enrollment 15
Recruitment Details  
Pre-assignment Details  
Arm/Group Title MRZ 0.5 mg/m^2
Hide Arm/Group Description Twice-weekly dosing with 2-hour IV infusions on days 1,4,8, and 11 of 3-week cycles
Period Title: Overall Study
Started 15
Completed 15
Not Completed 0
Arm/Group Title MRZ 0.5 mg/m^2
Hide Arm/Group Description Twice-weekly dosing with 2-hour IV infusions on days 1,4,8, and 11 of 3-week cycles
Overall Number of Baseline Participants 15
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants
61.9  (8.02)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
Female
5
  33.3%
Male
10
  66.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
15
 100.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
American Indian or Alaska Native
0
   0.0%
Asian
2
  13.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
3
  20.0%
White
10
  66.7%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 15 participants
15
Baseline Height  
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 15 participants
170.97  (12.152)
Baseline Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 15 participants
77.27  (17.825)
Body Surface Area (BSA)  
Mean (Standard Deviation)
Unit of measure:  M^2
Number Analyzed 15 participants
1.893  (0.2629)
Fertility Status  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
Potential able to bear children
0
   0.0%
Surgically sterile
1
   6.7%
Post menopausal
4
  26.7%
Male
10
  66.7%
Karnofsky Performance Status (KPS) Score   [1] 
Mean (Full Range)
Unit of measure:  KPS Score
Number Analyzed 15 participants
87.3
(70.0 to 100.0)
[1]
Measure Description: KPS Score: 100=Normal, no complaints; 90=Able to carry on normal activity, minor signs or symptoms of disease; 80=Normal activity with effort; 70= Unable to carry on normal activity or perform active work, cares for self.
Time Since Initial Diagnosis  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants
5.2  (3.79)
Number of Relapses  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants
1 Relapse 0
2 Relapses 2
3 Relapses 2
>3 Relapses 11
1.Primary Outcome
Title Number of Patients Exhibiting a Given Overall Response as Determined by Investigator
Hide Description 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.
Time Frame Through study completion, an average of 6.09 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title MRZ 0.5 mg/m^2
Hide Arm/Group Description:
Twice-weekly dosing with 2-hour IV infusions on days 1,4,8, and 11 of 3-week cycles
Overall Number of Participants Analyzed 15
Measure Type: Number
Unit of Measure: participants
Stringent Complete Response (sCR) or better 0
Complete Response (CR) 0
Very Good Partial Response (VGPR) 0
Partial Response (PR) 0
Minimal Response (MR) 0
Stable Disease (SD) 4
Progressive Disease (PD) 9
Not Evaluated 2
2.Secondary Outcome
Title Duration of MRZ Treatment
Hide Description Duration of treatment is defined as the last dose date minus the first dose date of the dose cohort plus 1 expressed in weeks.
Time Frame Through study completion, an average of 6.09 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title MRZ 0.5 mg/m^2
Hide Arm/Group Description:
Twice-weekly dosing with 2-hour IV infusions on days 1,4,8, and 11 of 3-week cycles
Overall Number of Participants Analyzed 15
Mean (Standard Deviation)
Unit of Measure: weeks
6.09  (4.661)
3.Secondary Outcome
Title Number of Cycles of Marizomib (MRZ)
Hide Description [Not Specified]
Time Frame Through study completion, an average of 6.09 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title MRZ 0.5 mg/m^2
Hide Arm/Group Description:
Twice-weekly dosing with 2-hour IV infusions on days 1,4,8, and 11 of 3-week cycles
Overall Number of Participants Analyzed 15
Mean (Standard Deviation)
Unit of Measure: cycles
2.6  (1.45)
4.Secondary Outcome
Title Number of Patients Receiving Marizomib (MRZ) in Each Cycle
Hide Description A patient was counted in a cycle if the patient received at least one dose of study drug during the cycle.
Time Frame Through study completion, an average of 6.09 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title MRZ 0.5 mg/m^2
Hide Arm/Group Description:
Twice-weekly dosing with 2-hour IV infusions on days 1,4,8, and 11 of 3-week cycles
Overall Number of Participants Analyzed 15
Measure Type: Count of Participants
Unit of Measure: Participants
Cycle 1
15
 100.0%
Cycle 2
12
  80.0%
Cycle 3
6
  40.0%
Cycle 4
3
  20.0%
Cycle 5
2
  13.3%
Cycle 6
1
   6.7%
5.Secondary Outcome
Title Number of Patients With Treatment Emergent Adverse Events (TEAEs)
Hide Description

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.

Time Frame Through study completion, an average of 6.09 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title MRZ 0.5 mg/m^2
Hide Arm/Group Description:
Twice-weekly dosing with 2-hour IV infusions on days 1,4,8, and 11 of 3-week cycles
Overall Number of Participants Analyzed 15
Measure Type: Count of Participants
Unit of Measure: Participants
At least one TEAE
15
 100.0%
At least one treatment related TEAE
14
  93.3%
At least one NPI-0052 related TEAE
13
  86.7%
At least one grade ≥3 TEAE
12
  80.0%
At least one treatment related grade ≥3 TEAE
8
  53.3%
At least one NPI-0052 related grade ≥3 TEAE
5
  33.3%
At least one serious TEAE
7
  46.7%
At least one treatment related serious TEAE
4
  26.7%
At least one NPI-0052 related serious TEAE
1
   6.7%
6.Secondary Outcome
Title Number of Treatment Emergent Adverse Events (TEAEs)
Hide Description

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.

Time Frame Through study completion, an average of 6.09 weeks.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title MRZ 0.5 mg/m^2
Hide Arm/Group Description:
Twice-weekly dosing with 2-hour IV infusions on days 1,4,8, and 11 of 3-week cycles
Overall Number of Participants Analyzed 15
Measure Type: Number
Unit of Measure: TEAEs
Number of TEAEs 149
Number of treatment related TEAEs 73
Number of NPI-0052 related TEAEs 50
Number of grade ≥3 TEAEs 41
Number of treatment related grade ≥3 TEAEs 16
Number of NPI-0052 realted grade ≥3 TEAEs 9
Number of serious TEAEs 21
Number of treatment related serious TEAEs 5
Number of NPI-0052 related serious TEAEs 1
7.Secondary Outcome
Title Maximum Observed Blood Drug Concentration (Cmax)
Hide Description [Not Specified]
Time Frame Samples collected on Cycle 1 Day 1 and Cycle 1 Day 11.
Hide Outcome Measure Data
Hide Analysis Population Description
The sponsor elected not to analyze the pharmacokinetic (PK) samples collected, therefore, no PK results are obtained.
Arm/Group Title MRZ 0.5 mg/m^2
Hide Arm/Group Description:
Twice-weekly dosing with 2-hour IV infusions on days 1,4,8, and 11 of 3-week cycles
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title MRZ 0.5 mg/m^2
Hide Arm/Group Description Twice-weekly dosing with 2-hour IV infusions on days 1,4,8, and 11 of 3-week cycles
All-Cause Mortality
MRZ 0.5 mg/m^2
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
MRZ 0.5 mg/m^2
Affected / at Risk (%)
Total   7/15 (46.67%) 
Cardiac disorders   
Cardiac Failure Congestive  1  2/15 (13.33%) 
Atrial Fibrillation  1  1/15 (6.67%) 
Cardiac Failure  1  1/15 (6.67%) 
General disorders   
Adverse Drug Reaction  1  1/15 (6.67%) 
Hepatobiliary disorders   
Ischaemic Hepatitis  1  1/15 (6.67%) 
Infections and infestations   
Sepsis  1  1/15 (6.67%) 
Pneumonia  1  1/15 (6.67%) 
Arthritis Bacterial  1  1/15 (6.67%) 
Bacteraemia  1  1/15 (6.67%) 
Diverticulitis  1  1/15 (6.67%) 
Endocarditis Bacterial  1  1/15 (6.67%) 
Escherichia Bacteraemia  1  1/15 (6.67%) 
Injury, poisoning and procedural complications   
Femur Fracture  1  1/15 (6.67%) 
Humerus Fracture  1  1/15 (6.67%) 
Metabolism and nutrition disorders   
Hyperglycaemia  1  1/15 (6.67%) 
Musculoskeletal and connective tissue disorders   
Pathological Fracture  1  1/15 (6.67%) 
Nervous system disorders   
Embolic Stroke  1  1/15 (6.67%) 
Renal and urinary disorders   
Renal failure acute  1  2/15 (13.33%) 
Vascular disorders   
Hypotension  1  1/15 (6.67%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (8.1)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
MRZ 0.5 mg/m^2
Affected / at Risk (%)
Total   15/15 (100.00%) 
Blood and lymphatic system disorders   
Anaemia  1  4/15 (26.67%) 
Thrombocytopenia  1  4/15 (26.67%) 
Neutropenia  1  1/15 (6.67%) 
Pancytopenia  1  1/15 (6.67%) 
Cardiac disorders   
Cardiac Failure Congestive  1  2/15 (13.33%) 
Atrial Fibrillation  1  1/15 (6.67%) 
Cardiac Failure  1  1/15 (6.67%) 
Sinus Tachycardia  1  1/15 (6.67%) 
Tachycardia  1  1/15 (6.67%) 
Gastrointestinal disorders   
Vomiting  1  2/15 (13.33%) 
Constipation  1  3/15 (20.00%) 
Nausea  1  4/15 (26.67%) 
Diarrhoea  1  2/15 (13.33%) 
Abdominal Pain  1  1/15 (6.67%) 
Abdominal Tenderness  1  1/15 (6.67%) 
Dyspepsia  1  1/15 (6.67%) 
Ileus  1  1/15 (6.67%) 
Pneumoperitoneum  1  1/15 (6.67%) 
General disorders   
Fatigue  1  9/15 (60.00%) 
Oedema peripheral  1  1/15 (6.67%) 
Pyrexia  1  1/15 (6.67%) 
Asthenia  1  1/15 (6.67%) 
Chills  1  1/15 (6.67%) 
Gait disturbance  1  2/15 (13.33%) 
Adverse Drug Reaction  1  1/15 (6.67%) 
Infusion Site Erythema  1  1/15 (6.67%) 
Vessel Puncture Site Pain  1  1/15 (6.67%) 
Hepatobiliary disorders   
Ischaemic Hepatitis  1  1/15 (6.67%) 
Infections and infestations   
Upper respiratory tract infection  1  2/15 (13.33%) 
Urinary tract infection  1  1/15 (6.67%) 
Pneumonia  1  3/15 (20.00%) 
Bacteraemia  1  2/15 (13.33%) 
Arthritis Bacterial  1  1/15 (6.67%) 
Diverticulitis  1  1/15 (6.67%) 
Endocarditis Bacterial  1  1/15 (6.67%) 
Escherichia Bacteraemia  1  1/15 (6.67%) 
Nasopharyngitis  1  1/15 (6.67%) 
Oral Candidiasis  1  1/15 (6.67%) 
Respiratory Tract Infection  1  1/15 (6.67%) 
Sepsis  1  1/15 (6.67%) 
Injury, poisoning and procedural complications   
Contusion  1  1/15 (6.67%) 
Femur Fracture  1  1/15 (6.67%) 
Humerus Fracture  1  1/15 (6.67%) 
Investigations   
Blood Creatinine Increased  1  2/15 (13.33%) 
Weight Decreased  1  2/15 (13.33%) 
International Normalised Ratio Increased  1  1/15 (6.67%) 
Neutrophil Count Decreased  1  1/15 (6.67%) 
Platelet Count Decreased  1  1/15 (6.67%) 
Metabolism and nutrition disorders   
Hyperglycaemia  1  2/15 (13.33%) 
Hypokalaemia  1  2/15 (13.33%) 
Decreased Appetite  1  1/15 (6.67%) 
Hyperuricaemia  1  1/15 (6.67%) 
Hypomagnesaemia  1  1/15 (6.67%) 
Hyponatraemia  1  1/15 (6.67%) 
Metabolic Acidosis  1  1/15 (6.67%) 
Metabolic Alkalosis  1  1/15 (6.67%) 
Musculoskeletal and connective tissue disorders   
Pain in extremity  1  2/15 (13.33%) 
Back pain  1  2/15 (13.33%) 
Arthralgia  1  2/15 (13.33%) 
Muscle spasms  1  1/15 (6.67%) 
Pain in Jaw  1  2/15 (13.33%) 
Pathological Fracture  1  2/15 (13.33%) 
Musculoskeletal Pain  1  1/15 (6.67%) 
Neck Pain  1  1/15 (6.67%) 
Nervous system disorders   
Dysgeusia  1  2/15 (13.33%) 
Aphasia  1  1/15 (6.67%) 
Dysarthria  1  1/15 (6.67%) 
Embolic Stroke  1  1/15 (6.67%) 
Head Discomfort  1  1/15 (6.67%) 
Memory Impairment  1  1/15 (6.67%) 
Psychiatric disorders   
Hallucination, Visual  1  1/15 (6.67%) 
Mental status changes  1  1/15 (6.67%) 
Anxiety  1  3/15 (20.00%) 
Insomnia  1  5/15 (33.33%) 
Confusional State  1  2/15 (13.33%) 
Dysphoria  1  1/15 (6.67%) 
Pressure of Speech  1  1/15 (6.67%) 
Renal and urinary disorders   
Renal Failure Acute  1  2/15 (13.33%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  3/15 (20.00%) 
Asthma  1  1/15 (6.67%) 
Cough  1  1/15 (6.67%) 
Epistaxis  1  1/15 (6.67%) 
Pneumonia Aspiration  1  1/15 (6.67%) 
Productive Cough  1  1/15 (6.67%) 
Rhinorrhoea  1  1/15 (6.67%) 
Sinus Congestion  1  1/15 (6.67%) 
Skin and subcutaneous tissue disorders   
Rash  1  1/15 (6.67%) 
Rash Pruritic  1  1/15 (6.67%) 
Skin Mass  1  1/15 (6.67%) 
Vascular disorders   
Hypotension  1  1/15 (6.67%) 
Phlebitis  1  1/15 (6.67%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (8.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Associate Director of Clinical and Regulatory Operations
Organization: Triphase Accelerator
Phone: 858-295-4337
EMail: jennifer.ki@triphaseco.com
Publications:
Cheson BD, Pfistner B, Juweid ME, et al. Revised Response Criteria for Malignant Lymphomas. From the Members of the International Harmonization Project (IHP) of the Competence Network Malignant Lymphoma, 47th Annual Meeting of the American Society of Hematology. Blood. 2005 Nov;106: abstract #18
ClinicalTrials.gov. Phase 3 Study With Carfilzomib and Dexamethasone Versus Velcade and Dexamethasone for Relapsed Multiple Myeloma Patients (ENDEAVOR). ClinicalTrials.gov Identifier: NCT01568866.
12. Facon T, Dimopoulos M, Dispenzieri A, et al. Initial Phase 3 Results Of The First (Frontline Investigation Of Lenalidomide + Dexamethasone Versus Standard Thalidomide) Trial (MM-020/IFM 07 01) In Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts) Ineligible For Stem Cell Transplantation (SCT). 2013; ASH Annual Meeting Plenary Session, Sunday, December 8, 2013: 2:55 PM
KYPROLIS™ (carfilzomib) for Injection Prescribing Information. Onyx Pharmaceuticals, Inc., South San Francisco, CA; 07/2012. http://www.kyprolis.com/Areas/Hcp/content/pdfs/PI.pdf
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. http://www.cap.org/apps/docs/committees/immunology/myeloma.pdf. Multiple Myeloma (V.1.2011), 201. Accessed 20 September 2013
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. http://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. Multiple Myeloma (Version 2.2013). Accessed 29 August 2013
Suzuki E, Jazirehi A, Palladino M, Bonavida B. Chemosensitization of Drug and Rituximab Resistant Daudi B-NHL Clones to Drug-Induced Apoptosis by the Proteasome Inhibitor NPI-0052. 47th Annual Meeting of the American Society for Hematology. Blood. 2005;106: abstract #1521
Layout table for additonal information
Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT00461045    
Other Study ID Numbers: NPI-0052-101
First Submitted: April 13, 2007
First Posted: April 17, 2007
Results First Submitted: March 29, 2017
Results First Posted: September 13, 2017
Last Update Posted: December 19, 2017