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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02103335




Registration number
NCT02103335
Ethics application status
Date submitted
27/03/2014
Date registered
3/04/2014

Titles & IDs
Public title
Combination Study of Pomalidomide, Marizomib, and Low-Dose Dexamethasone in Relapsed and Refractory Multiple Myeloma
Scientific title
A Phase 1, Multicenter, Open-label, Dose-Escalation Combination Study of Pomalidomide, Marizomib, and Low-Dose Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma
Secondary ID [1] 0 0
NPI-0052-107
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma in Relapse 0 0
Refractory Multiple Myeloma 0 0
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - pomalidomide
Treatment: Drugs - marizomib
Treatment: Drugs - low-dose dexamethasone

Experimental: Single Group Assignment - Combination Pomalidomide, low-dose Dexamethasone, and Marizomib:


Treatment: Drugs: pomalidomide
Oral Pomalidomide, days 1-21 of 28 day cycle, dose 3 to 4 mg

Treatment: Drugs: marizomib
IV Marizomib, 0.2 to 0.5 mg/m2 on days 1, 4, 8, 11 of 28 day cycle

Treatment: Drugs: low-dose dexamethasone
Oral Dexamethasone, days 1, 2, 4, 5, 8, 9, 11, 12, 15, 16, 22, 23 of 28 day cycle, 5 or 10 mg
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum tolerated dose and/or recommended Phase 2 dose
Timepoint [1] 0 0
Continuous up to one year
Secondary outcome [1] 0 0
Adverse events
Timepoint [1] 0 0
Up to 5 years
Secondary outcome [2] 0 0
Response rate
Timepoint [2] 0 0
Up to 5 years

Eligibility
Key inclusion criteria
Inclusion Criteria

Subjects must meet the following criteria to be eligible for study participation:

1. At least 18 years at the time of signing the informed consent form.
2. Able to understand and voluntarily sign an informed consent form prior to any study-related assessments/procedures.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Documented diagnosis of multiple myeloma and measurable disease by serum or urine protein electrophoresis (SPEP or UPEP): SPEP =0.5 g/dL, UPEP =200 mg/24 hours, or involved serum free light chain (FLC) level =10 mg/dL provided the serum FLC ratio is abnormal.
5. Previously received 1 or more lines of anti-myeloma therapy that must have included both lenalidomide and bortezomib (either separately or in combination).
6. Documented disease progression during or within 60 days after their most recent line of anti myeloma therapy.
7. Eastern Cooperative Oncology Group (ECOG) performance status score =2.
8. All study participants in the USA must be registered into the mandatory POMALYST REMS™ (Risk Evaluation & Mitigation Strategy) program, and be willing and able to comply with the requirements of the POMALYST REMS™ program.
9. All study participants in the USA who are females of child-bearing potential (FCBP) must adhere to the scheduled pregnancy testing as required in the POMALYST REMS™ program.
10. All study participants outside the USA must agree to comply with the POMALYST® PPRMP requirements.
11. All subjects must be able and agree to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).
12. For females of child bearing potential (FCBP): Agree to use 2 reliable forms of contraception simultaneously or practice complete abstinence from heterosexual contact for at least 28 days before starting study treatment, while participating in the study (including dose interruptions), and for at least 28 days after study treatment discontinuation; must follow pregnancy testing requirements as outlined in the POMALYST REMS™ program or the PPRMP.
13. For all females: Agree to abstain from breastfeeding during study participation and for at least 28 days after study treatment discontinuation.
14. For all males: Agree to use a latex or synthetic condom during any sexual contact with FCBP while participating in the study and for at least 28 days following discontinuation from study treatment, even if he has undergone a successful vasectomy.
15. For all males: Agree to refrain from donating semen or sperm while on study and for at least 28 days after discontinuation from study treatment.
16. Refrain from donating blood while on study treatment and for at least 28 days after discontinuation from study treatment.
17. Agree not to share medication.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

Subjects with any of the following will be excluded from participation in the study:

1. Peripheral neuropathy Grade =2.
2. Non-secretory multiple myeloma.
3. Any of the following laboratory abnormalities:

* ANC <1,000/µL;
* Platelet count <50,000/µL for subjects in whom <50% of bone marrow nucleated cells are plasma cells; or a platelet count <30,000/µL for subjects in whom =50% of bone marrow nucleated cells are plasma cells;
* Creatinine clearance (CrCL) <45 mL/min as measured directly or as calculated according to Cockcroft Gault formula;
* Corrected serum calcium >13.5 mg/dL (>3.4 mmol/L);
* Hemoglobin <8 g/dL (<4.9 mmol/L; prior red blood cell [RBC] transfusion or recombinant human erythropoietin use is permitted before study entry);
* Serum aspartate aminotransferase (AST) >3.0 x upper limit of normal (ULN);
* Serum alanine aminotransferase (ALT) >3.0 x ULN;
* Serum total bilirubin >1.5 x ULN (>3.0 x ULN for subjects with known Gilbert's disease).
4. Prior history of malignancies, other than MM, unless the subject has been free of the disease for =5 years. Subjects may be entered earlier than 5 years if they have received curative treatment for the following:

* Basal cell carcinoma of the skin;
* Squamous cell carcinoma of the skin;
* Carcinoma in situ of the cervix;
* Carcinoma in situ of the breast;

Or if they have:

o Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or non metastatic prostate cancer that is in complete remission or does not require treatment.
5. Previous therapy with POM and/or MRZ.
6. History of allergic reaction or hypersensitivity to thalidomide, lenalidomide, bortezomib, carfilzomib, boron, mannitol, or DEX.
7. Grade =3 rash during prior thalidomide or lenalidomide therapy.
8. Gastrointestinal disease that may significantly alter the absorption of POM.
9. History of the following:

* Congestive heart failure of Class III or IV of the New York Heart Association (NYHA) classification;
* Myocardial infarction within 12 months prior to starting study treatment;
* Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris.
10. Any of the following within 14 days prior to initiation of study treatment:

* Plasmapheresis;
* Major surgery (kyphoplasty is not considered major surgery);
* Radiation therapy;
* Anti-myeloma drug therapy.
11. Received any investigational agents within 28 days or 5 half-lives (whichever is longer) prior to initiation of study treatment.
12. Conditions requiring chronic steroid or immunosuppressive treatment (eg, rheumatoid arthritis, multiple sclerosis, or lupus), which likely need additional steroid or immunosuppressive treatments in addition to the study treatment.
13. Subjects may not receive corticosteroids (>10 mg/day of prednisone or equivalent) within 3 weeks prior to enrollment (use of steroidal inhalation aerosol for asthma is permitted).
14. Unable or unwilling to undergo antithrombotic prophylactic treatment.
15. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study, as determined by the Investigator.
16. Pregnant and/or breastfeeding females.
17. Known seropositive for or active viral infection with human immunodeficiency virus (HIV).
18. Known seropositive for or active viral infection with hepatitis B virus (HBV), with the following exceptions:

* negative are eligible.
* Subjects who had hepatitis B but have received an antiviral treatment and show non-detectable viral DNA for 6 months are eligible.
* Subjects who are seropositive because of hepatitis B virus vaccine are eligible.
19. Known seropositive for or active viral infection with hepatitis C virus (HCV), with the following exception: Subjects who had hepatitis C but have received an antiviral treatment and show no detectable viral ribonucleic acid (RNA) for 6 months are eligible.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/06/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/11/2016
Sample size
Target
Accrual to date
Final
38
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - East Melbourne
Recruitment hospital [2] 0 0
Alfred Hospital - Prahran
Recruitment postcode(s) [1] 0 0
3002 - East Melbourne
Recruitment postcode(s) [2] 0 0
3181 - Prahran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Illinois
Country [2] 0 0
United States of America
State/province [2] 0 0
Maryland
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Celgene
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Celgene Corporation
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Steven D Reich, MD
Address 0 0
Triphase Research and Development I Corp
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02103335