Combination Study of Pomalidomide, Marizomib, and Low-Dose Dexamethasone in Relapsed and Refractory Multiple Myeloma

November 20, 2017 updated by: Celgene

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

This is a Phase 1 clinical trial to evaluate a new combination of drugs for the treatment of relapsed or refractory (drug-resistant) multiple myeloma. The drugs being studied are:

  • Pomalidomide (POMALYST®) is a drug that affects the immune system (an immunomodulatory drug) that has been approved by the United States (US) Food and Drug Administration (FDA) for the treatment of multiple myeloma.
  • Marizomib is an investigational drug being developed by Triphase that is being studied for the treatment of multiple myeloma. Investigational drugs are drugs that have not yet been approved by health authorities, such as the FDA, for general use but have been approved for use in specific clinical studies. Marizomib inhibits a cellular machine called the proteasome, which destroys unnecessary or damaged proteins. Other proteasome inhibitors have been shown to be effective in the treatment of multiple myeloma.
  • Dexamethasone is a corticosteroid drug that affects the immune system (an immunomodulatory drug) that has been approved by the FDA for the treatment of multiple myeloma.

This is the first study to evaluate the three-drug combination of pomalidomide (POM), marizomib (MRZ), and dexamethasone (LD-DEX) in humans. Pomalidomide, alone or in combination with dexamethasone, is approved by the FDA for the treatment of relapsed or refractory multiple myeloma.

The primary objective of this study is to determine the best drug dosing levels for this three-drug combination, including the highest safe doses and/or the recommended doses for future clinical studies of this drug combination. The secondary purposes of this study are to determine the safety of this drug combination and its effectiveness in treating relapsed or refractory multiple myeloma. The study will include examination of levels of all three drugs in the blood during various time points during treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

38

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • East Melbourne, Victoria, Australia, 3002
        • Peter MacCallum Cancer Centre
      • Prahran, Victoria, Australia, 3181
        • Alfred Hospital
  • United States
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 20201
        • University of Maryland
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single Group Assignment
Combination Pomalidomide, low-dose Dexamethasone, and Marizomib:
Drug: pomalidomide
Oral Pomalidomide, days 1-21 of 28 day cycle, dose 3 to 4 mg
Other Names:
  • POMALYST
Drug: marizomib
IV Marizomib, 0.2 to 0.5 mg/m2 on days 1, 4, 8, 11 of 28 day cycle
Other Names:
  • NPI-0052
Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose and/or recommended Phase 2 dose
Time Frame: Continuous up to one year
Continuous up to one year

Secondary Outcome Measures

Outcome Measure
Time Frame
Response rate
Time Frame: Up to 5 years
Up to 5 years
Adverse events
Time Frame: Up to 5 years
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Celgene

Collaborators

Celgene Corporation

Investigators

  • Study Director: Steven D Reich, MD, Triphase Research and Development I Corp

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 5, 2014

Primary Completion (Actual)

October 3, 2016

Study Completion (Actual)

November 30, 2016

Study Registration Dates

First Submitted

March 27, 2014

First Submitted That Met QC Criteria

March 31, 2014

First Posted (Estimate)

April 3, 2014

Study Record Updates

Last Update Posted (Actual)

November 22, 2017

Last Update Submitted That Met QC Criteria

November 20, 2017

Last Verified

November 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NPI-0052-107

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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