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

NCT02103335 | Completed Phase 1

• 1 other identifier: NPI-0052-107
• Study Type: interventional
• Target: 38
• Locations: 2 countries
• Sites: 6

Brief Summary

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.

Conditions

Multiple Myeloma in Relapse; Refractory Multiple Myeloma; Multiple Myeloma

Keywords

Myeloma; Multiple Myeloma; Pomalidomide; Marizomib; Low dose Dexamethasone; Relapsed; Refractory

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose and/or recommended Phase 2 dose

  Continuous up to one year

Secondary Outcomes (2)

• Adverse events

  Up to 5 years

• Response rate

  Up to 5 years

Study Arms (1)

Single Group Assignment

EXPERIMENTAL

Combination Pomalidomide, low-dose Dexamethasone, and Marizomib:

Drug: pomalidomide; Drug: marizomib; Drug: low-dose dexamethasone

Interventions

pomalidomide DRUG

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

Also known as: POMALYST

Single Group Assignment

marizomib DRUG

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

Also known as: NPI-0052

Single Group Assignment

low-dose dexamethasone DRUG

Oral Dexamethasone, days 1, 2, 4, 5, 8, 9, 11, 12, 15, 16, 22, 23 of 28 day cycle, 5 or 10 mg

Single Group Assignment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must meet the following criteria to be eligible for study participation:
• At least 18 years at the time of signing the informed consent form.
• Able to understand and voluntarily sign an informed consent form prior to any study-related assessments/procedures.
• Able to adhere to the study visit schedule and other protocol requirements.
• 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.
• Previously received 1 or more lines of anti-myeloma therapy that must have included both lenalidomide and bortezomib (either separately or in combination).
• Documented disease progression during or within 60 days after their most recent line of anti myeloma therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status score ≤2.
• 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.
• 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.
• All study participants outside the USA must agree to comply with the POMALYST® PPRMP requirements.
• 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).
• 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.
• For all females: Agree to abstain from breastfeeding during study participation and for at least 28 days after study treatment discontinuation.
• 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.

You may not qualify if:

• Subjects with any of the following will be excluded from participation in the study:
• Peripheral neuropathy Grade ≥2.
• Non-secretory multiple myeloma.
• 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).
• 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;

Sponsors & Collaborators

• Celgene: lead
• Celgene Corporation: collaborator

Study Sites (6)

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

University of Maryland

Baltimore, Maryland, 20201, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

Peter MacCallum Cancer Centre

East Melbourne, Victoria, 3002, Australia

Location

Alfred Hospital

Prahran, Victoria, 3181, Australia

Location

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  BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell; Recurrence

Interventions

pomalidomide; marizomib; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Steven D Reich, MD

  Triphase Research and Development I Corp

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2014
• First Posted: April 3, 2014
• Study Start: June 5, 2014
• Primary Completion: October 3, 2016
• Study Completion: November 30, 2016
• Last Updated: November 22, 2017

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); AU (2)