AzTrials
AzTrials

Multiple Myeloma in RelapsePhase 1NCT02103335

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

A Phase 1 study testing pomalidomide, marizomib and low-dose dexamethasone in people with Multiple Myeloma in Relapse and Refractory Multiple Myeloma, run by Celgene at 6 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
pomalidomide, marizomib and low-dose dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
6 sitesin 2 countries
Study dates
5 Jun 2014to 30 Nov 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
Show all 18Show fewer
  • 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.
  • 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.
  • Refrain from donating blood while on study treatment and for at least 28 days after discontinuation from study treatment.
  • Agree not to share medication.

Who cannot join

  • 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;
Show all 44Show fewer
  • 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;
  • 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.
  • Previous therapy with POM and/or MRZ.
  • History of allergic reaction or hypersensitivity to thalidomide, lenalidomide, bortezomib, carfilzomib, boron, mannitol, or DEX.
  • Grade ≥3 rash during prior thalidomide or lenalidomide therapy.
  • Gastrointestinal disease that may significantly alter the absorption of POM.
  • 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.
  • 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.
  • Received any investigational agents within 28 days or 5 half-lives (whichever is longer) prior to initiation of study treatment.
  • 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.
  • 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).
  • Unable or unwilling to undergo antithrombotic prophylactic treatment.
  • 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.
  • Pregnant and/or breastfeeding females.
  • Known seropositive for or active viral infection with human immunodeficiency virus (HIV).
  • 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.
  • 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.

Trial locations and contacts

6 sites in 2 countries.

6 sites in 2 countries

United States4 sites

  • University of Maryland

    Baltimore, Maryland, 20201

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Karmanos Cancer Center

    Detroit, Michigan, 48201

Other trials in United States

Australia2 sites

  • Peter MacCallum Cancer Centre

    East Melbourne, Victoria, 3002

  • Alfred Hospital

    Prahran, Victoria, 3181

Other trials in Australia

About this study

Official 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

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.
Read more

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.

Being tested
pomalidomide, marizomib, low-dose dexamethasone
Keywords
Myeloma, Multiple Myeloma, Pomalidomide, Marizomib, Low dose Dexamethasone, Relapsed, Refractory
Medical subject headings
Multiple Myeloma, Neoplasms, Plasma Cell, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • pomalidomideDrug

    Also called POMALYST

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

  • marizomibDrug

    Also called NPI-0052

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

  • low-dose dexamethasoneDrug

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

Study groups in NCT02103335
Study groupRoleWhat they receive
Single Group AssignmentExperimentalCombination Pomalidomide, low-dose Dexamethasone, and Marizomib:
Receives: Drug: pomalidomide; Drug: marizomib; Drug: low-dose dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose and/or recommended Phase 2 dose

    Measured: Continuous up to one year

Secondary outcomes (2)

  1. Adverse events

    Measured: Up to 5 years

  2. Response rate

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Apr 2014 (estimated)
  2. Study start5 Jun 2014
  3. Primary completion3 Oct 2016
  4. Study completion30 Nov 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02103335
Sponsor's protocol ID
NPI-0052-107
Status last verified
Nov 2017
First submitted
27 Mar 2014
Last updated
22 Nov 2017
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Chauhan D, Li G, Shringarpure R, Podar K, Ohtake Y, Hideshima T, Anderson KC. Blockade of Hsp27 overcomes Bortezomib/proteasome inhibitor PS-341 resistance in lymphoma cells. Cancer Res. 2003 Oct 1;63(19):6174-7.

    PubMed 14559800

  • Chauhan D, Singh AV, Ciccarelli B, Richardson PG, Palladino MA, Anderson KC. Combination of novel proteasome inhibitor NPI-0052 and lenalidomide trigger in vitro and in vivo synergistic cytotoxicity in multiple myeloma. Blood. 2010 Jan 28;115(4):834-45. doi: 10.1182/blood-2009-03-213009. Epub 2009 Nov 13.

    PubMed 19965674

  • Child JA, Morgan GJ, Davies FE, Owen RG, Bell SE, Hawkins K, Brown J, Drayson MT, Selby PJ; Medical Research Council Adult Leukaemia Working Party. High-dose chemotherapy with hematopoietic stem-cell rescue for multiple myeloma. N Engl J Med. 2003 May 8;348(19):1875-83. doi: 10.1056/NEJMoa022340.

    PubMed 12736280

  • Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41. doi: 10.1159/000180580.

    PubMed 1244564

  • Dexamethasone Prescribing Information. Roxane Laboratories Inc., Columbus, OH; Sep 2007. http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase= renetnt&folderPath=/Prescribing+Information/PIs/Roxane/Dexamethasone/Dexamethasone+Tablets+Solution+and+Intensol.pdf. Accessed 20 September 2013.

  • Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A, San Miguel J, Hellmann A, Facon T, Foa R, Corso A, Masliak Z, Olesnyckyj M, Yu Z, Patin J, Zeldis JB, Knight RD; Multiple Myeloma (010) Study Investigators. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007 Nov 22;357(21):2123-32. doi: 10.1056/NEJMoa070594.

    PubMed 18032762

  • Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K, Gertz M, Dimopoulos M, Westin J, Sonneveld P, Ludwig H, Gahrton G, Beksac M, Crowley J, Belch A, Boccadaro M, Cavo M, Turesson I, Joshua D, Vesole D, Kyle R, Alexanian R, Tricot G, Attal M, Merlini G, Powles R, Richardson P, Shimizu K, Tosi P, Morgan G, Rajkumar SV; International Myeloma Working Group. International uniform response criteria for multiple myeloma. Leukemia. 2006 Sep;20(9):1467-73. doi: 10.1038/sj.leu.2404284. Epub 2006 Jul 20.

    PubMed 16855634

  • Fermand JP, Katsahian S, Divine M, Leblond V, Dreyfus F, Macro M, Arnulf B, Royer B, Mariette X, Pertuiset E, Belanger C, Janvier M, Chevret S, Brouet JC, Ravaud P; Group Myelome-Autogreffe. High-dose therapy and autologous blood stem-cell transplantation compared with conventional treatment in myeloma patients aged 55 to 65 years: long-term results of a randomized control trial from the Group Myelome-Autogreffe. J Clin Oncol. 2005 Dec 20;23(36):9227-33. doi: 10.1200/JCO.2005.03.0551. Epub 2005 Nov 7.

    PubMed 16275936

  • Hideshima T, Chauhan D, Shima Y, Raje N, Davies FE, Tai YT, Treon SP, Lin B, Schlossman RL, Richardson P, Muller G, Stirling DI, Anderson KC. Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy. Blood. 2000 Nov 1;96(9):2943-50.

    PubMed 11049970

  • Howlader N, Noone AM, Krapcho M, et al. (eds). SEER Cancer Statistics Review, 1975 2009 (Vintage 2009 Populations), National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2009_pops09/. Accessed 20 September 2013.

  • Kastritis E, Charidimou A, Varkaris A, Dimopoulos MA. Targeted therapies in multiple myeloma. Target Oncol. 2009 Jan;4(1):23-36. doi: 10.1007/s11523-008-0102-9. Epub 2009 Jan 17.

    PubMed 19343299

  • Kline JA, Wells PS. Methodology for a rapid protocol to rule out pulmonary embolism in the emergency department. Ann Emerg Med. 2003 Aug;42(2):266-75. doi: 10.1067/mem.2003.268.

    PubMed 12883516

  • Miguel JS, Weisel K, Moreau P, Lacy M, Song K, Delforge M, Karlin L, Goldschmidt H, Banos A, Oriol A, Alegre A, Chen C, Cavo M, Garderet L, Ivanova V, Martinez-Lopez J, Belch A, Palumbo A, Schey S, Sonneveld P, Yu X, Sternas L, Jacques C, Zaki M, Dimopoulos M. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013 Oct;14(11):1055-1066. doi: 10.1016/S1470-2045(13)70380-2. Epub 2013 Sep 3.

    PubMed 24007748

  • Mitsiades N, Mitsiades CS, Poulaki V, Chauhan D, Richardson PG, Hideshima T, Munshi NC, Treon SP, Anderson KC. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood. 2002 Jun 15;99(12):4525-30. doi: 10.1182/blood.v99.12.4525.

    PubMed 12036884

  • 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.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing pomalidomide, marizomib and low-dose dexamethasone in people with Multiple Myeloma in Relapse and Refractory Multiple Myeloma, run by Celgene at 6 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 44 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose and/or recommended Phase 2 dose (time frame: Continuous up to one year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02103335, which also lists 25 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in