Study to Investigate the Safety and Effectiveness of Two Doses of the Antibody Drug GSK2857916 in Relapsed/Refractory Multiple Myeloma Patients

Overview

  • Study type

    Interventional
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • Site IRB
    • Scottsdale/Phoenix, Arizona: 18-005040
    • Jacksonville, Florida: 18-005040
    • Rochester, Minnesota: 18-005040
    NCT ID: NCT03525678
    Sponsor Protocol Number: 205678

About this study

The purpose of this study is to investigate the safety and effectiveness of two doses of the antibody drug GSK2857916 in multiple myeloma patients who had 3 or more prior lines of treatment, are refractory to a proteasome inhibitor and an immunomodulatory agent and have failed an Anti-CD38 Antibody (DREAMM 2).

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria:

  • Subjects provide signed written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
  • Male or female, 18 years or older.
  • Subjects with Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • Histologically or cytologically confirmed diagnosis of MM as defined according to International Myeloma Working Group (IMWG). The subject has undergone stem cell transplant or is considered transplant ineligible and has failed at least 3 prior lines of anti-myeloma treatments, including an anti-CD38 antibody (example [e.g.], daratumumab) alone or in combination, and is refractory to an Immunomodulatory drugs (IMiD) (that is [e.g.], lenalidomide or pomalidomide), and to a proteasome inhibitor (e.g., bortezomib, ixazomib or carfilzomib).
  • The subject has measurable disease with at least one of the following:
    • Serum M-protein >=0.5 gram per deciliter (g/dL) (>=5 gram per Liter [g/L]); Urine M-protein >=200 milligram per 24 hours (mg/24h);
    • Serum Free light chain (FLC) assay:
      • Involved FLC level >=10 mg/dL (>=100 mg/L) and an abnormal serum free light chain ratio (<0.26 or >1.65).
  • Subjects with a history of autologous stem cell transplant are eligible for study participation provided the following eligibility criteria are met:
    • Transplant was >100 days prior to study enrolment; no active infection(s); subjects meets the remainder of the eligibility criteria outlined in this protocol.
  • Subjects with adequate organ system functions as defined follows:
    • Absolute neutrophil count (ANC) >=1.0 X 10^9/L;
    • Hemoglobin >=8.0 g/dL;
    • Platelets>= 50 X 10^9/L;
    • Total bilirubin <=1.5X Upper limit of normal (ULN). Isolated bilirubin >=1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent);
    • Alanine aminotransferase (ALT) <=2.5X ULN;
    • Estimated glomerular filtration rate (eGFR) >=30 milliliter per minute per 1.73 meter square (mL/min/m^2);
    • Spot urine (albumin/creatinine ratios [spot urine]) < 500 milligram per gram (mg/g) (56 mg per millimoles [mg/mmol]);
    • Left ventricular ejection fraction (LVEF) >= 45 percent.
  • Female subjects:
    • Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. A female subject is eligible to participate if she is not pregnant or breastfeeding, and not a woman of childbearing potential (WOCBP) or is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency, during the intervention period and for at least 80 days after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. A WOCBP must have a negative highly sensitive serum pregnancy test (as required by local regulations) within 72 hours before the first dose of study intervention.
  • Male subjects are eligible to participate if they agree to the following during the intervention period and for at least 140 days:
    • Refrain from donating sperm;
    • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent;
    • Agree to use a male condom and female partner to use an additional highly effective contraceptive method with a failure rate of <1 percent per year as when having sexual intercourse with a woman of childbearing potential who is not currently pregnant.
  • All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.03, must be <=Grade 1 at the time of enrolment except for alopecia and Grade 2 peripheral neuropathy.
  • For France only: A subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

  • Systemic anti-myeloma therapy within <14 days, or plasmapheresis within 7 days prior to the first dose of study drug.
  • Symptomatic amyloidosis, active 'polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes' (POEMS) syndrome, active plasma cell leukemia at the time of screening.
  • Prior allogeneic stem cell transplant.
  • Current corneal epithelial disease except mild punctate keratopathy.
  • Use of an investigational drug within 14 days or five half-lives, whichever is shorter, preceding the first dose of study drug. Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs. Prior BCMA targeted therapy.
  • Evidence of active mucosal or internal bleeding.
  • Any major surgery within the last four weeks.
  • Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect subject's safety). Subjects with isolated proteinuria resulting from MM are eligible.
  • Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including lab abnormalities) that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures.
  • Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Stable chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if subject otherwise meets entry criteria.
  • Malignancies other than disease under study are excluded, except for any other malignancy from which the subject has been disease-free for more than 2 years and, in the opinion of the principal investigators and GSK Medical Monitor, will not affect the evaluation of the effects of this clinical trial treatment on the currently targeted malignancy (MM).
  • Evidence of cardiovascular risk including any of the following:
    • Corrected QT interval Fridericia (QTcF) interval >=470 milliseconds (msecs);
    • Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Type II) or 3rd degree atrioventricular (AV) block;
    • History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within six months of Screening;
    • Class III or IV heart failure as defined by the New York Heart Association functional classification system (NYHA);
    • Uncontrolled hypertension.
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GSK2857916, or any of the components of the study treatment.
  • Pregnant or lactating female.
  • Active infection requiring antibiotic, antiviral, or antifungal treatment.
  • Known Human Immunodeficiency Virus (HIV) infection.
  • Presence of hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb at screening or within 3 months prior to first dose of study treatment.
  • Positive hepatitis C antibody test result or positive hepatitis C Ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment. Subjects with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained.

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Prashant Kapoor, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Prashant Kapoor, M.D.

Contact us for the latest status

Contact information:

No Contact

Rochester, Minn.

Mayo Clinic principal investigator

Prashant Kapoor, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

International patient clinical studies questions