A Phase I Study to Evaluate the Pharmacokinetics and Safety of GSK2857916 Monotherapy in Participants with Relapsed or Refractory Multiple Myeloma Who Have Normal and Varying Degrees of Impaired Renal Function (DREAMM 12)
|Principal Investigator: Schuster, Michael||Current Status: OPEN TO ACCURAL|
|Phase: I||Protocol Type: Treatment|
|Coordinator: Munoz, Sebastian
|Sponsor Type: Industry
Disease Group: Hematologic Malignancy
Participants are capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the Informed Consent Form.
Male and/or female participants must be 18 years of age or older, at the time of signing the informed consent.
Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
Participants with histologically or cytologically confirmed diagnosis of MM, as defined in International Myeloma Working Group criteria:
Participants has measurable disease with at least one of the following: Serum M-protein >=0.5 grams per deciliter (g/dL) (>=5 grams per liter [g/L]); Urine M-protein >=200 milligrams (mg) per 24 hours (mg/24 h); and Serum free light chain (FLC) assay: Involved FLC level >=10 milligrams per deciliter (mg/dL) (>=100 milligrams per liter [mg/L]) and an abnormal serum FLC ratio (<0.26 or >1.65).
Participants with a history of autologous SCT are eligible for study participation provided the following eligibility criteria are met:
Participants with adequate organ system functions as defined follows:
Absolute neutrophil count >=1.0 x 10^9 per liter (/L); Hemoglobin >=7.0 g/dL or 4.9 millimoles per liter (mmol/L); Platelets >= 50 x 10^9/L; Total bilirubin <=1.5 x Upper limit of normal (ULN) (Isolated bilirubin >=1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent [%]); Alanine aminotransferase <=2.5 x ULN; eGFR,
Group 1: normal/ mild impairment >=60milliliter per minute per 1.73 meter square (mL/min/1.73m^2); Group 2: severe 15-29 mL/min/1.73 m^2; Group 3: ESRD (not on dialysis) <15 mL/min/1.73 m^2; Group 4: ESRD (on dialysis) <15 mL/min/1.73 m^2; and left ventricular ejection fraction by echocardiograms >=40%.
Main additional inclusion criteria in Group 1 (matched control participants): Matched to at least one severely renal impaired participant by Baseline body weight (+/-20%) and Baseline albumin levels (+/-10%).
Female participants: Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is 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 4 months 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 within 72 hours of dosing on Cycle 1 Day 1 and agree to use highly effective contraception during the study and for 4 months after the last dose of study medication. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
Male participants: Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male participants are eligible to participate if they agree to the following from the time of first dose of study until 6 months after the last dose of study treatment to allow for clearance of any altered sperm: Refrain from donating sperm and either; Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; OR must agree to use a male condom even if they have undergone a successful vasectomy and female partner to use an additional highly effective contraceptive method with a failure rate of <1% per year as when having sexual intercourse with a WOCBP (including pregnant females).