DREAMM 13: A Study of Belantamab Mafodotin in Multiple Myeloma Participants With Normal and Impaired Hepatic Function

Sponsor
GlaxoSmithKline (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04398680
Collaborator
(none)
28
22
3
44.7
1.3
0

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the pharmacokinetics (PK), safety, and tolerability of belantamab mafodotin monotherapy in Relapsed/Refractory Multiple Myeloma (RRMM) participants with impaired hepatic function and in matched RRMM participants with normal hepatic function.

Condition or Disease Intervention/Treatment Phase
  • Drug: Belantamab mafodotin
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
28 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Masking Description:
This is an open-label study.
Primary Purpose:
Treatment
Official Title:
A Phase I Study to Evaluate the Pharmacokinetics and Safety of Belantamab Mafodotin Monotherapy in Participants With Relapsed or Refractory Multiple Myeloma Who Have Normal and Varying Degrees of Impaired Hepatic Function (DREAMM 13)
Actual Study Start Date :
Apr 20, 2021
Anticipated Primary Completion Date :
Dec 10, 2024
Anticipated Study Completion Date :
Jan 10, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part 1, Group 1: Participants with normal hepatic function

Participants with normal hepatic function (Serum bilirubin and Aspartate aminotransferase [AST] less than or equal to [<=] Upper limit of normal [ULN]) will be administered with Belantamab mafodotin

Drug: Belantamab mafodotin
Belantamab mafodotin will be administered

Experimental: Part 1, Group 2: Participants with moderate hepatic impairment

Participants with moderate hepatic impairment (Serum bilirubin greater than >1.5 - 3 times ULN and any AST) will be administered with Belantamab mafodotin

Drug: Belantamab mafodotin
Belantamab mafodotin will be administered

Experimental: Part 2,Group 3: Participants with severe hepatic impairment

Participants with severe hepatic impairment (Serum bilirubin >3 times ULN and any AST) will be administered with Belantamab mafodotin

Drug: Belantamab mafodotin
Belantamab mafodotin will be administered

Outcome Measures

Primary Outcome Measures

  1. Part 1 and Part 2: Maximum observed plasma concentration (Cmax) of GSK2857916 [Up to 48 months]

  2. Part 1 and Part 2: Time to Cmax (Tmax) of GSK2857916 [Up to 48 months]

  3. Part 1 and Part 2: Concentration at the end of infusion (C-EOI) [Up to 48 months]

  4. Part 1 and Part 2: Predose plasma concentration (Ctrough) of GSK2857916 [Up to 48 months]

  5. Part 1 and Part 2: Area under the plasma concentration-time curve (from zero to the end of dosing interval) [Up to 48 months]

  6. Part 1 and Part 2 : AUC over the dosing interval (AUC[0-tau]) of GSK2857916 [Up to 48 months]

  7. Part 1 and Part 2: Last time point where the concentration is above the limit of quantification (Tlast) of GSK2857916 [Up to 48 months]

  8. Part 1 and Part 2: Cmax of total monoclonal antibody (mAb) [Up to 48 months]

  9. Part 1 and Part 2: Tmax of total mAb [Up to 48 months]

  10. Part 1 and Part 2: C-EOI of total mAB [Up to 48 months]

  11. Part 1 and Part 2: Ctrough of total mAb [Up to 48 months]

  12. Part 1 and Part 2: Area under the plasma concentration-time curve (from zero to the end of dosing interval)of total mAb [Up to 48 months]

  13. Part 1 and Part 2: AUC(0-tau) of total mAb [Up to 48 months]

  14. Part 1 and Part 2: Tlast of total mAb [Up to 48 months]

  15. Part 1 and Part 2: Cmax of Cys Monomethyl Auristatin F (cys-mcMMAF) [Up to 48 months]

  16. Part 1 and Part 2: Tmax of cys-mcMMAF [Up to 48 months]

  17. Part 1 and Part 2: C-EOI of cys-mcMMAF [Up to 48 months]

  18. Part 1 and Part 2: AUC(0-168 hours) of cys-mcMMAF [Up to 48 months]

  19. Part 1 and Part 2: tlast of cys-mcMMAF [Up to 48 months]

Secondary Outcome Measures

  1. Part 1 and Part 2: Change from Baseline in Vital Signs- Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) (millimeters of mercury [mmHg]) [Baseline and up to 4 years]

  2. Part 1 and Part 2: Change from Baseline in Vital Sign- Heart rate (beats per minute) [Baseline and up to 4 years]

  3. Part 1 and Part 2: Number of participants with adverse events (AEs) and serious adverse events (SAEs) [Up to 4 years]

  4. Part 1 and Part 2: Number of participants with toxicity grading for hematology parameters [Up to 4 years]

  5. Part 1 and Part 2: Number of participants with toxicity grading for clinical chemistry parameters [Up to 4 years]

  6. Part 1 and Part 2: Number of participants with toxicity grading for urine parameters [Up to 4 years]

  7. Part 1 and Part 2: Number of participants with abnormal physical examination parameters [Up to 4 years]

    Physical examination parameters will include assessments of the head, eyes, ears, nose, throat, skin, thyroid, lungs, cardiovascular, abdomen (liver and spleen), lymph nodes, and extremities.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • 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 must be 18 years of age or older, at the time of signing the informed consent.

  • Eastern Cooperative Oncology Group performance status 0-2.

  • Participants with histologically or cytologically confirmed diagnosis of multiple myeloma, as defined in International Myeloma Working Group criteria: 1. Has undergone autologous stem cell transplant (SCT) or is considered transplant-ineligible; 2. Has failed at least 2 prior lines of anti-myeloma treatments, including an immunomodulatory drugs (example [e.g.], lenalidomide or pomalidomide) and a proteasome inhibitor (e.g., bortezomib, ixazomib or carfilzomib).

  • Participants has measurable disease with at least one of the following: Serum M-protein greater than or equal to (>=)0.5 grams per deciliter (g/dL) >=5 grams per liter [g/L]); Urine M-protein >=200 milligram per 24 hours (mg/24 hr); and Serum free light chain assay: Involved free light chain level >=10 milligrams per deciliter (mg/dL) (>=100 milligrams per liter [mg/L]) and an abnormal serum free light chain 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: 1. Transplant was >100 days prior to study enrollment, 2. No active infection(s), and 3. Participant meets the remainder of the eligibility criteria outlined in this protocol.

  • Participants with adequate organ system functions as defined follows: Absolute neutrophil count >=1.0 times 109/liter (L); Hemoglobin >=8.0 g/dL (or 4.9 millimoles per liter); Platelets >= 75 times 109/L; Serum bilirubin and aspartate aminotransferase: Group 1 (normal) serum bilirubin and aspartate aminotransferase <=upper limit of normal (ULN); Group 2 (moderate) serum bilirubin >1.5-3 times ULN and any aspartate aminotransferase; alanine aminotransferase <=5 ULN; Estimated glomerular filtration rate >=60 milliliter per minute per 1.73 meter square (mL/min/m^2); Urine dipstick for protein or Albumin/creatinine ratio (from spot urine) negative/trace (if

=1+ only eligible if confirmed <=500 mg/g (56 mg/mmol) by albumin/creatinine ratio (spot urine from first void; and left ventricular ejection fraction by echocardiograms =45 percent (%).

  • Main additional inclusion criteria in Group 1 (matched control participants): Matched to at least one moderate hepatic impaired participant by Baseline albumin levels (+/-10%) and Baseline weight (+/-20%).

  • 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 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).

  • 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.

  • Participants with a history of Hepatitis B virus and/or Hepatitis C virus exposure are eligible under specific conditions.

Exclusion Criteria:
  • Active plasma cell leukemia at the time of screening. Symptomatic amyloidosis, active polyneuropathy, organomegaly, endocrinopathy, myeloma protein and skin changes, Waldenstroem Macroglobulinemia.

  • Participants had a prior allogeneic SCT.

  • Prior belantamab mafodotin therapy

  • Systemic active infection requiring treatment

  • Any unresolved toxicity >=Grade 2 from previous treatment except for alopecia, or peripheral neuropathy up to Grade 2.

  • Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including lab abnormalities except hepatic impairment) 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 sudden onset of, or clinically relevant changes in: ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, in the last 14 days prior to the first dose. Participants with cirrhosis are excluded. Participants with focal lesions due to other causes than underlying multiple myeloma are excluded.

  • Participants with acute hepatitis B virus infection are excluded. Participants with chronic hepatitis B infection (active or core antibody positive) are only allowed if the criteria from Organ System Function are fulfilled and if appropriate antiviral treatment per local guidance (e.g. tenofovir or entecavir) is started before starting belantamab mafodotin, continues through to completion of belantamab mafodotin therapy and is not to be stopped unless advised by local hepatology or virology.

  • Participants with evidence of hepatitis C virus infection, defined as positive hepatitis C virus - ribonucleic acid test result at screening or within 3 months prior to first dose of study treatment, are excluded unless successfully treated prior to enrollment with a curative 8-12 week antiviral treatment course and the hepatitis C virus - ribonucleic acid negative status has been confirmed after at least 4 weeks washout of the antiviral treatment.

  • Participants with Gilbert's syndrome.

  • Evidence of cardiovascular risk including any of the following: Evidence of current clinically significant untreated arrhythmias, including clinically significant electrocardiogram abnormalities including second degree (Mobitz Type II) or third degree atrioventricular block; History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of Screening; Class III or IV heart failure as defined by the New York Heart Association functional classification system; History of severe non-ischemic cardiomyopathy; and Uncontrolled hypertension.

  • Known human immunodeficiency virus infection.

  • Current corneal epithelial disease except for mild punctuate keratopathy.

  • Participant is a woman who is pregnant or breastfeeding.

Contacts and Locations

Locations

Site City State Country Postal Code
1 GSK Investigational Site Tucson Arizona United States 85724
2 GSK Investigational Site Beverly Hills California United States 90211
3 GSK Investigational Site Plantation Florida United States 33322
4 GSK Investigational Site Chicago Illinois United States 60611
5 GSK Investigational Site Wichita Kansas United States 67214
6 GSK Investigational Site Baltimore Maryland United States 21201-1595
7 GSK Investigational Site Hackensack New Jersey United States 07601
8 GSK Investigational Site Monroeville Pennsylvania United States 15146
9 GSK Investigational Site The Woodlands Texas United States 77380
10 GSK Investigational Site Milwaukee Wisconsin United States 53233
11 GSK Investigational Site Athens Greece 10676
12 GSK Investigational Site Athens Greece 11528
13 GSK Investigational Site Busan Korea, Republic of 49201
14 GSK Investigational Site Busan Korea, Republic of 49241
15 GSK Investigational Site Daegu Korea, Republic of 41944
16 GSK Investigational Site Hwasun Korea, Republic of 58128
17 GSK Investigational Site Incheon Korea, Republic of 405-760
18 GSK Investigational Site Jeonju-si Korea, Republic of 561-172
19 GSK Investigational Site Seoul Korea, Republic of 03080
20 GSK Investigational Site Seoul Korea, Republic of 06591
21 GSK Investigational Site Seoul Korea, Republic of 120-752
22 GSK Investigational Site Suwon-si, Gyeonggi-do Korea, Republic of 16499

Sponsors and Collaborators

  • GlaxoSmithKline

Investigators

  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT04398680
Other Study ID Numbers:
  • 209627
First Posted:
May 21, 2020
Last Update Posted:
Jul 21, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by GlaxoSmithKline
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 21, 2022