Evaluation of Belantamab Mafodotin in Adults with Primary Immune Thrombocytopenia Post-Thrombopoietin Receptor Agonist and/or Rituximab Therapy
- Trial ID
- 2023-509131-12-01
- Protocol
- EAE140
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this phase II trial is to evaluate the **clinical efficacy** of treatment with belantamab mafodotin in adult patients with **Primary Immune Thrombocytopenia** who have previously been treated with a thrombopoietin receptor agonist and/or rituximab following corticosteroid first-line therapy. This objective is clinically relevant as it aims to determine the potential of belantamab mafodotin to improve patient outcomes in a population with limited treatment options.
Secondary objectives include:
- To evaluate the **safety** of treatment with belantamab mafodotin, which is crucial for understanding the risk-benefit profile of the drug.
- To further evaluate the clinical efficacy of treatment with belantamab mafodotin, providing additional insights into its therapeutic potential.
- To evaluate vision-related functioning measured by the Vision Related Anamnestic Tool as documented by the investigator, which is important for assessing the impact of treatment on patients' quality of life.
Participants
The clinical trial focuses on evaluating the efficacy of belantamab mafodotin in participants diagnosed with **Primary Immune Thrombocytopenia**. The sponsor has not provided information regarding the total number of participants. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a platelet cell count of less than 30x10^9/L and must have undergone prior first-line therapy with corticosteroids, as well as second-line therapy with TPO-RA and/or rituximab, without achieving or retaining a response. Adequate organ function is necessary, as defined by specific hematologic, hepatic, and renal parameters. Lifestyle considerations include the use of effective contraception for both male and female participants, in accordance with local regulations, to prevent pregnancy during and after the trial period. The trial includes a vulnerable population, and participants must have an Eastern Cooperative Oncology Group Performance Status of 2 or less. All participants are required to provide written informed consent, demonstrating their understanding of the trial procedures.
Plans and Procedures
The clinical trial is designed to evaluate the **clinical efficacy** and safety of **belantamab mafodotin** in adult patients with **primary immune thrombocytopenia** who have previously been treated with a thrombopoietin receptor agonist and/or rituximab following corticosteroid first-line therapy. This is a Phase II, randomized, double-blind, controlled trial. The trial is expected to commence recruitment on December 16, 2024, and conclude by January 16, 2027. The trial will involve multiple study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific criteria, including age, prior treatments, and organ function. Participants must be 18 years or older, with a platelet count of less than 30x10^9/L, and have adequate organ function as defined by laboratory assessments.
Following the screening, eligible participants will be randomized to receive the investigational product, administered as a **powder for solution for injection** via **intravenous use**. The primary endpoint is the complete response rate/partial response rate at six months of treatment. Secondary endpoints include the overall response rate at 2, 6, and 12 months, time to response, duration of response, and the number of participants with treatment-emergent adverse events. Study visits will be scheduled at regular intervals to monitor the participants' response to treatment and any adverse events. The end-of-study visit will occur after the final treatment cycle, or earlier if the participant meets criteria for early termination, such as withdrawal of consent or significant adverse events.
Participant involvement is expected to last up to 12 months, with the possibility of early termination if the participant experiences unacceptable toxicity, disease progression, or withdraws consent. The trial will adhere to stringent ethical standards, ensuring that all participants provide written informed consent before enrollment. The trial's design and procedures aim to ensure the collection of robust data to assess the investigational product's efficacy and safety in the target population.
Treatment
The clinical trial involves the administration of **belantamab mafodotin**, an experimental medication developed by GlaxoSmithKline. This investigational drug is provided in the form of a **powder for solution for injection**. The active substance, belantamab mafodotin, is a protein-based compound classified under the category "Protein - Other." The pharmaceutical form is specifically designed for **intravenous use**. The dosing regimen for this trial does not specify a maximum daily dose or total dose amount, but the treatment period is capped at 12 months. The administration of belantamab mafodotin is intended to evaluate its clinical efficacy in adult patients with primary immune thrombocytopenia who have previously been treated with a thrombopoietin receptor agonist and/or rituximab following corticosteroid first-line therapy.
In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are mentioned. The focus is solely on the investigational product, belantamab mafodotin. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol. The trial aims to assess the safety and clinical activity of belantamab mafodotin, with the primary objective being the evaluation of its clinical efficacy in the specified patient population.
Efficacy
The clinical trial will assess the efficacy of **belantamab mafodotin** in adult patients with primary immune thrombocytopenia (ITP) who have previously been treated with a thrombopoietin receptor agonist and/or rituximab following corticosteroid first-line therapy. The primary endpoint for evaluating efficacy is the complete response rate (CRR) and partial response rate (PRR) at 6 months of treatment. Secondary endpoints include the overall response rate (ORR) at 2, 6, and 12 months, complete response rate at 12 months, time to response (TTR), duration of response (DoR), and the number and proportion of participants with changes from baseline in ocular symptoms and related impacts as measured by the Vision Related Anamnestic Tool.
Data collection will involve monitoring patients for treatment-emergent adverse events (AEs) and serious AEs, as well as conducting ophthalmic exams to identify abnormal ocular findings. The trial will also track belantamab mafodotin dose holds. Efficacy assessments will be conducted at specified intervals throughout the trial duration, with the primary endpoint evaluated at the 6-month mark. The trial is designed to ensure comprehensive data collection and analysis to determine the clinical efficacy of the treatment regimen.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participants must be 18 years or older.
- Primary ITP with platelet cell count of less than 30x10^9/L.
- Prior first-line therapy with corticosteroids.
- Prior second-line therapy with TPO-RA and/or rituximab and failure to achieve or retain response.
- Adequate organ system function as defined by the below laboratory assessments. Hematologic a. Absolute neutrophil count ≥1.5x10^9/L; granulocyte colony stimulating factor use within the past 14 days is NOT permitted. b. Hemoglobin ≥8.0 g/dL; transfusions within the past 14 days are NOT permitted. Erythropoietin use is allowed. Hepatic a. Total bilirubin ≤1.5xULN (isolated bilirubin ≥1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). b. Alanine aminotransferase ≤ 2.5xULN. Renal a. Estimate glomerular filtration rate ≥30 mL/min/1.73 m2 calculated using the Modification of Diet in Renal Disease formula.
- Female participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical trials: 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) defined as follows: a. ≥45 years of age and has not had menses for >1 year with no other cause. b. Any participant who have been amenorrhoeic for >1year but <2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation. c. Post-hysterectomy, post-bilateral oophorectomy, or post-bilateral tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure. OR • Is a WOCBP 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 4 months after the last dose of belantamab mafodotin 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 trial intervention. • WOCBP must have a negative highly sensitive serum pregnancy test within 10 to 14 days prior to the start of treatment and the second pregnancy test must be performed within 24 hours prior to the start of treatment and agree to use a highly effective method of contraception during the trial and for 4 months after the last dose of belantamab mafodotin. Additional requirements for pregnancy testing during and after trial intervention are provided in Section 10. Trial Procedures and Visit Schedule. The investigator is responsible for a review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with a nearly undetected pregnancy.
- Male participants: contraceptive use 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 during the intervention period and until 6 months after the last dose of belantamab mafodotin, whichever is longer, to allow for clearance of any altered sperm. • Refrain from donating sperm PLUS 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 contraception/barrier as detailed below: 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 woman of childbearing potential (including pregnant females).
- Eastern Cooperative Oncology Group Performance Status ≤2.
- Participants must be able to understand the trial procedures and agree to participate in the trial by providing written informed consent.
Exclusion Criteria
- Secondary ITP including: i. Drug induced ITP. ii. ITP associated with any autoimmune disorders (e.g., systemic lupus erythematosus, and rheumatoid arthritis). iii. ITP associated with chronic infection including but not limited to (e.g., human immunodeficiency virus, hepatitis C virus, and helicobacter pylori). iv. ITP associated with malignancy (e.g., chronic lymphocytic leukemia or large granular T-lymphocyte lymphocytic leukemia).
- Chronic liver disease. Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice. NOTE: Stable non-cirrhotic chronic liver disease (including Gilbert’s syndrome or asymptomatic gallstones) is acceptable if participant otherwise meets entry criteria.
- To be seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]) at screening or within 3 months prior to first dose of trial treatment. NOTE 1: Participants with resolved infection (i.e., participants who are positive for antibodies to hepatitis B core antigen [anti-HBc] or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR). Those who are PCR positive will be excluded. NOTE 2: presence of anti-HBs indicating previous vaccination will not constitute an exclusion criterion.
- To be seropositive for hepatitis C at screening or within 3 months prior to first dose of trial treatment. NOTE: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained. Hepatitis RNA testing is optional and participants with negative hepatitis C antibody test do not require to also undergo hepatitis C RNA testing.
- Known HIV infection, unless the participant meets all of the following criteria: a. Established anti-retroviral therapy (ART) for at least 4 weeks and HIV viral load <400 copies/mL b. CD4+ T-cell (CD4+) counts ≥350 cells/uL c. No history of AIDS-defining opportunistic infections within the last 12 months NOTE: consideration must be given to ART and prophylactic antimicrobials that may have a drug:drug interaction and/or overlapping toxicities with belantamab mafodotin or other combination products as relevant.
- Active infection requiring treatment.
- Active renal condition (infection, requirement for dialysis, or any other significant condition that could affect participant’s safety).
- Any serious and/or unstable pre-existing medical or psychiatric disorder, or other conditions (including laboratory abnormalities) that could interfere with participant’s safety, obtaining informed consent, or compliance to the trial procedures.
- Participant must not have received a live or live-attenuated vaccine within 30 days prior to first dose of belantamab mafodotin.
- Current corneal epithelial disease except for mild punctate keratopathy. NOTE: Participants with mild punctate keratopathy are allowed. Mild (Grade 1) punctuate keratopathy is characterized by the appearance of only a few, if any, microcyst-like epithelial changes, as identified in the slit-lamp examination, with a low density (non-confluent), and predominantly (≥80%) located in the periphery of the cornea.
- Known intolerance or immediate or delayed hypersensitivity reaction or idiosyncratic reaction to: drugs chemically related to belantamab mafodotin, or dexamethasone or any of the components of the trial treatment; or infused protein products, sucrose, histidine, and polysorbate 80.
- Use of an investigational drug within 14 days or 5 halflives (whichever is shorter)preceding the first dose of trial drug.
- Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of trial drug. Please note,monoclonal antibodies for serious conditions unrelated to ITP, such as COVID, may be permitted but need to be discussed with the Sponsor
- Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes) or active plasma cell leukemia at the time of screening
- Evidence of active mucosal or internal bleeding.
- Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain
- Major surgery within 4 weeks before the first dose of trial drug. NOTE 1: participants must be clinically stable following a major surgery to be entered in the trial. NOTE 2: major surgery shall be defined based on the Investigator’s judgment according to the extent and complexity of the procedure, its pathophysiological consequences and consecutive clinical outcomes.
- Evidence of cardiovascular risk including any of the following: i. Evidence of current clinically significant untreated arrhythmias, including clinically significant electrocardiogram (ECG) abnormalities, second degree (Mobitz Type II), or third degree atrioventricular block. ii. Screening 12-lead ECG showing a baseline QT interval >470 msec iii. History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within 3 months of Screening. iv. Class III or IV heart failure as defined by the New York Heart Association functional classification system (Appendix 3 – New York Heart association (NYHA) Classification v. Uncontrolled hypertension
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Greece | Recruiting | 16 Dec 2024 | 14 |