None listed
Conditions
Brief summary
The study aims to determine the efficacy of combination therapy with Carfilzomib and Dexamethasone and Belantamab mafodotin (BelaMaf-Kd) for patients with relapsed refractory multiple myeloma. Belantamab mafodotin is a new drug which has not been approved for use by the Therapeutic Goods Administration and so this combination is considered an experimental treatment. Who is it for? You may be eligible to participate in this trial if you are aged 18 years or over, and have received between 1 to 3 prior lines of therapy for multiple myeloma but have not undergone allogeneic stem cell transplantation. Study Details Eligible participants will receive 6 cycles of combination BelaMafKd with treatment given over a 28 day cycle as tolerated. Belantamab mafodotin and Carfilzomib will be delivered by IV infusion on days 1 and 8 and days 1, 8 and 15 respectively. Dexamethasone will be given orally weekly. Participants will be required to have blood samples taken and medical reviews (including ophthalmic examination) at the beginning of each cycle. An ultrasound test of cardiac function will be performed at screening and within 2 weeks of completion of cycle 6. A bone marrow biopsy will be performed at screening, at cycle 6 and to confirm a complete response or disease progression. These assessments will enable researchers to monitor whether the treatment is safe and whether it is effectively treating the myeloma. Study treatments will be halted if participants show disease progression, unacceptable toxicity, or upon withdrawal of consent. A final medical assessment and ophthalmic exam will be performed at end of treatment, with follow up to continue every 12 weeks until one year after the final cycle of treatment. Follow up assessments will continue every 12 weeks until one year after the final cycle of treatment. It is hoped that the findings of this trial will establish the benefits of Belantamab mafodotin in combination with Carfilzomib and Dexamethasone for the treatment of patients with early relapsed multiple myeloma.
Interventions
This is a phase I/II open label single arm clinical study. Patients with relapsed refractory multiple myeloma who have had 1 to 3 prior lines of treatment, will receive Belantamab Mafodotin in combination with carfilzomib and dexamethasone ("BelaMaf-Kd") over alternating treatment cycles of 28 days as follows:
Belantamab mafodotin will be given intravenously over 30 minutes to 1 hour at 2.5mg/kg on day 1 of cycle 1, then on day 1 of every second cycle, i.e. 8 weekly. It will be administered firs
This is a phase I/II open label single arm clinical study. Patients with relapsed refractory multiple myeloma who have had 1 to 3 prior lines of treatment, will receive Belantamab Mafodotin in combination with carfilzomib and dexamethasone ("BelaMaf-Kd") over alternating treatment cycles of 28 days as follows: Belantamab mafodotin will be given intravenously over 30 minutes to 1 hour at 2.5mg/kg on day 1 of cycle 1, then on day 1 of every second cycle, i.e. 8 weekly. It will be administered first (ahead of Carfilzomib) followed by a 1 hour rest period. Carfilzomib will be infused in a 50 -100ml intravenous bag over 30 minutes on day 1, cycle 1 at 20mg/m2, then at 70mg/m2 on days 1, 8 and 15 each cycle onwards. The administration of carfilzomib is as per institutional guideline. Carfilzomib will be administered after Belantamab Mafodotin provided the patient is clinically stable. Dexamethasone 40mg (20mg for patients aged > 75) will be given orally weekly, on days 1, 8, 15 and 22. There will be two phases in the study. The first, safety, run-in phase will consist of 10 patients. After the 10th evaluable patient has completed the 1st cycle, all toxicities that occur will be summarised by worst grade and association with the study treatment. The trial management committee (TMC) will hold a meeting to assess whether or not there are any safety concerns at that dosing schedule. Provided that no more than 3 patients experience a grade 4, treatment-emergent toxicity, and subject to the confirmatory advice from the Data and Safety Monitoring Committee (DSMC), the expansion phase will commence at the same treatment dose and schedule. If 4 or more patients experience grade 4 toxicities, accrual will be paused and the safety ‘run in’ phase repeated at a dose reduction, with the same guidelines for expansion applied. In the expansion phase, alternating BelaMaf-Kd and Kd treatment will continue as long as tolerated, or until patient withdraws consent or disease progresses. Dose level reductions and delays in delivery apply for each therapy based on grade of symptoms and toxicities, and upon medical review. If any of the treatments are stopped as intolerable, the other treatments may continue. Participants will be assessed within 7 days prior to starting each cycle for adverse events, according to CTCAE-NCI v5.0 and by physical examination, including weight and ECOG performance status, blood analysis, including myeloma markers and liver function, urinalysis, and evaluation of myeloma response according to the International Myeloma Working Group definition criteria. Bone marrow biopsy will be performed at screening and within 2 weeks of completion of cycle 6, and to evaluate complete response or disease progression Ocular examination will be performed at screening and day one of each cycle, at end of treatment and for > grade 2 symptoms) Transthoracic Cardiac Echocardiogram will be performed to assess left ventricular ejection fraction at screening and within 2 weeks of completion of cycle 6, and upon grade 3 dyspnoea or at the investigators discretion during symptoms of cardiac failure.
This is a phase I/II open label single arm clinical study. Patients with relapsed refractory multiple myeloma who have had 1 to 3 prior lines of treatment, will receive Belantamab Mafodotin in combination with carfilzomib and dexamethasone ("BelaMaf-Kd") over alternating treatment cycles of 28 days as follows:
• Belantamab mafodotin is given as an infusion (injection into the vein) over between 30 minutes to 1 hour.
o Cohort 1- once every 8 weeks. That is, on cycle 1 day 1, and then day 1 of ev
This is a phase I/II open label single arm clinical study. Patients with relapsed refractory multiple myeloma who have had 1 to 3 prior lines of treatment, will receive Belantamab Mafodotin in combination with carfilzomib and dexamethasone ("BelaMaf-Kd") over alternating treatment cycles of 28 days as follows: • Belantamab mafodotin is given as an infusion (injection into the vein) over between 30 minutes to 1 hour. o Cohort 1- once every 8 weeks. That is, on cycle 1 day 1, and then day 1 of every second cycle i.e. cycle 3 day 1, cycle 5 day 1. The dosage will be calculated at 2.5 milligram per kilogram (mg/kg) of your body weight. o Cohort 2 - once every 12 weeks. That is, on cycle 1 day 1, cycle 3 day 1 and then day 1 of every third cycle i.e. cycle 6 day 1, cycle 9 day 1. The dosage will be calculated at 1.9 milligram per kilogram (mg/kg) of your body weight. • Carfilzomib is administered as an infusion over 30 minutes on days 1, 8, and 15. The first dose on day 1 of cycle 1 is given at a lower dose. • Dexamethasone is a medication given by mouth (40mg) once a week on days 1, 8, 15 and 22 of the 28 day cycle. Recruitment for cohort 1 was completed in August 2023 and cohort 2 is currently open for recruitment.
Sponsors
Australasian Myeloma Research Consortium
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants must have: 1. Male or female, 18 years or older, capable of giving consent. 2. Have confirmed MM as defined by IMWG criteria. 3. ECOG Performance Status 0-2. 4. Have had at least 1 and no more than 3 prior lines of therapy. 5. Must have measurable disease defined as at least one of: o Serum M-protein concentration of greater than or equal to 5g/L o Urine M-protein excretion greater than or equal to 200mg/24hr or o Serum free light chain (FLC) assay: involved FLC level greater than or equal to 100mg/L and an abnormal serum free light chain ration (less than 0.26 or greater than 1.65) 6. Adequate organ system function: o Haematological (transfusion and/or growth factor support within 2 weeks are not permitted for the purpose of meeting eligibility criteria): - Absolute neutrophil greater than or equal to 1.0x10^9/L - Haemoglobin greater than or equal to 80g/L - Platelet greater than or equal to 50x10^9/L o Hepatic: - ALT less than 2.5xULN - Bilirubin unless than 1.5xULN (Isolated bilirubin greater than or equal to 1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%) o Renal: - eGFR greater than 30ml/min - Spot urine (albumin/creatinine ratios) less than 500 mg/g (56 mg/mmol) o Cardiac: - LVEF greater than 45% 7. Female participants: contraceptive use 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 less than 1% per year), preferably with low user dependency (as described in Appendix 6), 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 (as required by local regulations) within 72 hours before the first dose of study intervention. 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 a nearly undetected pregnancy. Non-childbearing potential is defined as follows (by other than medical reasons): - greater than or equal to 45 years of age and has not had menses for greater than 1 year. - Patients who have been amenorrhoeic for less than 2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation. ? - Post-hysterectomy, post-bilateral oophorectomy, or post-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. 8. 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 for 6 months after the last dose of study treatment 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 less than 1% per year as when having sexual intercourse with a woman of childbearing potential (including pregnant females). 9. All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0) must be equal to Grade 1 at the time of enrolment except for alopecia. 10. Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent.
Exclusion criteria
Participants must not have had/be: 1. Systemic anti-myeloma therapy within ?14 days with the exception of corticosteroids equivalent to dexamethasone ?160mg in total within last 4 weeks. 2. Prior treatment with mAb (except for mAb for COVID-19 prophylaxis or management) within 30 days of receiving first dose of study drugs 3. Evidence of cardiovascular risk: - Evidence of current clinically significant untreated arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Mobitz Type II) or 3rd degree atrioventricular (AV) block; Clinically significant, uncontrolled arrhythmias - History of myocardial infarction, acute coronary syndrome (including unstable angina), coronary angioplasty, or stenting or bypass grafting within last 6 months; - Class III or IV heart failure defined by New York Heart Association functional classification system. - Uncontrolled hypertension 4. Pregnant or lactating females. 5. Active infection requiring treatment. 6. Known HIV infection. 7. Active Hepatitis B infection. Patients with positive HBcAB and negative HBsAg are eligible provided HBV DNA is negative. 8. Positive hepatitis C antibody and positive hepatitis C RNA at screening or within 3 months prior to first dose of study treatment. (NOTE: participants with positive hepatitis C antibody due to prior resolved disease can be enrolled only if confirmatory negative hepatitis C RNA is obtained.). 9. Current corneal epithelial disease except for mild changes in corneal epithelium 10. Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to belantamab mafodotin.. 11. Ongoing grade 2 or higher peripheral neuropathy. 12. Known immediate or delayed hypersensitivity reaction to proteasome inhibitors, or unacceptable adverse effects from previous proteasome inhibitors. 13. Participant must not have current unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices, persistent jaundice, or cirrhosis. Note: Stable non-cirrhotic chronic liver disease (including Gilbert’s syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if otherwise meets entry criteria. 14. Participant must not have presence of active renal condition (infection, requirement for dialysis or any other condition that could affect participant’s safety). Participants with isolated proteinuria resulting from MM are eligible, provided they fulfil inclusion criteria. 15. Participant must not use contact lenses while participating in this study. 16. Participant must not be simultaneously enrolled in any interventional clinical trial. 17. Participant must not have used an investigational drug or approved systemic anti-myeloma therapy (including systemic steroids) within 14 days or five half-lives, whichever is shorter, preceding the first dose of study drug. 18. Participant must not have had plasmapheresis within 7 days prior to first dose of study treatment. 19. Participant must not have had major surgery = 4 weeks prior to initiating study treatment. 20. Participant must not have any evidence of active mucosal or internal bleeding. 21. Participant must not have invasive malignancies other than disease under study, unless the second malignancy has been medically stable for at least 2 years and, in the opinion of the principal investigators, will not affect the evaluation of the effects of clinical trial treatments on the currently targeted malignancy. Participants with curatively treated non-melanoma skin cancer may be enrolled without a 2-year restriction. 22. Participant must not have 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.
Outcome results
None listed