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Clinical Trial Summary

This is a phase I-II open-label, multicenter, non-randomized study aiming to evaluate the efficacy and safety of belantamab mafodotin in combination with carfilzomib (Kyprolis®) and dexamethasone (Kd). Since this is the first time that this combination is being evaluated in a clinical trial, a first dose escalation part will be developed following the classic 3+3 design, to establish the maximum tolerated dose (MTD) of the combination. Once the MTD will be defined, a dose expansion phase will be open to recruit up to 60 patients. Patients will receive treatment with belantamab-mafodotin + Kd, until unacceptable toxicity, disease progression, patient withdrawal, loss to follow-up, end of study, or death.


Clinical Trial Description

This is a phase I-II open-label, multicenter, non-randomized study aiming to evaluate the efficacy and safety of belantamab mafodotin in combination with carfilzomib (Kyprolis®) and dexamethasone (Kd). Since this is the first time that this combination is being evaluated in a clinical trial, a first dose escalation part will be developed following the classic 3+3 design, to establish the maximum tolerated dose (MTD) of the combination. Once the MTD will be defined, a dose expansion phase will be open to recruit up to 60 patients. The study comprises the following phases: Phase 1 (Lead-in): 3+3 Dose escalation In the phase 1 of the study, aiming to establish the recommended phase 2 dose (RP2D), patients will be included following the classic 3 + 3 design. Dose levels will be as follows: Dose level -1 - Belantamab-Mafodotin 1.9 mg/kg day 1, Q8W - Carfilzomib 20/45 mg/m2 on days 1, 8, and 15, Q4W. - Dexamethasone 40 mg weekly (days 1, 8, 15 and 22) or 20 mg in patients > 75 years old, Q4W Dose level 1 - Belantamab-Mafodotin 2.5 mg/kg day 1, Q8W - Carfilzomib 20/45 mg/m2 days 1, 8, and 15, Q4W. - Dexamethasone 40 mg weekly (days 1, 8, 15 and 22) or 20 mg in patients > 75 years old., Q4W Dose level 2 - Belantamab-Mafodotin 2.5 mg/kg on day 1, Q8W - Carfilzomib 20/56 mg/m2 on days 1, 8, and 15, Q4W. - Dexamethasone 40 mg weekly (days 1, 8, 15 and 22) or 20 mg in patients > 75 years old, Q4W. Dose level 3 - Belantamab-Mafodotin 2.5 mg/kg on day 1, every 4 weeks (Q8W) - Carfilzomib 20/70 mg/m2 on days 1, 8, and 15, Q4W. - Dexamethasone 40 mg weekly (days 1, 8, 15 and 22) or 20 mg in patients > 75 years old., Q4W The rules applied for the Lead-in phase are as follows: 1. An initial cohort of 3 subjects is enrolled at the first dose level (DL1). 2. If 1/3 subjects develop a DLT, 3 additional patients will be included at the same dose level (DL1) 3. If 0/3 subjects develop a DLT, 3 additional patients will be included at the next dose level (DL2, dose level 2). 4. If 1/3 subjects develop a DLT, 3 additional patients will be included at the same dose level (DL2, dose level 2). 5. If 0 of the 3 new subjects develops a DLT (for a total of 0-1/6 patients with a DLT at this dose level), 3 new subjects will be included in DL3 (dose level 3). 6. If 1 of the 3 new subjects develops a DLT (for a total of 0-1/6 patients with a DLT at this dose level), 3 new subjects will be included at the same dose level (DL3, dose level 3) 7. If 0 out of the 3 new subjects develops a DLT, 3 additional subjects will be included in the same dose level. If 0-1 out of 6 patients developed a DLT, this dose will be considered the maximum tolerated dose (MTD) and will be explored in the expansion phase (phase 2). 8. If ≥2/3 subjects develop a DLT, dose level will be de-escalated (previous dose level) with the same rules as described above. Dose limiting toxicities (DLTs) will be evaluated during the DLT evaluation period. The DLT evaluation period will be defined as the first 4-weeks treatment cycle for each cohort. Patients participating in the Lead-In-Phase must undergo a complete ophthalmologic examination at the end of the DLT evaluation period (4-weeks) and before starting Cycle 2. Subjects will be considered evaluable for the assessment of DLT if they: - Received at least 1 dose of belantamab mafodotin + Kd and experience a DLT, OR - Received at least 1 dose of belantamab mafodotin, 3 doses of Carfilzomib and 3 doses of Dexamethasone and complete the safety follow-up through the end of the DLT evaluation period. Non-evaluable subjects will be replaced. Phase 2 (Expansion Phase, n= up to 60 patients) Combination treatment will be administered at the RP2D based on the results of the phase 1 dose escalation part of the study: - Belantamab mafodotin on day 1 at the RP2D, every 8 weeks, intravenously (IV). - Carfilzomib will be given at the RP2D weekly IV on days: 1, 8, and 15 of every 4-week cycle (Q4W). - Dexamethasone will be given at the dose of 40 mg (or 20 mg if patient > 75 years old) on days: 1, 8, 15 and 22 Q4W. From month 13 onwards carfilzomib treatment will be given on day 1 and 15 of every 4-weeks cycles. Belantamab will be given at the RP2D every 8 weeks and Dexamethasone 40mg on days 1, 8, and 15 of every 4-week cycle. The trial has the following objectives: Primary objectives (PO): Phase 1 PO1: To determine the maximum tolerated dose, and the recommended phase 2 dose of belantamab mafodotin in combination with carfilzomib and dexamethasone. Phase 2 PO2: To evaluate the efficacy in terms of complete response rate and rates of minimal residual negativity after 12 months of therapy with belantamab mafodotin combined with carfilzomib and dexamethasone. PO3: To evaluate safety and tolerability of the combination of belantamab mafodotin plus carfilzomib and dexamethasone. Secondary Objectives (SO): SO1: To determine time to event data of the combinations: Progression-free survival, progression-free survival at 12 months, duration of response, time to response, and overall survival. SO2: Evaluate deepening of response during continuous therapy at 12, and 24 months. SO3: Evaluate sustained MRD rate at 1 and 2 years. SO4: Evaluate the rate of conversion from MRD positivity to MRD negativity during the treatment (yearly). SO5: To assess the safety of the combination of belantamab mafodotin + Kd, as well as the incidence of corneal and ophthalmologic adverse events. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT05060627
Study type Interventional
Source PETHEMA Foundation
Contact Carmen López-Carrero
Phone 0034 699 835 437
Email [email protected]
Status Not yet recruiting
Phase Phase 1/Phase 2
Start date September 30, 2021
Completion date May 30, 2028

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