Ignite Creation Date:
2024-05-06 @ 4:42 PM
Last Modification Date:
2024-10-26 @ 2:14 PM
Study NCT ID:
NCT05060627
Status:
RECRUITING
Last Update Posted:
2022-09-08
First Post:
2021-09-17
Brief Title:
Study of Belantamab Mafodotin in Combination With Kd for the Treatment of Relapsed Myeloma Patients Refractory to Lenalidomide
Sponsor:
PETHEMA Foundation
Organization:
PETHEMA Foundation
Study Overview
Official Title:
An Open Label Multicenter Phase III Study of Belantamab Mafodotin in Combination With Kd for the Treatment of Relapsed Myeloma Patients Refractory to Lenalidomide
Status:
RECRUITING
Status Verified Date:
2022-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 33 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
Patients will receive treatment with belantamab-mafodotin Kd until unacceptable toxicity disease progression patient withdrawal loss to follow-up end of study or death
Detailed 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 33 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 33 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 19 mgkg day 1 Q8W
Carfilzomib 2045 mgm2 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 25 mgkg day 1 Q8W
Carfilzomib 2045 mgm2 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 25 mgkg on day 1 Q8W
Carfilzomib 2056 mgm2 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 25 mgkg on day 1 every 4 weeks Q8W
Carfilzomib 2070 mgm2 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 13 subjects develop a DLT 3 additional patients will be included at the same dose level DL1
3 If 03 subjects develop a DLT 3 additional patients will be included at the next dose level DL2 dose level 2
4 If 13 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 0-16 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 0-16 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 23 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
The study comprises the following phases
Phase 1 Lead-in 33 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 19 mgkg day 1 Q8W
Carfilzomib 2045 mgm2 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 25 mgkg day 1 Q8W
Carfilzomib 2045 mgm2 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 25 mgkg on day 1 Q8W
Carfilzomib 2056 mgm2 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 25 mgkg on day 1 every 4 weeks Q8W
Carfilzomib 2070 mgm2 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 13 subjects develop a DLT 3 additional patients will be included at the same dose level DL1
3 If 03 subjects develop a DLT 3 additional patients will be included at the next dose level DL2 dose level 2
4 If 13 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 0-16 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 0-16 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 23 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2021-002125-15 | EUDRACT_NUMBER | None | None |