Ignite Creation Date:
2024-05-11 @ 8:31 AM
Last Modification Date:
2024-10-26 @ 3:29 PM
Study NCT ID:
NCT06409936
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-18
First Post:
2024-05-07
Brief Title:
PEARL Study PotEntial of Asciminib in the eaRly Treatment of CML
Sponsor:
Gruppo Italiano Malattie EMatologiche dellAdulto
Organization:
Gruppo Italiano Malattie EMatologiche dellAdulto
Study Overview
Official Title:
Asciminib as Single Agent or in Combination With Nilotinib in the 1st-line Treatment of BCR-ABL1 Chronic Myeloid Leukemia a Randomized GIMEMA-GELMC Phase II Study PEARL Study PotEntial of Asciminib in the eaRly Treatment of CML
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-06
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:
PEARL
Brief Summary:
A phase 2 interventional randomized unblinded study will be conducted in newly diagnosed CP CML patients to investigate the efficacy and the safety of asciminib at a dose of 80 mg QD as single agent arm A or 40 mg BID in combination with nilotinib 300 mg BID arm B
All patients in both arm A and arm B will be treated for a minimum of 2 years core phase If they will have achieved a DMR MR4 or if it will be in the interest of the patient the treatment will be continued
During the consolidation phase 2 years asciminib will be continued at the same dose in both arms in the combination arm the nilotinib dose will be reduced to 300 mg daily
The patients maintaining a stable MR4 up to the end of the fourth year will discontinue the treatment TFR phase The rate of TFR at 5 year 1 year after discontinuation will be evaluated
All patients in both arm A and arm B will be treated for a minimum of 2 years core phase If they will have achieved a DMR MR4 or if it will be in the interest of the patient the treatment will be continued
During the consolidation phase 2 years asciminib will be continued at the same dose in both arms in the combination arm the nilotinib dose will be reduced to 300 mg daily
The patients maintaining a stable MR4 up to the end of the fourth year will discontinue the treatment TFR phase The rate of TFR at 5 year 1 year after discontinuation will be evaluated
Detailed Description:
A phase 2 prospective interventional randomized two arms randomization 11 unblinded study will be conducted in newly diagnosed CP CML patients to investigate the efficacy and the safety of asciminib at a dose of 80 mg QD as single agent arm A or 40 mg BID in combination with nilotinib 300 mg BID arm B
In the arm A asciminib 80 mg QD will be given as single-agent In the arm B asciminib 80 mg QD will be started then after 90 days asciminib will be given 40 mg BID and nilotinib 300 mg BID or 300 mg OAD according to the presenceabsence of asciminib adverse events will be added-on in all patients All patients in both arm A and arm B will be treated for a minimum of 2 years core phase If they will have achieved a DMR MR4 or if it will be in the interest of the patient the treatment will be continued In both arms the study drugs may be discontinued at any time for inefficacy failure or safety reasonsgrade 3-4 toxicity or persistent grade 2 non hematologic toxicity However all the patient will remain in study regular follow-up information will be required The dose adjustments for toxicity and detailed criteria for treatment discontinuation asciminib in arm A asciminib or nilotinib in arm B are specified within the protocol
After the induction of a DMR the residual disease will be closely monitored by Q-PCR until the fourth year consolidation phase During the consolidation phase 2 years asciminib will be continued at the same dose in both arms in the combination arm the nilotinib dose will be reduced to 300 mg daily
The patients maintaining a stable MR4 up to the end of the fourth year that must include in the last year at least 3 evaluable QPCR analyses will enter the treatment free remission TFR phase of the study and will discontinue the treatment TFR phase A single unconfirmed loss of MR4 will not preclude the possibility of treatment discontinuation In case of confirmed loss of MR3 after discontinuation the choice of subsequent treatment will be up to Local Investigators The rate of TFR at 5 year 1 year after discontinuation will be evaluated
In the arm A asciminib 80 mg QD will be given as single-agent In the arm B asciminib 80 mg QD will be started then after 90 days asciminib will be given 40 mg BID and nilotinib 300 mg BID or 300 mg OAD according to the presenceabsence of asciminib adverse events will be added-on in all patients All patients in both arm A and arm B will be treated for a minimum of 2 years core phase If they will have achieved a DMR MR4 or if it will be in the interest of the patient the treatment will be continued In both arms the study drugs may be discontinued at any time for inefficacy failure or safety reasonsgrade 3-4 toxicity or persistent grade 2 non hematologic toxicity However all the patient will remain in study regular follow-up information will be required The dose adjustments for toxicity and detailed criteria for treatment discontinuation asciminib in arm A asciminib or nilotinib in arm B are specified within the protocol
After the induction of a DMR the residual disease will be closely monitored by Q-PCR until the fourth year consolidation phase During the consolidation phase 2 years asciminib will be continued at the same dose in both arms in the combination arm the nilotinib dose will be reduced to 300 mg daily
The patients maintaining a stable MR4 up to the end of the fourth year that must include in the last year at least 3 evaluable QPCR analyses will enter the treatment free remission TFR phase of the study and will discontinue the treatment TFR phase A single unconfirmed loss of MR4 will not preclude the possibility of treatment discontinuation In case of confirmed loss of MR3 after discontinuation the choice of subsequent treatment will be up to Local Investigators The rate of TFR at 5 year 1 year after discontinuation will be evaluated
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