Ignite Creation Date:
2024-10-26 @ 3:37 PM
Last Modification Date:
2024-10-26 @ 3:37 PM
Study NCT ID:
NCT06544785
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-08-05
Brief Title:
Zanubrutinib With Obinutuzumab in Untreated Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Sponsor:
None
Organization:
None
Study Overview
Official Title:
A Multicenter Phase 2 Randomized Open Label Study to Evaluate Zanubrutinib in Combination With Obinutuzumab in Previously Untreated Patients With Chronic Lymphocytic Leukemia CLL or Small Lymphocytic Lymphoma SLL GELLC-10-ZANUBIO
Status:
RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The goal of this phase II randomized open label study is to compare the rate of complete remission CR with undetectable minimal residual disease uMRD obtained with zanubrutinib in combination with obinutuzumab with two different schedules of administration of obinutuzumab starting obinutuzumab at cycle 2 or 12 months in patients with previously untreated Chronic Lymphocytic Leukemia CLL or Small Lymphocytic Lymphoma SLL There is scarce information about which is the most appropriate schedule of combining the BTKi and the anti-CD20 monoclonal antibody and whether treatment can be safely stopped in those patients attaining deep responses CR with uMRD remains to be determined
Response will be assessed after 20 cycles of treatment for the primary objective of the study Patients attaining uMRD will stop treatment with zanubrutinib whereas the rest of patients will continue on treatment with zanubrutinib until progression unacceptable toxicity or trial completion whichever comes first
Response will be assessed after 20 cycles of treatment for the primary objective of the study Patients attaining uMRD will stop treatment with zanubrutinib whereas the rest of patients will continue on treatment with zanubrutinib until progression unacceptable toxicity or trial completion whichever comes first
Detailed Description:
This a multicenter phase 2 randomized open label study of the Spanish Group of CLL GELLC for patients with untreated CLLSLL with 2 arms of treatment In this study 106 patients from 20 centers in Spain with untreated CLLSLL will be randomized 11 to arm A n 53 or arm B n 53 The randomization will be stratified according to the presenceabsence of deletionmutation 17pTP53 at the time of inclusion and based on the randomization list generated by the study statistician
Arm A Patients will be treated with the combination of zanubrutinib 320 mg PO qDay and obinutuzumab starting obinutuzumab at cycle 2 to reduce infusion-related reactions Intravenous obinutuzumab will be given on days 1 100 mg 2 900 mg 8 1000 mg and 15 1000 mg of cycle 2 and on day 1 1000 mg of cycles 3-7
Arm B Patients will start treatment with zanubrutinib 320 mg PO qDay in monotherapy After 12 cycles of zanubrutinib patients will be treated with the combination of zanubrutinib and obitnutuzumab Intravenous obinutuzumab will be given on days 1 100 mg 2 900 mg 8 1000 mg and 15 1000 mg of cycle 13 and on day 1 1000 mg of cycles 14-18
Response will be assessed after 20 cycles of treatment for the primary objective of the study Patients that in the evaluation of cycle 20 who achieve uMRD 001 tumour cells by flow cytometry will stop treatment with zanubrutinib whereas the rest of patients will continue on treatment with zanubrutinib until progression unacceptable toxicity or trial completion whichever comes first Patients who achieve an uMRD in bone marrow beyond C20 will also be allowed to stop the treatment whereas the rest of patients will continue on treatment with zanubrutinib until progression unacceptable toxicity or trial completion whichever comes first
In addition the efficacy and safety of the combination therapy with two different administration schedules of obinutuzumab will be analysed through the following outcome measures i Overall response rate including Complete Remission CR CR with incomplete marrow recovery CRi Partial Remission PR and partial response with lymphocytosis ii MRD analysis iiI Duration of response and progression-free survival PFS iv Safety type frequency and severity of adverse events AEs and relationship of AEs to zanubrutinib or the combination of zanubrutinib and obinutuzumab v Response rate in relationship to molecular and genetic prognostic factors vi Immunological recovery vii Overall survival OS viii Biomarkers for response
Arm A Patients will be treated with the combination of zanubrutinib 320 mg PO qDay and obinutuzumab starting obinutuzumab at cycle 2 to reduce infusion-related reactions Intravenous obinutuzumab will be given on days 1 100 mg 2 900 mg 8 1000 mg and 15 1000 mg of cycle 2 and on day 1 1000 mg of cycles 3-7
Arm B Patients will start treatment with zanubrutinib 320 mg PO qDay in monotherapy After 12 cycles of zanubrutinib patients will be treated with the combination of zanubrutinib and obitnutuzumab Intravenous obinutuzumab will be given on days 1 100 mg 2 900 mg 8 1000 mg and 15 1000 mg of cycle 13 and on day 1 1000 mg of cycles 14-18
Response will be assessed after 20 cycles of treatment for the primary objective of the study Patients that in the evaluation of cycle 20 who achieve uMRD 001 tumour cells by flow cytometry will stop treatment with zanubrutinib whereas the rest of patients will continue on treatment with zanubrutinib until progression unacceptable toxicity or trial completion whichever comes first Patients who achieve an uMRD in bone marrow beyond C20 will also be allowed to stop the treatment whereas the rest of patients will continue on treatment with zanubrutinib until progression unacceptable toxicity or trial completion whichever comes first
In addition the efficacy and safety of the combination therapy with two different administration schedules of obinutuzumab will be analysed through the following outcome measures i Overall response rate including Complete Remission CR CR with incomplete marrow recovery CRi Partial Remission PR and partial response with lymphocytosis ii MRD analysis iiI Duration of response and progression-free survival PFS iv Safety type frequency and severity of adverse events AEs and relationship of AEs to zanubrutinib or the combination of zanubrutinib and obinutuzumab v Response rate in relationship to molecular and genetic prognostic factors vi Immunological recovery vii Overall survival OS viii Biomarkers for response
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None