Ignite Creation Date:
2024-10-26 @ 3:37 PM
Last Modification Date:
2024-10-26 @ 3:37 PM
Study NCT ID:
NCT06552572
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-08-03
Brief Title:
Glofitamab in Relapsed or Refractory Diffuse Large B-cell Lymphoma After CD19 Chimeric Antigen Receptor T-cell Therapy
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Phase II Study of Glofitamab Therapy in Relapsed or Refractory Diffuse Large B-cell Lymphoma Patients Achieving Response After CD19 Chimeric Antigen Receptor T-cell Therapy
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
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:
Glory
Brief Summary:
The objective of this clinical trial is to determine whether the CD20-CD3 bispecific antibody glofitamab is effective in treating residual diffuse large B-cell lymphoma DLBCL in adults who have responded to CD19 Chimeric antigen receptor CAR T-cell therapy for their relapsed or refractory DLBCL Additionally the trial will assess the safety of glofitamab in patients undergoing CD19 CAR T-cell therapy The primary questions to be addressed are
Does glofitamab reduce the number of participants experiencing disease progression following CD19 CAR T-cell therapy What are the medical complications in participants already treated with CD19 CAR T-cell therapy when administered glofitamab
Participants are required to
Receive glofitamab every 21 days for 12 cycles or until disease progression Attend the clinic for checkups and tests every three weeks
Does glofitamab reduce the number of participants experiencing disease progression following CD19 CAR T-cell therapy What are the medical complications in participants already treated with CD19 CAR T-cell therapy when administered glofitamab
Participants are required to
Receive glofitamab every 21 days for 12 cycles or until disease progression Attend the clinic for checkups and tests every three weeks
Detailed Description:
1 Background CD19 CAR T-cell therapy has proven to be a highly effective adoptive cell therapy evidenced by the significant complete response rates in patients with B-cell acute lymphoblastic leukemia B-ALL and large B-cell lymphoma DLBCL leading to FDA approvals While CAR-T cell therapy has been a lifeline for patients unresponsive to other treatments 60 still experience disease progression despite 40 achieving a complete response The durability of remission may be compromised by factors such as loss of the target antigen CD19 inhibitory receptor expression absence of costimulatory ligands limited CAR-T cell expansion or persistence and impaired effector function due to exhaustion Glofitamab a novel bispecific T-cell engaging antibody binds bivalently to CD20 on B-cells and monovalently to CD3 on T-cells Pharmacodynamic studies show that glofitamab administration leads to T-cell activation indicated by increased granzyme B expression suggesting it may alter the tumor immune environment towards T-cell activation We hypothesize that glofitamab could bridge the gap between CAR T- or cytotoxic cells and tumor cells mitigating immune exhaustion This could potentially enhance survival by preventing immune cell exhaustion and boosting the efficacy of immunotherapy Therefore we aim to conduct a prospective study to augment the therapeutic efficacy of CAR-T cells by bolstering effector cells within the tumor immune environment using glofitamab as a subsequent treatment post-CAR-T cell therapy
2 Study population
Patients who show partial response at 1 or 3 months after CD19 CAR T-cell therapy for thier relapsed or refractory DLBCL RR-DLBCL
3 Treatment protocol A Glofitamab every 21 days for 12 cycles or until progression
1 First cycle
Obinutuzumab GPT 1000mg D1
Glofitamab step up dosing 25mg D8 10mg D15
2 After the first cycle completed priming
Glofitamab 30mg IV every 3 weeks B Supportive care
Concomitant administration is recommended during the period of glofitamab administration Changes in dose and duration are at the decision of the investigators
TMP-SMX 400800mg QD
Acyclovir 200-400mg QD
4 Sample sixe - Previous phase II clinical trials of Tixacel associated a treatment response rate of 40-52 in RR-DLBCL a 1-year progression-free survival PFS of 33-44 and a 2-year PFS of 31-36 5 6 The new maintenance treatment group used a better effect than the previous physiotherapy treatment and Tixacel treatment alone setting everyone up Therefore the measurement range H0 S0S1 vs H1 S0S1 S0 S1 According to the definition as the 1-year PFS of the Historical Control group S0 and the test group S1 the 1-year PFS of the Historical Control group was 37 power 90 law level 5 training period 2 years follow-up Assuming that the period of 1 year and the survival time group are exponential under the hypothesis the 1-year PFS of the test group is set to 60 the number of subjects is 28 and the expected event occurrence is 18 With a dropout rate of 5 the final number of registered participants is 30
2 Study population
Patients who show partial response at 1 or 3 months after CD19 CAR T-cell therapy for thier relapsed or refractory DLBCL RR-DLBCL
3 Treatment protocol A Glofitamab every 21 days for 12 cycles or until progression
1 First cycle
Obinutuzumab GPT 1000mg D1
Glofitamab step up dosing 25mg D8 10mg D15
2 After the first cycle completed priming
Glofitamab 30mg IV every 3 weeks B Supportive care
Concomitant administration is recommended during the period of glofitamab administration Changes in dose and duration are at the decision of the investigators
TMP-SMX 400800mg QD
Acyclovir 200-400mg QD
4 Sample sixe - Previous phase II clinical trials of Tixacel associated a treatment response rate of 40-52 in RR-DLBCL a 1-year progression-free survival PFS of 33-44 and a 2-year PFS of 31-36 5 6 The new maintenance treatment group used a better effect than the previous physiotherapy treatment and Tixacel treatment alone setting everyone up Therefore the measurement range H0 S0S1 vs H1 S0S1 S0 S1 According to the definition as the 1-year PFS of the Historical Control group S0 and the test group S1 the 1-year PFS of the Historical Control group was 37 power 90 law level 5 training period 2 years follow-up Assuming that the period of 1 year and the survival time group are exponential under the hypothesis the 1-year PFS of the test group is set to 60 the number of subjects is 28 and the expected event occurrence is 18 With a dropout rate of 5 the final number of registered participants is 30
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