Ignite Creation Date:
2024-10-26 @ 3:38 PM
Last Modification Date:
2024-10-26 @ 3:38 PM
Study NCT ID:
NCT06572631
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-08-23
Brief Title:
Multi-antigen Specific CD8 T Cells with Decitabine and Lymphodepleting Chemotherapy for the Treatment of Patients with Relapsed or Refractory AML or MDS Following an Allogeneic Hematopoietic Cell Transplantation from a Matched Donor
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Phase 1b Expansion Study of Multi-Antigen Specific CD8 T Cells After Decitabine-enhanced Lymphodepletion an Adoptive Cellular Therapy for Patients with Relapsed or Refractory AML or MDS Following an Allogeneic Hematopoietic Cell Transplantation from Matched HLA Donors
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
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:
This phase I trial tests the safety side effects and best dose of NEXI-001 when given with decitabine and lymphodepleting chemotherapy in treating patients with acute myeloid leukemia AML or myelodysplastic syndrome MDS that has come back after a period of improvement relapsed or that has not responded to previous treatment refractory following an allogeneic hematopoietic cell transplantation from a matched donor NEXI-001 is a type of chimeric antigen receptor T cell therapy in which a patients T cells a type of immune system cell are changed in the laboratory so they will attack cancer cells T cells are taken from a patients blood Then the gene for a special receptor that binds to a certain protein on the patients cancer cells is added to the T cells in the laboratory The special receptor is called a chimeric antigen receptor CAR Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers Decitabine is in a class of medications called hypomethylation agents It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow Lymphodepleting chemotherapy with fludarabine and cyclophosphamide helps kill cancer cells in the body and helps prepare the body for the new CAR-T cells Giving NEXI-001 with decitabine and lymphodepleting chemotherapy may be safe and tolerable in treating patients with relapsed or refractory AML or MDS following an allogeneic hematopoietic cell transplantation from a matched donor
Detailed Description:
PRIMARY OBJECTIVES
I Characterize the safety of allogeneic CD8 leukemia-associated antigens specific T cells NEXI-001 NEXI-001 combined with decitabine
II Determine the recommended phase 2 dose RP2D for NEXI-001 T cells combined with decitabine
SECONDARY OBJECTIVES
I Investigate the preliminary anti-leukemic activity of NEXI-001 T cells combined with decitabine based on
Ia Complete response CR rate Ib Overall response rate ORR Ic Median duration of response Id 1-year overall survival OS Ie 1-year progression-free survival PFS II Cumulative incidence of acute graft-versus-host disease aGVHD of grades 2-4 and 3-4 at day 100 post first infusion of NEXI-001
III Cumulative incidence of chronic graft-versus-host disease cGVHD of all grades at 1 year post first infusion of NEXI-001
IV Characterize the T cells in the NEXI-001 product by immunophenotype and tumor antigen specificity
V Characterize NEXI-001 T cells in peripheral blood PB and bone marrow BM by immunophenotype and tumor antigen specificity
VI Expansion and persistence of NEXI-001 T cells in PB and BM
EXPLORATORY OBJECTIVES
I Evaluate the effect of the following factors on the safety and efficacy of NEXI-001 T cells combined with decitabine
Ia NEXI-001 T-cell immunophenotype Ib Persistence of NEXI-001 T cells in PB and BM Ic Blood levels of the antigen-specific NEXI-001 T cells Id Biomarkers of activation proliferation and exhaustion of T cells Ie The expression of tumor associated antigen TAAs and checkpoint molecules on AML blasts
OUTLINE This is a dose-escalation study of decitabine in combination with NEXI-001 fludarabine and cyclophosphamide
DONOR Donors undergo leukapheresis on study
PATIENTS Patients may receive bridging therapy per standard of care 14 days prior to the start of cycle 1 Patients receive decitabine intravenously IV over 1 hour once per day QD on day -3 -5 or -10 to day -1 lymphodepletion chemotherapy with fludarabine IV over 30 minutes QD and cyclophosphamide IV over 60 minutes QD on day -5 to -3 and then receive NEXI-001 IV over 30 minutes QD on days 1 8 and 15 of cycle 1 Cycles repeat every 33 or 38 days in the absence of disease progression or unacceptable toxicity If NEXI-001 cells remain and treatment criteria are met patients may receive and additional cycle of decitabine IV over 1 hour QD on day -5 to -1 and NEXI-001 IV QD on days 1 8 and 15 in the absence of disease progression or unacceptable toxicity Patients undergo echocardiography ECHO during screening bone marrow aspirate andor bone marrow biopsy positron emission tomography PETcomputed tomography CT scan or magnetic resonance imaging MRI and blood sample collection throughout the study
After completion of study treatment patients are followed up within 30 days and every 3 months for up to 1 year
I Characterize the safety of allogeneic CD8 leukemia-associated antigens specific T cells NEXI-001 NEXI-001 combined with decitabine
II Determine the recommended phase 2 dose RP2D for NEXI-001 T cells combined with decitabine
SECONDARY OBJECTIVES
I Investigate the preliminary anti-leukemic activity of NEXI-001 T cells combined with decitabine based on
Ia Complete response CR rate Ib Overall response rate ORR Ic Median duration of response Id 1-year overall survival OS Ie 1-year progression-free survival PFS II Cumulative incidence of acute graft-versus-host disease aGVHD of grades 2-4 and 3-4 at day 100 post first infusion of NEXI-001
III Cumulative incidence of chronic graft-versus-host disease cGVHD of all grades at 1 year post first infusion of NEXI-001
IV Characterize the T cells in the NEXI-001 product by immunophenotype and tumor antigen specificity
V Characterize NEXI-001 T cells in peripheral blood PB and bone marrow BM by immunophenotype and tumor antigen specificity
VI Expansion and persistence of NEXI-001 T cells in PB and BM
EXPLORATORY OBJECTIVES
I Evaluate the effect of the following factors on the safety and efficacy of NEXI-001 T cells combined with decitabine
Ia NEXI-001 T-cell immunophenotype Ib Persistence of NEXI-001 T cells in PB and BM Ic Blood levels of the antigen-specific NEXI-001 T cells Id Biomarkers of activation proliferation and exhaustion of T cells Ie The expression of tumor associated antigen TAAs and checkpoint molecules on AML blasts
OUTLINE This is a dose-escalation study of decitabine in combination with NEXI-001 fludarabine and cyclophosphamide
DONOR Donors undergo leukapheresis on study
PATIENTS Patients may receive bridging therapy per standard of care 14 days prior to the start of cycle 1 Patients receive decitabine intravenously IV over 1 hour once per day QD on day -3 -5 or -10 to day -1 lymphodepletion chemotherapy with fludarabine IV over 30 minutes QD and cyclophosphamide IV over 60 minutes QD on day -5 to -3 and then receive NEXI-001 IV over 30 minutes QD on days 1 8 and 15 of cycle 1 Cycles repeat every 33 or 38 days in the absence of disease progression or unacceptable toxicity If NEXI-001 cells remain and treatment criteria are met patients may receive and additional cycle of decitabine IV over 1 hour QD on day -5 to -1 and NEXI-001 IV QD on days 1 8 and 15 in the absence of disease progression or unacceptable toxicity Patients undergo echocardiography ECHO during screening bone marrow aspirate andor bone marrow biopsy positron emission tomography PETcomputed tomography CT scan or magnetic resonance imaging MRI and blood sample collection throughout the study
After completion of study treatment patients are followed up within 30 days and every 3 months for up to 1 year
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