Ignite Creation Date:
2024-05-06 @ 3:06 AM
Last Modification Date:
2024-10-26 @ 11:28 AM
Study NCT ID:
NCT02203903
Status:
RECRUITING
Last Update Posted:
2023-09-21
First Post:
2014-07-25
Brief Title:
Multi-institutional Prospective Research of Expanded Multi-antigen Specifically Oriented Lymphocytes for the Treatment of VEry High Risk Hematopoietic Malignancies
Sponsor:
Catherine Bollard
Organization:
Childrens National Research Institute
Study Overview
Official Title:
Multi-institutional Prospective Phase I Research of Expanded Multi-antigen Specifically Oriented Lymphocytes for the Treatment of VEry High Risk Hematopoietic Malignancies
Status:
RECRUITING
Status Verified Date:
2023-09
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:
RESOLVE
Brief Summary:
This Phase I dose-escalation trial is designed to evaluate the safety of administering rapidly -generated tumor multi-antigen associated -specific cytotoxic T lymphocytes to HSCT recipients Arm A or future HSCT recipients Arm B for the treatment of high-risk or relapsed or refractory hematopoietic malignancies In addition to safety this study will also evaluate if event-free survival EFS is improved with TAA-T administration at six months after HSCT for patients with high risk AML and MDS Arm C
Detailed Description:
This Phase I dose-escalation trial is designed to evaluate the safety of administering rapidly -generated tumor multi-antigen associated -specific cytotoxic T lymphocytes to HSCT recipients Arm A or future HSCT recipients Arm B for the treatment of high-risk or relapsed or refractory hematopoietic malignancies In addition to safety this study will also evaluate if event-free survival EFS is improved with TAA-T administration at six months after HSCT for patients with high risk AML and MDS Arm C
Patients with evidence of high-risk or relapsed or persistent hematopoietic malignancies for example but not limited to acute leukemia lymphoma chronic myeloid leukemia CML chronic myelomonocytic leukemia CMML myelodysplastic syndrome MDS will be eligible for this study Patients will be enrolled at two time points for differing indications in three arms Arm A - post HSCT Arm B- pre HSCT and Arm C for patients with AML or MDS to prevent relapse post HSCT
Because patients with persistent malignancy prior to transplantation have an extremely poor prognosis these patients will be eligible to receive TAA-T before andor after allogeneic hematopoietic stem cell transplantation HSCT Arm B patients will receive autologous TAA-T following a cycle of conventional chemotherapy in an effort to decrease the burden of disease prior to HSCT Patients with persistent disease or high risk for relapse will be eligible to receive planned infusion of allogeneic TAA-T after HSCT given the very high likelihood of relapse and poor outcome on Arm A Patients with high risk AML and MDS who have undergone allo-HSCT and are in a hematologic remission will enroll under Arm C
In all populations we will utilize our established protocol for the manufacture of tumor multi-antigen associated specific cytotoxic T lymphocytes Peripheral blood mononuclear cells will be exposed to antigen presenting cells pulsed with peptides to tumor antigens PRAME WT1 Survivin in a cytokine milieu favorable to T cell expansionactivation inducing selective expansion of T cells targeted to kill tumor cells Patients would be monitored for the development of toxicity In patients with disease at the time of TAA-T infusion efficacy would be evaluated as a secondary endpoint using standard criteria Exploratory investigational analyses would include monitoring of cytokine and cellular milieu pre- and post- TAA-T infusion and in vitro characterization of the host tumor donor lymphocyte product and TAA-T product
For Arm A Patients post-HSCT TAA-T will be infused any time after neutrophil engraftment post-HSCT or day 30 whichever comes first
For Arm B Patients pre-HSCT TAA-T will be infused any time 7 days after previous therapy for relapsed disease
For Arm C Patients post-HSCT TAA-T will be infused any time after neutrophil engraftment post-HSCT or day 30 whichever comes first at dose level 4 Infusions will be within first 5 months post-HSCT
Five different dosing levels will be evaluated Two to four patients will be evaluated on each dosing schedule see below This protocol is designed as a phase I dose-escalation study
Patients will be enrolled to one of the following dosing levels
Dose Level One 5 x 106 cellsm2 Dose Level Two 1 x 107 cellsm2 Dose Level Three 2 x 107 cellsm2 Dose Level Four 4 x 107 cellsm2 Dose Level Five 1 x 108 cellsm2 ONLY applicable to Arm A patients
Arm C patients will ONLY be enrolled at Dose Level Four 4 x 107 cellsm2
Each patient will receive at least one infusion according to the enrolled dose level where the expected volume of infusion is 1 to 10 cc
Patients will receive cells either because of prior refractory disease andor high risk for relapse andor detectable disease at the time of infusion Arm A and Arm B patients will use the dose escalation strategy described above Ideally patients should not receive other systemic antineoplastic agents for at least 45 days after infusion of TAA-T for purposes of evaluation although such treatment may be added if deemed critical for patient care by the attending physician and not under IND Pediatric patients will be enrolled only after the safety analysis has been completed and is acceptable for 2 adult patients in Arm A and B Arm C will enroll pediatric and adult patients
Arm C patients post HSCT T cells will be infused any time after neutrophil engraftment post-HSCT or day 30 whichever comes first but within first 5 months after HSCT on Dose level 4 4x10e7m2
If patients with active disease defined as hematologic relapse or minimal residual disease positive MRD any time after allo-HSCT for Arm A and defined as hematologic relapse or MRD at the time of TAA-T infusion for Arm B and defined as MRD at the time of TAA-T infusion for Arm C do not have grade 3 toxicity that is possibly probably or definitely attributed to TAA-T infusion and fail to rapidly progress with disease requiring urgent therapy patients may receive a subsequent TAA-T cell dose infusion 2 A subsequent dose infusion 2 will also be available for those patients who have stable disease or a mixed partial or complete response including continued complete response by the International Working Group IWG criteria see section 421 at the evaluation after the first TAA-T infusion
Patients who have received at least 2 infusions of TAA-T are eligible to receive up to 6 additional doses infusion 3 to 8 of TAA-T at monthly intervals each of which will consist of the same cell number as their enrolled dose level Patients will not be able to receive additional doses until the initial safety profile is completed at 28 days following the second infusion Notably these doses will be identical to the treated dose for this patient ie no subsequent dose escalation Patients would then receive additional doses starting greater than 28 days from second infusion and be treated at the same dose level as heshe has previously received
Patients with evidence of high-risk or relapsed or persistent hematopoietic malignancies for example but not limited to acute leukemia lymphoma chronic myeloid leukemia CML chronic myelomonocytic leukemia CMML myelodysplastic syndrome MDS will be eligible for this study Patients will be enrolled at two time points for differing indications in three arms Arm A - post HSCT Arm B- pre HSCT and Arm C for patients with AML or MDS to prevent relapse post HSCT
Because patients with persistent malignancy prior to transplantation have an extremely poor prognosis these patients will be eligible to receive TAA-T before andor after allogeneic hematopoietic stem cell transplantation HSCT Arm B patients will receive autologous TAA-T following a cycle of conventional chemotherapy in an effort to decrease the burden of disease prior to HSCT Patients with persistent disease or high risk for relapse will be eligible to receive planned infusion of allogeneic TAA-T after HSCT given the very high likelihood of relapse and poor outcome on Arm A Patients with high risk AML and MDS who have undergone allo-HSCT and are in a hematologic remission will enroll under Arm C
In all populations we will utilize our established protocol for the manufacture of tumor multi-antigen associated specific cytotoxic T lymphocytes Peripheral blood mononuclear cells will be exposed to antigen presenting cells pulsed with peptides to tumor antigens PRAME WT1 Survivin in a cytokine milieu favorable to T cell expansionactivation inducing selective expansion of T cells targeted to kill tumor cells Patients would be monitored for the development of toxicity In patients with disease at the time of TAA-T infusion efficacy would be evaluated as a secondary endpoint using standard criteria Exploratory investigational analyses would include monitoring of cytokine and cellular milieu pre- and post- TAA-T infusion and in vitro characterization of the host tumor donor lymphocyte product and TAA-T product
For Arm A Patients post-HSCT TAA-T will be infused any time after neutrophil engraftment post-HSCT or day 30 whichever comes first
For Arm B Patients pre-HSCT TAA-T will be infused any time 7 days after previous therapy for relapsed disease
For Arm C Patients post-HSCT TAA-T will be infused any time after neutrophil engraftment post-HSCT or day 30 whichever comes first at dose level 4 Infusions will be within first 5 months post-HSCT
Five different dosing levels will be evaluated Two to four patients will be evaluated on each dosing schedule see below This protocol is designed as a phase I dose-escalation study
Patients will be enrolled to one of the following dosing levels
Dose Level One 5 x 106 cellsm2 Dose Level Two 1 x 107 cellsm2 Dose Level Three 2 x 107 cellsm2 Dose Level Four 4 x 107 cellsm2 Dose Level Five 1 x 108 cellsm2 ONLY applicable to Arm A patients
Arm C patients will ONLY be enrolled at Dose Level Four 4 x 107 cellsm2
Each patient will receive at least one infusion according to the enrolled dose level where the expected volume of infusion is 1 to 10 cc
Patients will receive cells either because of prior refractory disease andor high risk for relapse andor detectable disease at the time of infusion Arm A and Arm B patients will use the dose escalation strategy described above Ideally patients should not receive other systemic antineoplastic agents for at least 45 days after infusion of TAA-T for purposes of evaluation although such treatment may be added if deemed critical for patient care by the attending physician and not under IND Pediatric patients will be enrolled only after the safety analysis has been completed and is acceptable for 2 adult patients in Arm A and B Arm C will enroll pediatric and adult patients
Arm C patients post HSCT T cells will be infused any time after neutrophil engraftment post-HSCT or day 30 whichever comes first but within first 5 months after HSCT on Dose level 4 4x10e7m2
If patients with active disease defined as hematologic relapse or minimal residual disease positive MRD any time after allo-HSCT for Arm A and defined as hematologic relapse or MRD at the time of TAA-T infusion for Arm B and defined as MRD at the time of TAA-T infusion for Arm C do not have grade 3 toxicity that is possibly probably or definitely attributed to TAA-T infusion and fail to rapidly progress with disease requiring urgent therapy patients may receive a subsequent TAA-T cell dose infusion 2 A subsequent dose infusion 2 will also be available for those patients who have stable disease or a mixed partial or complete response including continued complete response by the International Working Group IWG criteria see section 421 at the evaluation after the first TAA-T infusion
Patients who have received at least 2 infusions of TAA-T are eligible to receive up to 6 additional doses infusion 3 to 8 of TAA-T at monthly intervals each of which will consist of the same cell number as their enrolled dose level Patients will not be able to receive additional doses until the initial safety profile is completed at 28 days following the second infusion Notably these doses will be identical to the treated dose for this patient ie no subsequent dose escalation Patients would then receive additional doses starting greater than 28 days from second infusion and be treated at the same dose level as heshe has previously received
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
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