Ignite Creation Date:
2024-07-17 @ 11:38 AM
Last Modification Date:
2024-10-26 @ 3:32 PM
Study NCT ID:
NCT06463327
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-17
First Post:
2024-05-08
Brief Title:
ACHIEVE2 - Safety and Preliminary Efficacy of Intravenous TCB008 in Patients With Relapse or Refractory Acute Myeloid Leukemia AML or Myelodysplastic Syndrome MDSAML
Sponsor:
TC Biopharm
Organization:
TC Biopharm
Study Overview
Official Title:
An Open-label Multicenter Phase 1 Study to Evaluate Safety and Preliminary Efficacy of Intravenous TCB008 in Patients With Relapse or Refractory Acute Myeloid Leukemia AML or Myelodysplastic Syndrome MDSAML
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-06
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:
ACHIEVE2
Brief Summary:
TCB008-003 ACHIEVE2 is an open-label multi-center study conducted in 2 parts dose escalation followed by dose expansion to evaluate safety persistenceexpansion and preliminary efficacy of single and multiple intravenous doses of TCB008 in patients with Relapse or Refractory Acute Myeloid Leukemia AML or Myelodysplastic Syndrome MDSAML who have failed or are intolerant to the current standard of care The dose escalation will follow a 33 design with 3 cohorts planned Once the recommended dose for further investigation has been confirmed based on dose-limiting toxicities DLTs overall safety data and preliminary efficacy data up to 20 patients will be enrolled to into one of each of the three dose expansion cohorts
Detailed Description:
TCB008-003 ACHIEVE2 is an open-label multi center study conducted in 2 parts dose escalation followed by dose expansion The purpose of this study is to evaluate Safety and Preliminary Efficacy of Intravenous TCB008 in Patients with Relapse or Refractory Acute Myeloid Leukemia AML or Myelodysplastic Syndrome MDSAML
TCB008 is derived from the peripheral blood mononuclear cells PBMCs of unrelated healthy donors and consists of expanded cluster designation CD3 T cells expressing the γ-chain variable region 9 δ-chain variable region 2 Vγ9Vδ2 T cell receptor TCR it is infused into patients to boost their immune system It is currently developed for treatment of cancers and infectious diseases
Approximately 69 people will take part in this study at several different locations throughout the United States of America
In both parts of the study potential patients will be screened to assess their eligibility to enter the study within 35 days prior to the first dose of the investigational medicinal product IMP Once enrolled in the study patients will undergo lymphodepletion chemotherapy prior to administration of the IMP using the following regimen fludarabine 30 mgm2day will be administered from Days -6 to -3 total 120 mgm2 cyclophosphamide 05 gm2day from Days -5 to -3 total 15 gm2 followed by 2 days of rest Days -2 and -1
The dose escalation part will use a 33 design
The dose escalation part will comprise 3 cohorts of 3 to 6 patients where patients in each cohort will receive up to 4 doses of TCB008 in accordance to the cohort to which they are assigned initial infusion plus 3 potential reinfusions with the following dose-level DL escalating for each cohort
Cohort 1 15 mL IV TCB008 36107 to 69107 cells Cohort 2 up to 5 mL IV TCB008 120107 to 230107 cells Cohort 3 up to 18 mL IV TCB008 432107to 828107 cells
Decisions to escalate the dose will be made on any observed DLTs as well as additional supportive data such as overall safety profile from the 28-day DLT evaluation period following the first infusion with TCB008 for all patients of a cohort The Safety Review Committee SRC with agreement from the sponsor or designee may elect to pursue intermediate lower or higher DLs based on overall review of safety data Alternative dosing schedules may also be considered based on the emerging safety data
The dose expansion part will start once dose escalation has been completed Once the recommended dose for expansion RDE has been confirmed up to 20 patients will be enrolled into one of each of the following dose expansion cohorts
Cohort 4 Patients with relapsed or refractory AML or MDSAML Cohort 5 Patients with previously treated AML or MDSAML who achieved in their last treatment CR with MRD Cohort 6 Patients with previously treated relapse or refractory adverse risk AML or MDSAML per ELN guidelines 2022
For both parts dose escalation and dose expansion patients may be reinfused with TCB008 up to 3 times following initial infusion at the same dose as the initial infusion if deemed appropriate by the investigator or designee based on review of available safety data and confirmation of disease status as defined below
CR was not achieved AML patients following the first dose of TCB008
CR was achieved but MRD is present MRD patients following the first dose of TCB008
patients disease did not progress following administration of previous doses of TCB008
Such reinfusions will not be preceded by lymphodepletion chemotherapy
For both parts dose escalation and dose expansion the study will be conducted as follows
screening period Approximately 4 weeks
lymphodepletion chemotherapy period right before Cycle 1 Approximately 1 week
treatment period Up to 16 weeks from the first dose of IMP TCB008
follow-up period Approximately 24 months from the last dose of IMP TCB008
Patients will be monitored for safety tolerability persistenceexpansion and preliminary efficacy throughout the study Tumor response will be assessed according to ELN 2022 guidelines 28days after the initial infusion and second third and fourth reinfusions as applicable and starting at 6 months 7 days approximately every 3 months 7 days during the follow-up period Optional disease assessment may be performed at the investigator or designees discretion 14 days after the initial infusion and second third and fourth reinfusions as applicable
Patients who discontinue treatment due to other reasons than disease progression will continue with cancer assessments as per protocol until disease progression patient refusal death or starting a new anticancer treatment The total duration of study participation for each patient from screening through end of study visit is anticipated to be approximately 29 months
TCB008 is derived from the peripheral blood mononuclear cells PBMCs of unrelated healthy donors and consists of expanded cluster designation CD3 T cells expressing the γ-chain variable region 9 δ-chain variable region 2 Vγ9Vδ2 T cell receptor TCR it is infused into patients to boost their immune system It is currently developed for treatment of cancers and infectious diseases
Approximately 69 people will take part in this study at several different locations throughout the United States of America
In both parts of the study potential patients will be screened to assess their eligibility to enter the study within 35 days prior to the first dose of the investigational medicinal product IMP Once enrolled in the study patients will undergo lymphodepletion chemotherapy prior to administration of the IMP using the following regimen fludarabine 30 mgm2day will be administered from Days -6 to -3 total 120 mgm2 cyclophosphamide 05 gm2day from Days -5 to -3 total 15 gm2 followed by 2 days of rest Days -2 and -1
The dose escalation part will use a 33 design
The dose escalation part will comprise 3 cohorts of 3 to 6 patients where patients in each cohort will receive up to 4 doses of TCB008 in accordance to the cohort to which they are assigned initial infusion plus 3 potential reinfusions with the following dose-level DL escalating for each cohort
Cohort 1 15 mL IV TCB008 36107 to 69107 cells Cohort 2 up to 5 mL IV TCB008 120107 to 230107 cells Cohort 3 up to 18 mL IV TCB008 432107to 828107 cells
Decisions to escalate the dose will be made on any observed DLTs as well as additional supportive data such as overall safety profile from the 28-day DLT evaluation period following the first infusion with TCB008 for all patients of a cohort The Safety Review Committee SRC with agreement from the sponsor or designee may elect to pursue intermediate lower or higher DLs based on overall review of safety data Alternative dosing schedules may also be considered based on the emerging safety data
The dose expansion part will start once dose escalation has been completed Once the recommended dose for expansion RDE has been confirmed up to 20 patients will be enrolled into one of each of the following dose expansion cohorts
Cohort 4 Patients with relapsed or refractory AML or MDSAML Cohort 5 Patients with previously treated AML or MDSAML who achieved in their last treatment CR with MRD Cohort 6 Patients with previously treated relapse or refractory adverse risk AML or MDSAML per ELN guidelines 2022
For both parts dose escalation and dose expansion patients may be reinfused with TCB008 up to 3 times following initial infusion at the same dose as the initial infusion if deemed appropriate by the investigator or designee based on review of available safety data and confirmation of disease status as defined below
CR was not achieved AML patients following the first dose of TCB008
CR was achieved but MRD is present MRD patients following the first dose of TCB008
patients disease did not progress following administration of previous doses of TCB008
Such reinfusions will not be preceded by lymphodepletion chemotherapy
For both parts dose escalation and dose expansion the study will be conducted as follows
screening period Approximately 4 weeks
lymphodepletion chemotherapy period right before Cycle 1 Approximately 1 week
treatment period Up to 16 weeks from the first dose of IMP TCB008
follow-up period Approximately 24 months from the last dose of IMP TCB008
Patients will be monitored for safety tolerability persistenceexpansion and preliminary efficacy throughout the study Tumor response will be assessed according to ELN 2022 guidelines 28days after the initial infusion and second third and fourth reinfusions as applicable and starting at 6 months 7 days approximately every 3 months 7 days during the follow-up period Optional disease assessment may be performed at the investigator or designees discretion 14 days after the initial infusion and second third and fourth reinfusions as applicable
Patients who discontinue treatment due to other reasons than disease progression will continue with cancer assessments as per protocol until disease progression patient refusal death or starting a new anticancer treatment The total duration of study participation for each patient from screening through end of study visit is anticipated to be approximately 29 months
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