Ignite Creation Date:
2024-05-06 @ 12:52 PM
Last Modification Date:
2024-10-26 @ 1:05 PM
Study NCT ID:
NCT03870945
Status:
COMPLETED
Last Update Posted:
2024-04-30
First Post:
2019-02-25
Brief Title:
Safety of MB-CART20191 in Lymphoma Patients MB-CART20191 Lymphoma DALY 1
Sponsor:
Miltenyi Biomedicine GmbH
Organization:
Miltenyi Biomedicine GmbH
Study Overview
Official Title:
A Phase III Safety Dose Finding and Feasibility Trial of MB-CART20191 in Patients With Relapsed or Resistant CD20 and CD19 Positive B-NHL
Status:
COMPLETED
Status Verified Date:
2024-07
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:
None
Brief Summary:
This is a prospective multi-center open phase III trial to evaluate feasibility dosage safety and toxicity as well as efficacy of ex vivo expanded autologous T cells genetically modified to express anti-CD20 and CD19 immunoreceptor MBCART20191 in patients with relapsed or resistant aggressive CD20 and CD19 positive B-NHLCLLSLL
Detailed Description:
This trial will be performed as a multi-center phase III trial with MB-CART20191 and consists of part I In part I 12 to 18 patients with relapsed or resistant CD20 and CD19 positive NHLCLLSLL will be treated Six plus three 63 patients in dose level 1 and 2 will be treated
The trial will be conducted in Hematology Departments of Hospitals which meet the structural and personnel requirements for performing the planned regular trial-related investigations Only sites will be chosen with expertise in and necessary facilities for managing cytokine release storm and other severe adverse events associated with this therapy such as neurotoxicity A corresponding training to site personnel prior to trial start must be performed The responsible intensive care unit ICU must be informed about the clinical trial before inclusion of the first patient and the respective dosing date in order to make sure that the medical staff of the ICU is able to react appropriately without any loss of time in case of emergency The University Hospital of Cologne will provide the Coordinating Investigator Additional clinical sites may be added during the trial
Patients will be screened between day -30 and day -15 If the patient satisfies all the protocol inclusion and none of the exclusion criteria heshe will be included in the clinical trial Leukapheresis will be performed at the collection center on day -14 according to local standard practice The leukapheresis product of the patient will be shipped by a special courier to the designated manufacturing center assigned by the sponsor The leukapheresis sample will be used for the individual manufacturing of MB-CART20191 by using the automated CliniMACS Prodigy System The manufacturing of MB-CART20191 will start on day -13 and will be finished on day -1
On day 5 of the manufacturing process the IPC in-process-control will indicate if the manufacturing process is successful Therefore the lymphodepleting chemotherapy must only be started after the positive result of the IPC was confirmed by the manufacturer Chemotherapy for lymphodepletion will be done on days -5 to -3
Administration of MB-CART20191 will be performed on day 0 in the Hematology Departments of all sites Patients will be followed up as inpatients until week 4 with close monitoring of their vital functions and lab parameters for signs of adverse events In the second follow-up phase week 4 until week 12 response will be assessed and adverse events will be documented A follow-up examination will be performed at week 12 achievement of primary endpoint and at month 12 which is considered end of trial or end of active part of the trial In the long-term follow-up yearly until 5 years or patients death safety and response assessment as well as persistence of MBCART20191 will be performed These assessments will be analyzed and reported separately and are not part of the entire clinical trial This is a 63 trial design with a 03 log dose increment 1x10625x106 MBCART20191 per kg BW in a single infusion and maximum 2 dose levels If none or one of the six patients at dose level 1 experiences a dose limiting toxicity another six patients will be treated at dose level 2 If two DLTs are observed at dose level 1 another three patients will be treated with the same dose If more than two DLTs are observed at dose level 1 trial will continue at dose level 0 Dose escalation continues until at least 2 patients among a cohort of six to nine patients experience dose-limiting toxicities or dose level 2 is completed The MTD is defined as the dose level below the dose inducing a DLT in more than 2 patients within one dose level DLT will be evaluated within 4 weeks after the infusion of MB-CART20191 An interval of at least 28 days between the treatment of the first and the second patient in each dose level is mandatory An observation period for DLT of 28 days is considered to be safe to exclude potential toxicities prior to inclusion of the next patients into the same dose group or prior to dose escalation
The trial will be conducted in Hematology Departments of Hospitals which meet the structural and personnel requirements for performing the planned regular trial-related investigations Only sites will be chosen with expertise in and necessary facilities for managing cytokine release storm and other severe adverse events associated with this therapy such as neurotoxicity A corresponding training to site personnel prior to trial start must be performed The responsible intensive care unit ICU must be informed about the clinical trial before inclusion of the first patient and the respective dosing date in order to make sure that the medical staff of the ICU is able to react appropriately without any loss of time in case of emergency The University Hospital of Cologne will provide the Coordinating Investigator Additional clinical sites may be added during the trial
Patients will be screened between day -30 and day -15 If the patient satisfies all the protocol inclusion and none of the exclusion criteria heshe will be included in the clinical trial Leukapheresis will be performed at the collection center on day -14 according to local standard practice The leukapheresis product of the patient will be shipped by a special courier to the designated manufacturing center assigned by the sponsor The leukapheresis sample will be used for the individual manufacturing of MB-CART20191 by using the automated CliniMACS Prodigy System The manufacturing of MB-CART20191 will start on day -13 and will be finished on day -1
On day 5 of the manufacturing process the IPC in-process-control will indicate if the manufacturing process is successful Therefore the lymphodepleting chemotherapy must only be started after the positive result of the IPC was confirmed by the manufacturer Chemotherapy for lymphodepletion will be done on days -5 to -3
Administration of MB-CART20191 will be performed on day 0 in the Hematology Departments of all sites Patients will be followed up as inpatients until week 4 with close monitoring of their vital functions and lab parameters for signs of adverse events In the second follow-up phase week 4 until week 12 response will be assessed and adverse events will be documented A follow-up examination will be performed at week 12 achievement of primary endpoint and at month 12 which is considered end of trial or end of active part of the trial In the long-term follow-up yearly until 5 years or patients death safety and response assessment as well as persistence of MBCART20191 will be performed These assessments will be analyzed and reported separately and are not part of the entire clinical trial This is a 63 trial design with a 03 log dose increment 1x10625x106 MBCART20191 per kg BW in a single infusion and maximum 2 dose levels If none or one of the six patients at dose level 1 experiences a dose limiting toxicity another six patients will be treated at dose level 2 If two DLTs are observed at dose level 1 another three patients will be treated with the same dose If more than two DLTs are observed at dose level 1 trial will continue at dose level 0 Dose escalation continues until at least 2 patients among a cohort of six to nine patients experience dose-limiting toxicities or dose level 2 is completed The MTD is defined as the dose level below the dose inducing a DLT in more than 2 patients within one dose level DLT will be evaluated within 4 weeks after the infusion of MB-CART20191 An interval of at least 28 days between the treatment of the first and the second patient in each dose level is mandatory An observation period for DLT of 28 days is considered to be safe to exclude potential toxicities prior to inclusion of the next patients into the same dose group or prior to dose escalation
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
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