The Double-T trial is a prospective, randomized, single-arm, open-label, multicenter phase II trial investigating a double T-cell therapy strategy, which includes glofitamab with gemcitabine/oxaliplatin (Glofi-Gem/Ox) prior to and glofitamab monotherapy consolidation after standard of care Chimeric Antigen Receptor (CAR)-T cell therapy in high-risk 2nd line relapsed/refractory Large B-Cell Lymphoma (r/r LBCL) patients. Data on safety, efficacy, and quality of life (QoL) will be collected and analyzed.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Induction Therapy before Standard of Care CAR-T Cell therapy
Consolidation with Glofitamab after CAR-T Cell Therapy
Universitätsklinikum Heidelberg - Innere Medizin V
Heidelberg, Baden-Wurttemberg, Germany
Universitätsklinikum Düsseldorf - Klinik für Hämatologie, Onkologie und klinische Immunologie
Düsseldorf, North Rhine-Westphalia, Germany
Universitätsklinikum Essen (AöR) - Westdeutsches Tumorzentrum Essen - Klinik für Hämatologie und Stammzellltransplantation
Essen, North Rhine-Westphalia, Germany
Universitätsklinikum Münster - Medizinische Klinik A
Münster, North Rhine-Westphalia, Germany
Charité - Universitätsmedizin Berlin - Campus Benjamin Franklin
Berlin, State of Berlin, Germany
CRR@EOT
Complete response rate (CRR) at end of treatment (CCR@EOT), defined as proportion of patients who achieved complete response (CR) at the end of trial treatment (EOT) as per Lugano classification
Time frame: at the end of trial treatment, on average after 10 months
CCR@pIT and CCR@3MpCT
CRR post induction (CCR@pIT) and at 3 months post-CAR-T cell infusion (CCR@3MpCT), defined as proportion of patients who achieved complete response after two cycles induction treatment and 3 months after CAR-T cell infusion as per Lugano classification
Time frame: post induction (after 6 weeks) and 3 months post-CAR-T cell infusion (after 4,5 months)
Overall CRR
Overall CRR, defined as proportion of patients who achieved CR as best overall response (BOR)
Time frame: from first Investigational Medicinal Product (IMP) administration until end of follow-up, on average 2,5 years
ORR post induction, at 3 months post-CAR-T cell infusion, and at EOT
Objective Response rate (ORR) post induction (OOR@pIT), at 3 months post-CAR T cell infusion (ORR@3MpCT) and at end of trial treatment (ORR@EOT), defined as proportion of patients who achieved complete or partial response (CR/PR) after 2 cycles of induction treatment, at 3 months after CAR-T cell infusion and at the end of the treatment
Time frame: post induction (after 6 weeks), at 3 months post-CAR-T cell infusion (after 4,5 months), and at end of trial treatment (on average after 10 months)
Overall ORR
Overall ORR, defined as proportion of patients who achieved CR/PR as BOR
Time frame: from first IMP administration until end of follow-up, on average 2,5 years
Best overall response (BOR) rate
Best overall response (BOR) rate
Time frame: from first IMP administration until end of follow-up, on average 2,5 years
PFS
Progression-free survival (PFS) plus PFS rate at one and two years, defined as time from start of treatment until date of progression or death due to any cause
Time frame: from first IMP administration until end of follow-up, on average 2,5 years
OS
Overall survival (OS) plus OS rate at one and two years, defined as time from start of treatment until death due to any cause
Time frame: from first IMP administration until end of follow-up, on average 2,5 years
CAR-T cell expansion
Quantification of peak CAR-T cell expansion in peripheral blood following glofitamab consolidation (measured by flow cytometry and/or qPCR for CAR transgene)
Time frame: from CAR-T Cell infusion until End of treatment visit (on average after 10 months)
Time to peak CAR-T cell expansion post-infusion
Time to peak CAR-T cell expansion post-infusion
Time frame: from CAR-T Cell infusion until End of treatment visit (on average after 10 months)
CAR-T cell persistence
Duration of CAR-T cell persistence in peripheral blood (up to end of evaluation period or loss of detectability)
Time frame: from CAR-T Cell infusion until End of treatment visit (on average after 10 months)
Correlation between CAR-T cell expansion/persistence and clinical response
Correlation between CAR-T cell expansion/persistence and clinical response (e.g., CR, PR, PFS)
Time frame: End of study, after 3 years
Quality of life (QLQ-C30)
Quality of life (QoL) over time as determined by EORTC QLQ-C30 questionnaire. The EORTC QLQ-C30 is a widely used, validated, 30-question, self-report questionnaire designed to assess the quality of life of cancer patients. It covers functional scales, symptom scales, and global health status. The questionnaire uses a Likert scale for responses, typically ranging from 1 ("Not at all") to 4 ("Very much"). Global health status/QoL is scaled from 1 ("very poor") to 7 ("Excellent"). The data collected is used to score 10 subscales, providing a multidimensional overview of a patient's quality of life.
Time frame: From Screening until End of treatment visit (on average after 10 months)
Adverse events
Assessment of safety of the treatment as determined by the incidence, type, causality, frequency, timing, severity and seriousness of adverse events using NCI CTCAE 6.0
Time frame: from first IMP administration until end of follow-up, on average 2,5 years
Adverse events of special interest
Incidence of AEs of special Interest (AESIs) as defined in protocol
Time frame: from first IMP administration until end of follow-up, on average 2,5 years
Proportion of patients completing all planned cycles (Tolerability)
Tolerability as determined by proportion of patients completing all planned cycles
Time frame: from first IMP administration until end of treatment, on average 10 months
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