Double-T - Improving Outcomes in High-risk 2nd Line Relapsed/Refractory Large B-Cell Lymphoma Patients Eligible for CAR-T-cell Therapy With a Glofitamab-based Induction and Consolidation Concept

NCT07542678 | Not Yet Recruiting Phase 2

• 2 other identifiers: UKD-IKF-Double-T2025-523806-34-00
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Relapsed /Refractory DLBCL

Outcome Measures

Primary Outcomes (1)

• 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

  at the end of trial treatment, on average after 10 months

Secondary Outcomes (15)

• CCR@pIT and CCR@3MpCT

  post induction (after 6 weeks) and 3 months post-CAR-T cell infusion (after 4,5 months)

• Overall CRR

  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

  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

  from first IMP administration until end of follow-up, on average 2,5 years

• Best overall response (BOR) rate

  from first IMP administration until end of follow-up, on average 2,5 years

Study Arms (1)

Double-T

EXPERIMENTAL

glofitamab with gemcitabine/oxaliplatin (Glofi-Gem/Ox) prior to and glofitamab monotherapy consolidation after standard of care CAR-T cell therapy

Drug: Glofitamab, Gemcitabine, and Oxaliplatin as Induction Therapy; Drug: Glofitamab as Consolidation therapy

Interventions

Glofitamab, Gemcitabine, and Oxaliplatin as Induction Therapy DRUG

Induction Therapy before Standard of Care CAR-T Cell therapy

Double-T

Glofitamab as Consolidation therapy DRUG

Consolidation with Glofitamab after CAR-T Cell Therapy

Double-T

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient\* has given written informed consent.
• Patient is 18-80 years of age at time of signing the written informed consent
• Patient has histologically confirmed diagnosis of large B-cell lymphoma by local pathologist at time of relapse.
• Patient received R-CHOP based first-line therapy containing a CD20-antibody and anthracyclines.
• Patient has relapsed/refractory disease, defined as follows:
• Relapsed: disease that had recurred following partial or complete response (PR/CR) within 12 months of adequate first-line therapy
• Refractory: disease that did not respond to, or that progressed \<6 months after, completion of first-line therapy
• Patient has at least one FDG-PET positive bi-dimensionally measurable (≥1.5 cm) nodal lesion, or one bi dimensionally measurable (\>1 cm extranodal lesion, as measured on computed tomography (CT) scan
• Patient has Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 - 2
• Patient has an absolute lymphocyte count \> 200/µL
• Patient is eligible for CAR-T cell therapy as per investigator´s discretion meeting all of the following criteria of adequate organ function:
• Adequate kidney function, defined as: Serum creatinine estimated glomerular filtration rate (MDRD) ≥ 60 mL/min.
• Adequate hepatic function, defined as: ALAT and ASAT ≤ 5 ULN. Bilirubin
• ≤ 2.0 mg/dl (except for Meulengracht disease)
• Adequate bone marrow function, defined as: Absolute neutrophil count (ANC) ≥ 1000/µL, Platelets ≥ 50.000/µL and Hemoglobin \> 8.0 g/dL.

You may not qualify if:

• Patient has HIV infection of any stage as determined by presence of anti-HIV antibodies (confirmatory test) and / or presence of RNA confirmed by PCR during screening
• Patient has previous or concurrent malignancies with the following exceptions:
• Surgically cured carcinoma in-situ
• Other kinds of cancer without evidence of disease for at least 3 years
• Patient has known hypersensitivity to any component of the Glofitamab, Obinutuzumab, Yescarta and/or Breyanzi formulation formulation as well as a known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein and/or any known contraindication (including hypersensitivity) to one of the other trial drugs
• Patient has severe active infection requiring iv treatment within 14 days prior first dose of study drugs
• Patient has congenital or acquired immunodeficiency including previous organ or allogeneic stem cell transplantation
• Patient received prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3
• Patient received prior treatment with gemcitabine and oxaliplatin in prior lymphoma treatment line
• Patient had a major surgery within 4 weeks prior to first dose of study drugs
• Patient has primary or secondary central nervous system (CNS) lymphoma at the time of enrollment or history of CNS lymphoma
• Patient has current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
• Patient has significant or extensive cardiovascular disease such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 3 months, unstable arrhythmias, or unstable angina
• Patient has an active autoimmune disease requiring systemic treatment
• Patient receives ongoing corticosteroid use \>20 mg/day of prednisone or equivalent. Patients on stable low-dose corticosteroids (≤20 mg/day of prednisone or equivalent for at least 7-14 days prior to first IMP administration) or on short courses of higher-dose corticosteroids that are completed before first IMP administration are eligible.

Sponsors & Collaborators

• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead
• Universitätsklinikum Düsseldorf, Germany: collaborator
• Roche Pharma AG: collaborator

Study Sites (5)

Universitätsklinikum Heidelberg - Innere Medizin V

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Universitätsklinikum Düsseldorf - Klinik für Hämatologie, Onkologie und klinische Immunologie

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

Universitätsklinikum Essen (AöR) - Westdeutsches Tumorzentrum Essen - Klinik für Hämatologie und Stammzellltransplantation

Essen, North Rhine-Westphalia, 45147, Germany

Location

Universitätsklinikum Münster - Medizinische Klinik A

Münster, North Rhine-Westphalia, 48149, Germany

Location

Charité - Universitätsmedizin Berlin - Campus Benjamin Franklin

Berlin, State of Berlin, 12203, Germany

Location

MeSH Terms

Interventions

glofitamab; Gemcitabine; Oxaliplatin; Neoadjuvant Therapy

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Combined Modality Therapy; Therapeutics

Study Officials

• Sascha Dietrich, Prof. Dr.

  University Düsseldorf

  PRINCIPAL INVESTIGATOR

• Salah-Eddin Al-Batran, Prof. Dr.

  Frankfurter Institut für Klinische Krebsforschung IKF GmbH

  STUDY CHAIR

Central Study Contacts

Birte Friedrichs, Dr.

CONTACT

birte.friedrichs@med.uni-duesseldorf.de

Johanna Riedel

CONTACT

double-t@ikf-khnw.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2026
• First Posted: April 21, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2030
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (5)