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

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 Overview

• Status: Not yet recruiting
• Conditions: Relapsed /Refractory DLBCL
• Intervention / Treatment: Drug: Glofitamab, Gemcitabine, and Oxaliplatin as Induction Therapy; Drug: Glofitamab as Consolidation therapy

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Birte Friedrichs, Dr.; Email: birte.friedrichs@med.uni-duesseldorf.de
• Study Contact Backup: Name: Johanna Riedel; Email: double-t@ikf-khnw.de

Study Locations

• Germany
  • Baden-Wurttemberg
    • Heidelberg, Baden-Wurttemberg, Germany, 69120
      • UNIVERSITÄTSKLINIKUM HEIDELBERG - Innere Medizin V
      • Contact: Peter Dreger, Prof. Dr.
  • North Rhine-Westphalia
    • Düsseldorf, North Rhine-Westphalia, Germany, 40225
      • Universitätsklinikum Düsseldorf - Klinik für Hämatologie, Onkologie und klinische Immunologie
      • Contact: Sascha Dietrich, Prof. Dr.
    • Essen, North Rhine-Westphalia, Germany, 45147
      • Universitätsklinikum Essen (AöR) - Westdeutsches Tumorzentrum Essen - Klinik für Hämatologie und Stammzellltransplantation
      • Contact: Bastian von Tresckow, Prof. Dr.
    • Münster, North Rhine-Westphalia, Germany, 48149
      • Universitätsklinikum Münster - Medizinische Klinik A
      • Contact: Evgenii Shumilov, PD Dr.
  • State of Berlin
    • Berlin, State of Berlin, Germany, 12203
      • Charité - Universitätsmedizin Berlin - Campus Benjamin Franklin
      • Contact: Björn Chapuy, Prof. Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient* has given written informed consent.
2. Patient is 18-80 years of age at time of signing the written informed consent
3. Patient has histologically confirmed diagnosis of large B-cell lymphoma by local pathologist at time of relapse.
4. Patient received R-CHOP based first-line therapy containing a CD20-antibody and anthracyclines.

5. 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
6. 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
7. Patient has Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 - 2
8. Patient has an absolute lymphocyte count > 200/µL

9. Patient is eligible for CAR-T cell therapy as per investigator´s discretion meeting all of the following criteria of adequate organ function:

   1. Adequate kidney function, defined as: Serum creatinine estimated glomerular filtration rate (MDRD) ≥ 60 mL/min.

   2. Adequate hepatic function, defined as: ALAT and ASAT ≤ 5 ULN. Bilirubin

      ≤ 2.0 mg/dl (except for Meulengracht disease)

   3. Adequate bone marrow function, defined as: Absolute neutrophil count (ANC) ≥ 1000/µL, Platelets ≥ 50.000/µL and Hemoglobin > 8.0 g/dL.
   4. Adequate cardiac function, defined as: Cardiac ejection fraction ≥ 45%.
   5. Adequate pulmonary function as per investigators discretion
10. Patient successfully performed MNC-leucapheresis procedure for a commercially available CAR-T-cell product
11. Patient is willing and able to provide baseline biopsy material (archival or fresh tumor sample) for central review
12. Male patients with female partners of childbearing potential are eligible to participate if they agree to contraceptive methods throughout the duration of the trial and at least 18 months after obinutuzumab administration, 12 months after lost dose oxaliplatin, 6 months after lymphodepletion or 2 months after last dose glofitamab, whatever is last
13. Female participants of childbearing potential must agree to use a highly effective method of contraception (e.g., hormonal contraception, intrauterine device (IUD), or surgical sterilization) throughout the duration of the trial and at least 18 months after obinutuzumab administration, 15 months after lost dose oxaliplatin, 6 months after lymphodepletion or 2 months after last dose glofitamab, whatever is last. * There are no data that indicate special gender distribution. Therefore, patients will be enrolled in the trial gender-independently

Exclusion Criteria:

1. 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

2. Patient has previous or concurrent malignancies with the following exceptions:

   1. Surgically cured carcinoma in-situ
   2. Other kinds of cancer without evidence of disease for at least 3 years
3. 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
4. Patient has severe active infection requiring iv treatment within 14 days prior first dose of study drugs
5. Patient has congenital or acquired immunodeficiency including previous organ or allogeneic stem cell transplantation
6. Patient received prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3
7. Patient received prior treatment with gemcitabine and oxaliplatin in prior lymphoma treatment line
8. Patient had a major surgery within 4 weeks prior to first dose of study drugs
9. Patient has primary or secondary central nervous system (CNS) lymphoma at the time of enrollment or history of CNS lymphoma
10. Patient has current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
11. 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
12. Patient has an active autoimmune disease requiring systemic treatment
13. 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.
14. Female patients who are pregnant or breast feeding or planning to become pregnant within up to 18 months after start of treatment. Female patients of childbearing potential must have a negative serum pregnancy test result within 3 days prior to initiation of trial treatment.
15. Patient has a relationship of dependence or employer-employee relationship to the sponsor or the investigator
16. Patient lacks accountability and inability to appreciate the nature, meaning and consequences of the trial

17. Patient is non-compliant, for reasons including, but not limited to the following:

    • Increased alcohol consumption, drug dependency or substance abuse that would interfere with cooperation with requirements of the trial
    • Refusal of blood products during treatment
    • Any similar circumstances that appear to make protocol treatment or follow-up impossible

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Double-T; 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; Induction Therapy before Standard of Care CAR-T Cell therapy; Drug: Glofitamab as Consolidation therapy; Consolidation with Glofitamab after CAR-T Cell Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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)	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	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	from first IMP administration until end of follow-up, on average 2,5 years
Best overall response (BOR) rate	Best overall response (BOR) rate	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	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	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)	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	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)	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)	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.	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	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	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	from first IMP administration until end of treatment, on average 10 months

Collaborators and Investigators

• Sponsor: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
• Collaborators: Roche Pharma AG; Universitätsklinikum Düsseldorf, Germany
• Investigators: Study Chair: Salah-Eddin Al-Batran, Prof. Dr., Frankfurter Institut für Klinische Krebsforschung IKF GmbH; Principal Investigator: Sascha Dietrich, Prof. Dr., University Düsseldorf

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2030

Study Registration Dates

• First Submitted: April 2, 2026
• First Submitted That Met QC Criteria: April 17, 2026
• First Posted (Actual): April 21, 2026

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Combined Modality Therapy; Oxaliplatin; Gemcitabine; Neoadjuvant Therapy; glofitamab
• Other Study ID Numbers: UKD-IKF-Double-T; 2025-523806-34-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No