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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Frankfurter Institut Fuer Klinische Krebsforschung IKF GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23], Diseases [C] - Neoplasms [C04], Diseases [C] - Hemic and Lymphatic Diseases [C15]

Decision date (initial)

2026-04-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

ROCHE Pharma AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

To evaluate the preliminary efficacy of the double T-cell therapy strategy, which includes glofitamab with gemcitabine/oxaliplatin (Glofi-Gem/Ox) prior to and glofitamab monotherapy consolidation after standard of care CAR-T cell therapy.

Secondary objectives 5

1. To further characterize the efficacy of Glofitamab/GemOx induction and Glofitamab consolidation after CAR-T cell therapy.
2. To evaluate the effect of glofitamab consolidation on CAR-T cell expansion, persistence, and functional durability following standard-of-care CAR-T cell therapy
3. To evaluate safety and tolerability of glofitamab/GemOx induction and glofitamab consolidation after CAR-T cell therapy.
4. To determine patient reported outcome of glofitamab/GemOx induction and glofitamab consolidation after CAR-T cell therapy
5. Exploratory analysis of T-cell exhaustion markers and activation profile

Conditions and MedDRA coding

relapsed/refractory Large B-Cell Lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

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: a. Adequate kidney function, defined as: Serum creatinine estimated glomerular filtration rate (MDRD) ≥ 60 mL/min. b. Adequate hepatic function, defined as: ALAT and ASAT ≤ 5 ULN. Bilirubin ≤ 2.0 mg/dl (except for Meulengracht disease) c. Adequate bone marrow function, defined as: Absolute neutrophil count (ANC) ≥ 1000/µL, Platelets ≥ 50.000/µL and Hemoglobin > 8.0 g/dL. d. Adequate cardiac function, defined as: Cardiac ejection fraction ≥ 45%. e. 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.

Exclusion criteria 17

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: a. Surgically cured carcinoma in-situ b. 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 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 18 months after start of trial 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 and to formulate their own wishes correspondingly
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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Complete response rate (CRR) at end of treatment (CCR@EOT), defined as proportion of patients who achieved complete response at the end of trial treatment as per Lugano classification

Secondary endpoints 15

1. CRR post induction treatment (CCR@pIT) and at 3 months post-CAR-T cell infusion (CRR@3MpCT)
2. Overall CRR
3. Objective Response rate (ORR) after induction treatment (ORR@pIT), at 3 months post-CAR-T cell infusion (ORR@3MpCT) and at the end of trial treatment (ORR@EOT)
4. Overall ORR
5. Best overall response rate (BORR)
6. Progression-free survival (PFS) plus PFS rate at one and two years after start of trial treatment
7. Overall survival (OS) plus OS rate at one and two years after start of trial treatment
8. Quantification of peak CAR-T cell expansion in peripheral blood following Glofitamab consolidation (measured by flow cytometry and/or qPCR for CAR transgene)
9. Time to peak CAR-T cell expansion post-infusion
10. Duration of CAR-T cell persistence in peripheral blood (up to end of evaluation period or loss of detectability)
11. Correlation between CAR-T cell expansion/persistence and clinical response (e.g., CR, PR, PFS)
12. 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
13. Incidence of AEs of special Interest (AESIs) as listed in the protocol
14. Tolerability as determined by proportion of patients completing all planned cycles
15. Quality of life over time as determined by EORTC QLQ-C30 questionnaire

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Frankfurter Institut Fuer Klinische Krebsforschung IKF GmbH

Sponsor organisation

Frankfurter Institut Fuer Klinische Krebsforschung IKF GmbH

Address

Steinbacher Hohl 2-26, Praunheim Praunheim

City

Frankfurt Am Main

Postcode

60488

Country

Germany

Scientific contact point

Organisation

Frankfurter Institut Fuer Klinische Krebsforschung IKF GmbH

Contact name

Clinical Trial project manager

Public contact point

Organisation

Frankfurter Institut Fuer Klinische Krebsforschung IKF GmbH

Contact name

Clinical Trial project manager

Third parties 1

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications