LUMC-BOB1-B7-TCR.1 in relapsed and refractory B-cell malignancies

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Leids Universitair Medisch Centrum (LUMC)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-08-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The objective of this trial is to determine feasibility, safety and efficacy of LUMC-BOB1-B7-TCR.1 treatment in patients positive for Human
Leukocyte Antigen (HLA)-B*07:02 with relapsed or refractory B-cell malignancies.

Conditions and MedDRA coding

B-cell Acute Lymphoblastic Leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Disease persistence or progression of B-cell Acute Lymphoblastic Leukemia (B-ALL), Multiple Myeloma (MM) or non-Hodgkin B-cell lymphoma without standard treatment options as judged by the treating clinician and by a board of at least two other hematologists of the LUMC
2. Disease entity specific inclusion criteria as specified in the trial protocol
3. Age ≥ 18 years
4. Patients must be able to understand and be willing to give signed informed consent
5. Positive for HLA-B*07:02 according to genotyping results
6. Reliable source of autologous CD8 T cells must be available: o At least 0.03 x 109 CD8+ T cells/L in PB or, alternatively, o Cryopreserved leukapheresis material available that meets all qualification prerequisites as defined by the investigational medicinal product dossier (IMPD)
7. No treatment with other investigational therapeutic product within 3 months prior to IMP infusion
8. No treatment with T-cell engaging bispecific antibodies (BsAbs) within 6 months prior to leukapheresis or, alternatively, no treatment with BsAbs within 2 months prior to the projected date of IMP infusion and availability of cryopreserved leukapheresis material for IMP manufacture harvested prior to start of BsAb treatment
9. In patients with prior Chimeric Antigen Receptor (CAR) therapy: no CAR therapy within 6 months prior to leukapheresis and CAR T cells in PB below limit of detection or, alternatively, availability of cryopreserved leukapheresis material harvested prior to CAR therapy and no CAR therapy within 3 months prior to IMP infusion
10. Eastern Cooperative Oncology Group (ECOG) performance status 0-3
11. Negative pregnancy test in women of childbearing potential
12. For fertile men and women, agreement to use highly effective contraceptive methods for the period between screening and 12 months after IMP infusion

Exclusion criteria 11

1. Pregnant or breast feeding women
2. Active infection with HIV, HBV, HCV or HTLV 1/2
3. Active cerebral localization of B-cell malignancy (cerebral involvement in the past is allowed)
4. Active Graft versus Host Disease requiring current immunosuppression
5. Any clinically significant, advanced or unstable disease or inadequate main organ function that may put the patient at increased risk for severe complications of trial participation at the discretion of the investigator
6. Use of systemic immune suppression including, but not limited to: immunosuppressive agents such as cyclosporine or corticosteroids (at an equivalent dose of 0.5 mg prednisone/kg body weight per day, or higher), inhaled corticosteroids and physiological replacement for adrenal insufficiency are allowed
7. Unwillingness or inability to comply with procedures required in this clinical trial protocol
8. Uncontrolled central nervous system disease
9. Uncontrolled life-threatening infections or uncontrolled disseminated intravascular coagulation; however, if these problems resolve, the start of IMP production and treatment can be initiated on a delayed schedule
10. Known hypersensitivity against any drug of the mandatory trial procedures
11. Has received vaccination with live vaccines 6 weeks prior to treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. Phase 1: The proportion of manufacturing runs from which a LUMCBOB1-B7-TCR.1 drug product was generated at the intended dose.
2. Phase 1: The proportion of included patients that received LUMC-BOB1- B7-TCR.1 treatment.
3. Phase 1: The rate of dose-limiting toxicities (DLTs) within a specific dose cohort until 28 days after LUMC-BOB1-B7-TCR.1 infusion.
4. Phase 1: The maximum tolerated dose evaluated by Bayesian Dose Interval (BOIN) design with a target toxicity rate of 0.3, which is defined as the rate of DLTs within a dose cohort until 28 days after LUMC-BOB1-B7- TCR.1 infusion.
5. Phase 1: The recommended dose for patient treatment in phase 2.
6. Phase 2: Safety and toxicity assessment of LUMC-BOB1-B7-TCR.1 treatment per (serious) adverse event (AE) up to 2 years after infusion, reported according to ASTCT and CTCAE.
7. Phase 2: Response rate 12 weeks after infusion, response is defined as absence of circulating B cells and/or best objective response as defined in literature.

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Leids Universitair Medisch Centrum (LUMC)

Sponsor organisation

Leids Universitair Medisch Centrum (LUMC)

Address

Albinusdreef 2

City

Leiden

Postcode

2333 ZA

Country

Netherlands

Scientific contact point

Organisation

Leids Universitair Medisch Centrum (LUMC)

Contact name

dr. Peter van Balen

Public contact point

Organisation

Leids Universitair Medisch Centrum (LUMC)

Contact name

Susan Collins

Locations

1 EU/EEA country · 1 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

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