Safety of MB-CART2019.1 in Lymphoma Patients (MB-CART2019.1 Lymphoma / DALY 1)

NCT03870945 | Completed Phase 1 DMC

• 1 other identifier: M-2018-331
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

Brief Summary

This is a prospective, multi-center, open phase I/II trial to evaluate feasibility, dosage, safety and toxicity as well as efficacy of ex vivo expanded autologous T cells genetically modified to express anti-CD20 and CD19 immunoreceptor (MBCART2019.1) in patients with relapsed or resistant aggressive CD20 and CD19 positive B-NHL/CLL/SLL.

Conditions

B-cell Non Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• Determination of the maximum tolerated dose of MB-CART2019.1

  Determination of the MTD, defined as the highest dose level at which \<33% of patients experience DLT until day 28 after infusion of MB-CART2019.1 or 2.5x106 MB-CART2019.1 per kg BW, whichever occurs first.

  Day 28 after infusion of MB-CART2019.1

• Safety and toxicity assessment of MB-CART2019.1

  Safety and toxicity assessment per AE reporting classified according to CTCAE Version 5.

  Day 28 after infusion of MB-CART2019.1

Secondary Outcomes (5)

• Preliminary evidence of response to treatment

  Weeks 4, 12, months 6 and 12 after infusion of MB-CART2019.1

• Phenotype and persistence of MB-CART2019.1

  Days 2, 6, 9; Weeks 2, 3, 4, 6, 8, 12, months 6, 9, and 12 after infusion of MB-CART2019.1

• Overall Survival

  12 months after infusion of MB-CART2019.1

• Best Overall Response (BOR)

  Weeks 4 + 12, months 6 + 12 after infusion of MB-CART2019.1

• Occurence of B-cell aplasia

  weeks 2, 4, 8, 12; months 6, 9, 12 after infusion of MB-CART2019.1

Study Arms (2)

Dose level 1 with 1x10^6 MBCART2019.1 per kg BW

EXPERIMENTAL

The IMP will be administered as an intravenous infusion. This is a 6+3 trial arm with 1x10\^6 MBCART2019.1 per kg BW in a single infusion. If none or one of the six patients at dose level 1 experiences a dose limiting toxicity, another six patients will be treated at dose level 2. If two DLTs are observed at dose level 1 another three patients will be treated with the same dose. Dose escalation continues until at least \>2 patients among a cohort of six to nine patients experience dose-limiting toxicities or dose level 2 is completed. The MTD is defined as the dose level below the dose inducing a DLT in more than 2 patients within one dose level.

Biological: MB-CART2019.1 Dose level 1

Dose level 2 with 2.5x10^6 MBCART2019.1 per kg BW

EXPERIMENTAL

The IMP will be administered as an intravenous infusion. This is a 6+3 trial arm with 2.5x10\^6 MBCART2019.1 per kg BW in a single infusion and maximum 2 dose levels. If none or one of the six patients at dose level 1 experiences a dose limiting toxicity, another six patients will be treated at dose level 2. If two DLTs are observed at dose level 1 another three patients will be treated with the same dose. If more than two DLTs are observed at dose level 1, trial will continue at dose level 0. Dose escalation continues until at least \>2 patients among a cohort of six to nine patients experience dose-limiting toxicities or dose level 2 is completed. The MTD is defined as the dose level below the dose inducing a DLT in more than 2 patients within one dose level.

Biological: MB-CART2019.1 Dose level 2

Interventions

MB-CART2019.1 Dose level 1 BIOLOGICAL

This is a prospective, multi-center, open phase I/II trial to evaluate feasibility, dosage, safety and toxicity as well as efficacy of ex vivo expanded autologous T cells genetically modified to express anti-CD20 and CD19 immunoreceptor (MBCART2019.1) in patients with relapsed or resistant aggressive CD20 and CD19 positive B-NHL/CLL/SLL.

Also known as: CD2019-targeting CAR T cells, Anti-CD2019 CAR T cells

Dose level 1 with 1x10^6 MBCART2019.1 per kg BW

MB-CART2019.1 Dose level 2 BIOLOGICAL

This is a prospective, multi-center, open phase I/II trial to evaluate feasibility, dosage, safety and toxicity as well as efficacy of ex vivo expanded autologous T cells genetically modified to express anti-CD20 and CD19 immunoreceptor (MBCART2019.1) in patients with relapsed or resistant aggressive CD20 and CD19 positive B-NHL.

Also known as: CD2019-targeting CAR T cells, Anti-CD2019 CAR T cells

Dose level 2 with 2.5x10^6 MBCART2019.1 per kg BW

Eligibility Criteria

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

You may qualify if:

• Refractory/relapsed B-NHL (including malignant transformation like Richter's transformation) with no available approved standard therapy. Including, but not restricted to:
• Diffuse large B cell lymphoma (DLBCL): relapsed/refractory disease after ASCT or ineligible for ASCT after first-line therapy; transformation from CLL, SLL or FL allowed
• Follicular lymphoma: at least 2 prior regimens and progression \<2 years after most recent line of therapy
• Mantle cell lymphoma: beyond 1st CR with relapsed disease, progressive disease during first-line rituximab chemotherapy, or persistent disease after first-line rituximab-chemotherapy and not eligible or appropriate for conventional therapy, ASCT or relapsed after prior autologous SCT, prior therapies including ibrutinib if not contraindicated
• CLL and SLL: after at least two lines of treatment including btk inhibitor ibrutinib and bcl2 inhibitor venetoclax (if not contraindicated), patients must have been refractory to at least one of the substances
• Patients with criteria 1b-d will only be eligible for Part I, dose cohort 1.
• Patients in cohort 1a must have histologically confirmed DLBCL and associated subtypes with relapse or refractory disease after first line chemo-immunotherapy and be ineligible for HSCT
• Histologically confirmed DLBCL and associated subtypes, defined by WHO 2016 classification:
• DLBCL not otherwise specified (NOS)
• High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (DHL/THL) and FL3B
• Aggressive B-cell lymphoma
• T-cell/histocyte rich B-cell lymphoma
• Primary mediastinal B-cell lymphoma
• EBV+ DLBCL
• Transformed lymphoma (e.g. transformed follicular or marginal zone lymphoma)

You may not qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status \>2
• Absolute neutrophil count (ANC) \<1,000/µL
• Platelet count \<50,000/µL
• Absolute lymphocyte count \<100/µL
• Presence of leukemia/lymphoma cells in peripheral blood
• Primary CNS lymphoma
• Unable to give informed consent
• Known history of infection with human immunodeficiency virus (HIV) or active infection with hepatitis B (HGsAg positive)
• Known history of infection with hepatitis C virus unless treated and confirmed to be polymerase chain reaction (PCR) negative
• Known history or presence of seizure activities or on active anti-seizure medications within the previous 12 months
• Known history of CVA within prior 12 months
• Known history or presence of autoimmune CNS disease, such as multiple sclerosis, optic neuritis or other immunologic or inflammatory disease
• Presence of CNS disease that, in the judgment of the investigator, may impair the ability to evaluate neurotoxicity
• Active systemic fungal, viral or bacterial infection
• Clinical heart failure with New York Heart Association class ≥2 or LVEF \<30%

Sponsors & Collaborators

• Miltenyi Biomedicine GmbH: lead
• ICON plc: collaborator

Study Sites (3)

Klinikum Augsburg, II. Med. Klinik Haematologie / Onkologie

Augsburg, Bavaria, 86156, Germany

Location

University Hospital Cologne - Department for Internal Medicine I

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Universitätsklinikum Hamburg-Eppendorf, Department of Stem Cell Transplantation

Hamburg, 20246, Germany

Location

Related Publications (1)

• Balke-Want H, Godel P, Schmid C, Ayuk FA, Friedrichs B, van Heteren P, Holtkamp S, Zadoyan G, Brillant C, Costa J, Hanssens L, Holzer T, Wohle C, Biedermann S, Burger I, Orentas RJ, Overstijns T, Scheid C, Holtick U, Miltenyi S, Hallek MJ, Borchmann P, Kutsch N. Zamtocabtagene Autoleucel in Relapsed/refractory B-NHL: 5-year Follow Up of a CD20/19 tandem CAR T Cell Phase 1 Trial. Blood Adv. 2026 Jan 9:bloodadvances.2025018073. doi: 10.1182/bloodadvances.2025018073. Online ahead of print.

  PMID: 41512222 DERIVED

MeSH Terms

Conditions

Lymphoma, B-Cell

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Peter Borchmann, Prof. Dr.

  University Hospital Cologne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2019
• First Posted: March 12, 2019
• Study Start: February 25, 2019
• Primary Completion: December 17, 2020
• Study Completion: May 28, 2024
• Last Updated: May 28, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (3)