B-cell Non Hodgkin LymphomaPhase 1NCT03870945
Safety of MB-CART2019.1 in Lymphoma Patients (MB-CART2019.1 Lymphoma / DALY 1)
A Phase 1 study testing MB-CART2019.1 Dose level 1 and MB-CART2019.1 Dose level 2 in people with B-cell Non Hodgkin Lymphoma, run by Miltenyi Biomedicine GmbH at 3 sites in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- B-cell Non Hodgkin Lymphoma
- What is being tested?
- MB-CART2019.1 Dose level 1 and MB-CART2019.1 Dose level 2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 3 sitesGermany
- Study dates
- 25 Feb 2019to 28 May 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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)
- First line chemo-immunotherapy is defined as therapy containing the combination of CD20 targeted immunotherapy and cytotoxic chemotherapy.
- Chemotherapy-refractory disease is defined as one or more of the following:
- No response to first line of therapy
- PD as best response to first line therapy regimen
- SD as best response after 4 cycles of first line therapy
- Disease progression or relapsed ≤12 months of first line therapy (must have biopsy proven recurrence in relapsed individuals)
- Ineligibility for HSCT is defined as having ONE of the following criteria:
- Age based on country-specific definition
- Impaired pulmonary function (DLCO or FEV1 ≤60%)
- Impaired cardiac function (LVEF <50%)
- Impaired renal function (CrCl <60 mL/min)
- Impaired hepatic function (AST/ALT >3 x ULN, bilirubin >1.5 x ULN or patient's baseline)
- In addition, all patients must fulfil the following criteria:
- Age ≥18 years
- Measurable disease according to Lugano criteria
- CD19 or CD20 tumor expression is not required after first line chemo-immunotherapy.
- Must have archival tissue available, if received CD19 targeted therapy or CD20 antibody, archival tissue must have been obtained subsequent to that therapy
- Must have at least 10 unstained slides of tissue available
- If archival tissue is not available, must be willing to undergo attempted repeat biopsy and fine needle Aspiration
- If has history of CNS disease, then must have:
- No signs or symptoms of CNS disease
- No active disease on magnetic resonance imaging (MRI)
- Absence of large cell lymphoma in cerebral spinal fluid (CSF) on cytospin preparation and flow cytometry, regardless of the number of white blood cells
- If has history of cerebral vascular accident (CVA):
- The CVA event must be >12 months prior to leukapheresis
- Any neurological deficits must be stable
- Estimated life expectancy of >3 months other than primary disease
- No childbearing potential (i.e. postmenopausal, absence of menstrual bleeding for at least 1 year), hysterectomy, bilateral ovariectomy or tubal section/ligation) or negative pregnancy test at screening and before chemotherapy in women of childbearing potential. Sexually active female patients of childbearing potential should use one of the following highly effective methods of contraception (Pearl index <1%): hormonal contraceptives (oral, injected, implanted, transdermal), intrauterine devices or systems (e.g. hormonal and non-hormonal IUD), or vasectomized sexual partner for at least 1 month before the trial start, during the trial and in the 6 months following dosing. Male patients, unless surgically sterile (meaning at least two consecutive analyses following vasectomy demonstrate absence of sperms in the ejaculate), must be using two acceptable methods for contraception (e.g. spermicide and condom) during the trial and refrain from fathering a child throughout the trial and for up to 12 months after dosing
- Signed and dated informed consent before conduct of any trial-specific procedure
Who cannot join
- 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
Show all 27Show fewer
- 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%
- Resting oxygen saturation <90% on room air
- Liver dysfunction as indicated by total bilirubin, AST and/or ALT >5 x institutional ULN, unless directly attributable to patient's tumor
- CrCl <30 mL/min calculated according to the modified formula of Cockcroft and Gault or by direct urine collection
- Pregnant or breast-feeding woman
- Active secondary malignancy requiring treatment
- Medical condition requiring prolonged use of systemic corticosteroids >10 mg/day
- Concurrent radiotherapy (allow up to time of leukapheresis)
- Baseline dementia that would interfere with therapy or monitoring, determined using mini-mental status exam at baseline
- History of severe immediate hypersensitivity reaction against any drug or its ingredients/impurities that is scheduled to be given during trial participation e.g. as part of the mandatory lymphodepletion protocol, premedication for infusion, or rescue medication/salvage therapies for treatment related toxicities
- Patients in which such medication (see exclusion criterion 24) is contraindicated for other reasons than hypersensitivity (e.g. live vaccines and fludarabine)
- Refusal to participate in CAR-T long-term follow-up (LTFU).
- Refusal to undergo core needle biopsy or fine needle aspiration of tumor on day 2-5 after MB-CART infusion and at time of disease progression and relapse
Trial locations and contacts
3 sites in 1 country.
Germany3 sites
Klinikum Augsburg, II. Med. Klinik Haematologie / Onkologie
Augsburg, Bavaria, 86156
University Hospital Cologne - Department for Internal Medicine I
Cologne, North Rhine-Westphalia, 50937
Universitätsklinikum Hamburg-Eppendorf, Department of Stem Cell Transplantation
Hamburg, 20246
About this study
Official title: A Phase I/II Safety, Dose Finding and Feasibility Trial of MB-CART2019.1 in Patients With Relapsed or Resistant B-NHL
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.
Read the detailed description
This trial will be performed as a multi-center phase I/II trial with MB-CART2019.1 and consists of part I. In part I, 12 to 18 patients with relapsed or resistant CD20 and CD19 positive NHL/CLL/SLL will be treated. Six plus three (6+3) patients in dose level 1 and 2 will be treated.
The trial will be conducted in Hematology Departments of Hospitals which meet the structural and personnel requirements for performing the planned regular trial-related investigations. Only sites will be chosen with expertise in and necessary facilities for managing cytokine release storm and other severe adverse events associated with this therapy such as neurotoxicity. A corresponding training to site personnel prior to trial start must be performed. The responsible intensive care unit (ICU) must be informed about the clinical trial before inclusion of the first patient and the respective dosing date in order to make sure that the medical staff of the ICU is able to react appropriately without any loss of time in case of emergency. The University Hospital of Cologne will provide the Coordinating Investigator. Additional clinical sites may be added during the trial.
Patients will be screened between day -30 and day -15. If the patient satisfies all the protocol inclusion and none of the exclusion criteria, he/she will be included in the clinical trial. Leukapheresis will be performed at the collection center on day -14 according to local standard practice. The leukapheresis product of the patient will be shipped by a special courier to the designated manufacturing center assigned by the sponsor. The leukapheresis sample will be used for the individual manufacturing of MB-CART2019.1 by using the automated CliniMACS Prodigy® System. The manufacturing of MB-CART2019.1 will start on day -13 and will be finished on day -1.
On day 5 of the manufacturing process the IPC (in-process-control) will indicate, if the manufacturing process is successful. Therefore, the lymphodepleting chemotherapy must only be started after the positive result of the IPC was confirmed by the manufacturer. Chemotherapy for lymphodepletion will be done on days -5 to -3.
Administration of MB-CART2019.1 will be performed on day 0 in the Hematology Departments of all sites. Patients will be followed up as inpatients until week 4 with close monitoring of their vital functions and lab parameters for signs of adverse events. In the second follow-up phase (week 4 until week 12), response will be assessed, and adverse events will be documented. A follow-up examination will be performed at week 12 (achievement of primary endpoint) and at month 12 which is considered end of trial or end of active part of the trial. In the long-term follow-up yearly until 5 years or patient's death, safety and response assessment as well as persistence of MBCART2019.1 will be performed. These assessments will be analyzed and reported separately and are not part of the entire clinical trial. This is a 6+3 trial design with a 0.3 log dose increment (1x106/2.5x106 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. DLT will be evaluated within 4 weeks after the infusion of MB-CART2019.1. An interval of at least 28 days between the treatment of the first and the second patient in each dose level is mandatory. An observation period for DLT of 28 days is considered to be safe to exclude potential toxicities prior to inclusion of the next patients into the same dose group or prior to dose escalation.
- Conditions
- B-cell Non Hodgkin Lymphoma
- Being tested
- MB-CART2019.1 Dose level 1, MB-CART2019.1 Dose level 2
- Medical subject headings
- Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MB-CART2019.1 Dose level 1Biological
Also called CD2019-targeting CAR T cells, Anti-CD2019 CAR T cells
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.
MB-CART2019.1 Dose level 2Biological
Also called CD2019-targeting CAR T cells, Anti-CD2019 CAR T cells
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Biological: MB-CART2019.1 Dose level 2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Day 28 after infusion of MB-CART2019.1
Secondary outcomes (5)
Preliminary evidence of response to treatment
Objective response rate: (sum of CR+PR), CR, PR, SD and PD is defined according to Lugano criteria (DLBCL, FL. MCL) or IWCLL criteria (CLL/SLL)
Measured: Weeks 4, 12, months 6 and 12 after infusion of MB-CART2019.1
Phenotype and persistence of MB-CART2019.1
Blood samples for determination of persistence/phenotyping of infused MB-CART2019.1 will be analysed
Measured: Days 2, 6, 9; Weeks 2, 3, 4, 6, 8, 12, months 6, 9, and 12 after infusion of MB-CART2019.1
Overall Survival
Determination of Overall Survival rate (OS) after Infusion of MB-CART2019.1
Measured: 12 months after infusion of MB-CART2019.1
Best Overall Response (BOR)
Best Overall Response recorded to study treatment after infusion of MB-CART2019.1 per Investigator assessment
Measured: Weeks 4 + 12, months 6 + 12 after infusion of MB-CART2019.1
Occurence of B-cell aplasia
Assessment of blood samples for occurrence of B cell aplasia
Measured: weeks 2, 4, 8, 12; months 6, 9, 12 after infusion of MB-CART2019.1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2019
- Study start25 Feb 2019
- Primary completion17 Dec 2020
- Study completion28 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for B-cell Non Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by Miltenyi Biomedicine GmbHThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Miltenyi Biomedicine GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- ICON plc
- Responsible party
- Sponsor
- Investigators
- Peter Borchmann, Prof. Dr., Principal investigator, University Hospital of Cologne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03870945
- Sponsor's protocol ID
- M-2018-331
- Status last verified
- May 2025
- First submitted
- 25 Feb 2019
- Last updated
- 28 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Balke-Want H, Godel P, Schmid C, Ayuk F, Friedrichs B, van Heteren P, Holtkamp S, Zadoyan G, Brillant C, Costa J, Hanssens L, Holzer T, Wohle C, Biedermann S, Burger I, Orentas R, Overstijns T, Scheid C, Holtick U, Miltenyi S, Hallek M, 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 Apr 14;10(7):2395-2405. doi: 10.1182/bloodadvances.2025018073.
PubMed 41512222
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Safety, Dose Finding and Feasibility Trial of MB-CART2019.1 in Patients With Relapsed or Resistant B-NHL
- ClinicalTrials.gov ID
- NCT03870945
- Acronym / sponsor ID
- M-2018-331
- Conditions
- B-cell Non Hodgkin Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Miltenyi Biomedicine GmbHIndustry (pharma, biotech, devices)
- Collaborators
- ICON plc
- Study start
- 25 Feb 2019 (actual)
- Primary completion
- 17 Dec 2020 (actual)
- Study completion
- 28 May 2024 (actual)
- First posted
- 12 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This trial will be performed as a multi-center phase I/II trial with MB-CART2019.1 and consists of part I. In part I, 12 to 18 patients with relapsed or resistant CD20 and CD19 positive NHL/CLL/SLL will be treated. Six plus three (6+3) patients in dose level 1 and 2 will be treated.
The trial will be conducted in Hematology Departments of Hospitals which meet the structural and personnel requirements for performing the planned regular trial-related investigations. Only sites will be chosen with expertise in and necessary facilities for managing cytokine release storm and other severe adverse events associated with this therapy such as neurotoxicity. A corresponding training to site personnel prior to trial start must be performed. The responsible intensive care unit (ICU) must be informed about the clinical trial before inclusion of the first patient and the respective dosing date in order to make sure that the medical staff of the ICU is able to react appropriately without any loss of time in case of emergency. The University Hospital of Cologne will provide the Coordinating Investigator. Additional clinical sites may be added during the trial.
Patients will be screened between day -30 and day -15. If the patient satisfies all the protocol inclusion and none of the exclusion criteria, he/she will be included in the clinical trial. Leukapheresis will be performed at the collection center on day -14 according to local standard practice. The leukapheresis product of the patient will be shipped by a special courier to the designated manufacturing center assigned by the sponsor. The leukapheresis sample will be used for the individual manufacturing of MB-CART2019.1 by using the automated CliniMACS Prodigy® System. The manufacturing of MB-CART2019.1 will start on day -13 and will be finished on day -1.
On day 5 of the manufacturing process the IPC (in-process-control) will indicate, if the manufacturing process is successful. Therefore, the lymphodepleting chemotherapy must only be started after the positive result of the IPC was confirmed by the manufacturer. Chemotherapy for lymphodepletion will be done on days -5 to -3.
Administration of MB-CART2019.1 will be performed on day 0 in the Hematology Departments of all sites. Patients will be followed up as inpatients until week 4 with close monitoring of their vital functions and lab parameters for signs of adverse events. In the second follow-up phase (week 4 until week 12), response will be assessed, and adverse events will be documented. A follow-up examination will be performed at week 12 (achievement of primary endpoint) and at month 12 which is considered end of trial or end of active part of the trial. In the long-term follow-up yearly until 5 years or patient's death, safety and response assessment as well as persistence of MBCART2019.1 will be performed. These assessments will be analyzed and reported separately and are not part of the entire clinical trial. This is a 6+3 trial design with a 0.3 log dose increment (1x106/2.5x106 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. DLT will be evaluated within 4 weeks after the infusion of MB-CART2019.1. An interval of at least 28 days between the treatment of the first and the second patient in each dose level is mandatory. An observation period for DLT of 28 days is considered to be safe to exclude potential toxicities prior to inclusion of the next patients into the same dose group or prior to dose escalation.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose level 1 with 1x10^6 MBCART2019.1 per kg BW | Experimental | Biological: MB-CART2019.1 Dose level 1The 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. |
| Dose level 2 with 2.5x10^6 MBCART2019.1 per kg BW | Experimental | Biological: MB-CART2019.1 Dose level 2The 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (44 listed)
- Refractory/relapsed B-NHL (including malignant transformation like Richter's transformation) with no available approved standard therapy. Including, but not restricted to:
- 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:
- First line chemo-immunotherapy is defined as therapy containing the combination of CD20 targeted immunotherapy and cytotoxic chemotherapy.
Key exclusion criteria (27 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MB-CART2019.1 Dose level 1Also: CD2019-targeting CAR T cells, Anti-CD2019 CAR T cellsThis 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. | Biological | Dose level 1 with 1x10^6 MBCART2019.1 per kg BW |
| MB-CART2019.1 Dose level 2Also: CD2019-targeting CAR T cells, Anti-CD2019 CAR T cellsThis 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. | Biological | Dose level 2 with 2.5x10^6 MBCART2019.1 per kg BW |
Primary outcome
Determination of the maximum tolerated dose of MB-CART2019.1
Time frame: Day 28 after infusion 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.
Safety and toxicity assessment of MB-CART2019.1
Time frame: Day 28 after infusion of MB-CART2019.1
Safety and toxicity assessment per AE reporting classified according to CTCAE Version 5.
5 secondary outcomes
Preliminary evidence of response to treatment
Time frame: Weeks 4, 12, months 6 and 12 after infusion of MB-CART2019.1
Phenotype and persistence of MB-CART2019.1
Time frame: Days 2, 6, 9; Weeks 2, 3, 4, 6, 8, 12, months 6, 9, and 12 after infusion of MB-CART2019.1
Overall Survival
Time frame: 12 months after infusion of MB-CART2019.1
Best Overall Response (BOR)
Time frame: Weeks 4 + 12, months 6 + 12 after infusion of MB-CART2019.1
Occurence of B-cell aplasia
Time frame: weeks 2, 4, 8, 12; months 6, 9, 12 after infusion of MB-CART2019.1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2025.
- Derived from this study: PubMed 41512222Balke-Want H, Godel P, Schmid C, Ayuk F, Friedrichs B, van Heteren P, Holtkamp S, Zadoyan G, Brillant C, Costa J, Hanssens L, Holzer T, Wohle C, Biedermann S, Burger I, Orentas R, Overstijns T, Scheid C, Holtick U, Miltenyi S, Hallek M, 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 Apr 14;10(7):2395-2405. doi: 10.1182/bloodadvances.2025018073.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Borchmann, Prof. Dr. principal investigator
University Hospital of Cologne
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MB-CART2019.1 Dose level 1 and MB-CART2019.1 Dose level 2 in people with B-cell Non Hodgkin Lymphoma, run by Miltenyi Biomedicine GmbH at 3 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 44 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determination of the maximum tolerated dose of MB-CART2019.1 (time frame: Day 28 after infusion of MB-CART2019.1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03870945, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2025.