MB-CART19.1 r/r CD19+ B-cell Malignancies (BCM)

NCT03853616 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: M-2017-3222017-002848-32
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 9

Brief Summary

This is a phase l multi-centric, single arm, prospective open, dose-escalation study in patients with relapsed or refractory CD19-positive B cell malignancies (ALL, NHL, CLL). The trial will include adult and pediatric patients. In total approximately 48 patients will be included in the trial. There will be three individual cohorts, defined by disease biology: pediatric ALL and aggressive pediatric NHL (Cohort 1), adult ALL (Cohort 2) and adult NHL/CLL (Cohort 3).

Conditions

Acute Lymphoblastic Leukemia Recurrent; B-cell Lymphoma Recurrent; B-cell Lymphoma Refractory; Chronic Lymphocytic Leukemia Recurrent; Chronic Lymphocytic Leukemia Refractory

Outcome Measures

Primary Outcomes (1)

• Determination of the recommended dose of MB-CART19.1

  Maximum tolerated dose (MTD), defined as the highest dose level of the two to three dose levels tested at which \<33% of patients experience DLT until day 28 after infusion of MB-CART19.1, on the basis of safety and toxicity assessment of MB-CART19.1 per adverse events (AE) reporting classified according to CTCAE version 5.0.

  until day 28 after infusion of MB-CART19.1

Secondary Outcomes (11)

• Overall incidence and severity of adverse events

  through study completion, an average of 5 years

• Response to treatment for each timepoint

  day 28

• Response to treatment for each timepoint

  day 28, week 12, month 6, 1 year

• Response to treatment for each timepoint

  day 28, patients not in CR on day 28: month 3

• Occurence of B-cell depletion

  through study completion, an average of 5 years

Study Arms (4)

DL 0: 1x10e5 MB-CART19.1 cells

EXPERIMENTAL

In each dose level of each of the three cohorts three 3 + 3 patients will be treated. A particular dose level will be expanded to 6 patients if one patient out of 3 patients treated at that particular dose level develops DLT. Once this occurs, further dose-escalations are halted until the dose has proven to be safe in the expanded cohort. If 2 or more in a cohort of 6 patients develop DLT no further dose escalation is allowed, and the next lower dose level will be expanded to 6 patients in total. The highest dose among the dose levels tested at which no more than one out of six patients experiences DLT will be considered the MTD.

Biological: MB-CART19.1

DL 1: 5x10e5 MB-CART19.1 cells

EXPERIMENTAL

Dose evaluation will start in Cohorts 1 and 2 with Dose Level 1. In each dose level of each of the three cohorts three 3 + 3 patients will be treated. A particular dose level will be expanded to 6 patients if one patient out of 3 patients treated at that particular dose level develops DLT. Once this occurs, further dose-escalations are halted until the dose has proven to be safe in the expanded cohort. If 2 or more in a cohort of 6 patients develop DLT no further dose escalation is allowed, and the next lower dose level will be expanded to 6 patients in total. The highest dose among the dose levels tested at which no more than one out of six patients experiences DLT will be considered the MTD.

Biological: MB-CART19.1

DL 2: 1x10e6 MB-CART19.1 cells

EXPERIMENTAL

Dose evaluation will start in Cohort 3 with Dose Level 2, sparing Dose Level 1. If Dose Level 2 is not tolerated, Dose Level 1 will be tested. In each dose level of each of the three cohorts three 3 + 3 patients will be treated. A particular dose level will be expanded to 6 patients if one patient out of 3 patients treated at that particular dose level develops DLT. Once this occurs, further dose-escalations are halted until the dose has proven to be safe in the expanded cohort. If 2 or more in a cohort of 6 patients develop DLT no further dose escalation is allowed, and the next lower dose level will be expanded to 6 patients in total. The highest dose among the dose levels tested at which no more than one out of six patients experiences DLT will be considered the MTD.

Biological: MB-CART19.1

DL 3: 3x10e6 MB-CART19.1 cells

EXPERIMENTAL

In each dose level of each of the three cohorts three 3 + 3 patients will be treated. A particular dose level will be expanded to 6 patients if one patient out of 3 patients treated at that particular dose level develops DLT. Once this occurs, further dose-escalations are halted until the dose has proven to be safe in the expanded cohort. If 2 or more in a cohort of 6 patients develop DLT no further dose escalation is allowed, and the next lower dose level will be expanded to 6 patients in total. The highest dose among the dose levels tested at which no more than one out of six patients experiences DLT will be considered the MTD. In Dose Level 3, three additional patients will be treated, if no DLT occurred. Dose Level 0 will be tested only if Dose Level 1 is not tolerable.

Biological: MB-CART19.1

Interventions

MB-CART19.1 BIOLOGICAL

MB-CART19.1 consists of autologous CD19 Chimeric Antigen Receptor (CAR) transduced CD4/CD8 enriched T cells targeting CD19-positive tumor cells in b cell malignancies

Also known as: CD19-targeting CAR T cells, Anti-CD19 CAR T cells

DL 0: 1x10e5 MB-CART19.1 cells; DL 1: 5x10e5 MB-CART19.1 cells; DL 2: 1x10e6 MB-CART19.1 cells; DL 3: 3x10e6 MB-CART19.1 cells

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients must have r/r CD19-expressing ALL or NHL/CLL
• CD19 expression must be detected on the malignant cells by flow cytometry (leukemia, malignant effusion in NHL) or immunohistochemistry (NHL);
• Age ≥ 1 year (if deemed fit by treating investigator);
• Absolute CD3+ T cell count ≥100/μl;
• ECOG performance score of 0-2 if \>16 years old, or Lansky performance score of \>50 if ≤16 years old at screening;
• No active Hepatitis B, Hepatitis C, HIV1/2;
• No childbearing potential or negative pregnancy test at screening and before chemotherapy in women with childbearing potential;
• Signed and dated informed consent/assent by patients
• and meet the following disease-specific criteria:
• ALL:
• patients with \>5% blasts in BM (M2 or M3) after at least one standard chemotherapy and one salvage regimen who are ineligible for allogeneic stem cell transplant (alloSCT) or have refractory disease activity precluding alloSCT at this time, or
• patients who have relapsed post alloSCT at least 100 days posttransplant, with no evidence of active GVHD, and no longer taking immunosuppressive agents for at least 30 days prior to enrollment.
• patients with Ph+ ALL if they are intolerant to tyrosine kinase inhibitor (TKI) therapy, or if they have r/r disease after treatment with at least 2 different TKIs.
• Pediatric aggressive NHL (1-17 years):
• patients after at least one salvage chemotherapy as bridge to alloSCT or

You may not qualify if:

• Isolated CNS or testicular relapse in ALL;
• Isolated CNS lymphomas;
• Active solid brain metastases or history of solid brain metastases
• Current autoimmune disease, or history of autoimmune disease with potential CNS involvement;
• Active clinically significant CNS dysfunction (including but not limited to uncontrolled seizure disorders, cerebrovascular ischemia or hemorrhage, dementia, paralysis);
• History of an additional malignancy other than non-melanoma skin cancer or carcinoma in situ unless disease free for ≥3 years;
• Pulmonary function: Patients with pre-existing severe lung disease or an oxygen requirement of \>28% O2 supplementation or active pulmonary infiltrates on chest X-ray;
• Cardiac function: Fractional shortening \<28% or left ventricular ejection fraction \<50% by echocardiography;
• Renal function: GFR ≤29 mL/min/1.73 m2 by CKD-EPI for patients 18 yrs (Levey et al. 2009) or creatinine clearance ≤29 mL/min/1.73 m2 by Schwartz formula (Schwartz et al. 1976) for patients \<18 yrs of age;
• Liver function: Patients with a serum bilirubin \>3 times upper limit of normal or an AST or ALT \> 5 times upper limit of normal, unless due to leukemic liver infiltration in the estimation of the investigator;
• Rapidly progressive disease that in the estimation of the investigator would compromise ability to complete study therapy;
• Pregnant or breast-feeding females;
• Medications:
• Systemic chemotherapies, corticosteroids with the exception of physiologic replacement dosing, tyrosine kinase inhibitors (TKI) within 7 days prior to leukapheresis,
• Fludarabine/clofarabine or immunosuppressive drugs and antibodies (e.g. rituximab, calcineurin inhibitors, blinatumomab) or investigational drugs or donor lymphocyte transfusions or radiation therapy within 30 days prior to apheresis,

Sponsors & Collaborators

• Miltenyi Biomedicine GmbH: lead

Study Sites (9)

Charité - University clinic, pediatric clinic with focus on oncology and hematology

Berlin, 13353, Germany

Location

Universitätsklinikum Erlangen

Erlangen, 91054, Germany

Location

University medicine Goettingen, Clinic of hematology and medical oncology

Göttingen, 37075, Germany

Location

Children's Hospital of Dr. von Hauner by Ludwig-Maximilian University

Munich, 80337, Germany

Location

Universitätsklinikum Münster - Klink für Kinderheilkunde und Jugendmedizin / Pädiatrische Hämatologie und Onkologie

Münster, 48149, Germany

Location

Universitätsklinikum Münster - Medizinische Klinik A / KMT Zentrum

Münster, 48149, Germany

Location

Tuebingen University clinic, medical university clinic for internal medicine

Tübingen, 72076, Germany

Location

University clinic for children and youth medicine

Tübingen, 72076, Germany

Location

University clinic, pediatric hematology and oncology

Würzburg, 97070, Germany

Location

Study Officials

• Claudia Rössig, Prof. Dr.

  Univeristy Hospital Muenster

  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 19, 2019
• First Posted: February 25, 2019
• Study Start: November 26, 2018
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: April 16, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (9)