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

A Phase I Safety, Dose Finding and Feasibility Trial of MB-CART19.1 in Patients With Relapsed or Refractory CD19 Positive B Cell Malignancies

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).

Study Overview

• Status: Active, not recruiting
• Conditions: B-cell Lymphoma Refractory; B-cell Lymphoma Recurrent; Acute Lymphoblastic Leukemia Recurrent; Chronic Lymphocytic Leukemia Recurrent; Chronic Lymphocytic Leukemia Refractory
• Intervention / Treatment: Biological: MB-CART19.1

Detailed Description

This trial will evaluate the safety of the MB-CART19.1 and determine the recommended dose levels for each of the three disease cohorts.

Dose evaluation will start in Cohorts 1 and 2 with Dose Level 1 and in Cohort 3 with Dose Level 2, sparing Dose Level 1 (see figure 1). Each of the cohorts will evaluate the safety of MB-CART19.1.

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. 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.

Cohort 3 will Start with Dose Level 2. If Dose Level 2 is not tolerated, Dose Level 1 will be tested. DLT will be evaluated within 4 weeks after the infusion of MB-CART19.1. An interval of at least 28 days between the treatment of the first and the second patient in each dose level (and in each cohort) is mandatory.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Charité - University clinic, pediatric clinic with focus on oncology and hematology
  • Erlangen, Germany, 91054
    • Universitätsklinikum Erlangen
  • Göttingen, Germany, 37075
    • University medicine Goettingen, Clinic of hematology and medical oncology
  • Munich, Germany, 80337
    • Children's Hospital of Dr. von Hauner by Ludwig-Maximilian University
  • Münster, Germany, 48149
    • Universitätsklinikum Münster - Klink für Kinderheilkunde und Jugendmedizin / Pädiatrische Hämatologie und Onkologie
  • Münster, Germany, 48149
    • Universitätsklinikum Münster - Medizinische Klinik A / KMT Zentrum
  • Tübingen, Germany, 72076
    • Tuebingen University clinic, medical university clinic for internal medicine
  • Tübingen, Germany, 72076
    • University clinic for children and youth medicine
  • Würzburg, Germany, 97070
    • University clinic, pediatric hematology and oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.
• ALL patients with combined bone marrow and CNS and/or testicular relapse are eligible only if the extramedullary disease has been successfully cleared by conventional therapy at the time of inclusion (e.g. intrathecal chemotherapy, orchiectomy).

Pediatric aggressive NHL (1-17 years):

• patients after at least one salvage chemotherapy as bridge to alloSCT or
• patients ineligible for alloSCT or
• patients who have relapsed post alloSCT at least 100 days posttransplant, with not evidence of active GVHD, and no longer taking immunosuppressive agents for at least 30 days prior to enrollment.
• patients with CNS disease (excluding isolated CNS lymphoma) are eligible only if disease has been successfully cleared by intrathecal chemotherapy at the time of inclusion.

Adult NHL:

• patients after at least one standard chemotherapy and one salvage regimen as bridge to alloSCT or
• patients who are ineligible for alloSCT 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 CNS disease (excluding isolated CNS lymphoma) are eligible only if disease has been successfully cleared by intrathecal chemotherapy at the time of inclusion.

CLL:

• patients with r/r disease after established and approved treatment options have failed.
• patients not eligible or appropriate for conventional alloSCT.

Exclusion Criteria:

• 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,
  • Alemtuzumab within 3 months prior to leukapheresis,
  • Exception: Intrathecal chemotherapy is allowed prior to treatment, but should be discontinued in ALL and BL 10 days prior to MB-CART19.1 infusion to limit risk of neurotoxicities;
• Hypersensitivity against any drug or its ingredients/impurities that is scheduled or likely to be given during trial participation, e.g. as part of the mandatory lymphodepletion protocol, pre-medication for infusion, rescue medication/salvage therapies for treatment related toxicities;
• Intake of concomitant medication contraindicated for other reasons than hypersensitivity, e.g. live vaccines and fludarabine;
• Contraindication of trial related procedures as judged by the investigator, e.g. lumbar punctures for CSF sampling;
• Female patients of child-bearing potential not willing to practice a highly effective form of birth control from the time of enrollment and for 12 months after dosing the IMP;
• Male patients of fathering potential not willing to practice a highly effective form of birth control from the time of enrollment and for 12 months after dosing the IMP;
• Concurrent participation in another interventional trial that could interact with this trial, e.g. CAR T trials;
• Cerebral dysfunction, legal incapacity of adult patients;
• Committal to an institution on judicial or official order.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DL 0: 1x10e5 MB-CART19.1 cells; 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; 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; Other Names: CD19-targeting CAR T cells; Anti-CD19 CAR T cells
Experimental: DL 1: 5x10e5 MB-CART19.1 cells; 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; 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; Other Names: CD19-targeting CAR T cells; Anti-CD19 CAR T cells
Experimental: DL 2: 1x10e6 MB-CART19.1 cells; 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; 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; Other Names: CD19-targeting CAR T cells; Anti-CD19 CAR T cells
Experimental: DL 3: 3x10e6 MB-CART19.1 cells; 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; 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; Other Names: CD19-targeting CAR T cells; Anti-CD19 CAR T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall incidence and severity of adverse events	per adverse events (AE) reporting classified according to CTCAE version 5.0	through study completion, an average of 5 years
Response to treatment for each timepoint	ORR in ALL (Rate of CR/CRh)	day 28
Response to treatment for each timepoint	Rate MRD-negative CR in ALL	day 28, week 12, month 6, 1 year
Response to treatment for each timepoint	ORR in NHL/CLL (Rate of CR/PR)	day 28, patients not in CR on day 28: month 3
Occurence of B-cell depletion	Circulating B cell numbers	through study completion, an average of 5 years
Phenotype and persistence of MB-CART19.1	Blood samples for determination of persistence/phenotyping of infused MB-CART19.1 will be analysed	days 2, 7, 10, 14, 28, weeks 8, 12, months 6, 12, 24, 36, 48, 60
Number of patients with successful MB-CART19.1 production	Number of patients meeting the inclusion criteria and none of the exclusion criteria for who an autologous MB-CART19.1 product can be generated	day 0
Rate of ALL patients achieving MRD negative CR	Rate MRD-negative CR in ALL	day 28, week 12, month 6, 1 year
Duration of response	Determination of response rate	through study completion, an average of 5 years
Disease-free survival	disease-free survival at 1 year after adoptive immunotherapy with MB-CART19.1 in patients not receiving alloSCT	at 1 year after MB-CART19.1 infusion in patients not receiving alloSCT
Overall survival	overall survival at 1 year after adoptive immunotherapy with MB-CART19.1 in patients not receiving alloSCT	at 1 year after MB-CART19.1 infusion in patients not receiving alloSCT

Collaborators and Investigators

• Sponsor: Miltenyi Biomedicine GmbH
• Investigators: Principal Investigator: Claudia Rössig, Prof. Dr., Univeristy Hospital Muenster

Study record dates

Study Major Dates

• Study Start (Actual): November 26, 2018
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: February 19, 2019
• First Submitted That Met QC Criteria: February 22, 2019
• First Posted (Actual): February 25, 2019

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Leukemia, B-Cell; Recurrence; Leukemia; Lymphoma; Lymphoma, B-Cell; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: M-2017-322; 2017-002848-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No