A Phase I dose finding study of MB-CART2219.1 targeting CD19/CD22 in adult and pediatric patients with relapsed/refractory B-cell malignancies

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsklinikum Tuebingen AöR

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

23 Jun 2025 → ongoing

Decision date (initial)

2025-04-01

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The objective of this trial is to assess feasibility, safety of ex vivo generated MB-CART2219.1 in patients with relapsed or refractory CD19 and/or CD22 positive B cell malignancies.

Secondary objectives 12

1. Disease Response (ORR, PR, CR) at 6 months
2. Dose/Response Relation
3. Progression free and overall survival
4. Non-Relapse Mortality
5. Progression-free survival on next line of treatment (PFS-2)
6. Expansion of CAR+ T cells in the peripheral blood and if applicable bone marrow, CSF or other body fluids by flow cytometry
7. Evaluate the level of CD19/CD22-expressing malignant cells in tumor tissue, and if applicable peripheral blood and bone marrow
8. Evaluate the immunophenotype and/or expression profile of MB-CART2219.1 cells and endogenous immune and other hematopoietic cells in the peripheral blood, the bone marrow and/or tumor tissue.
9. Evaluate levels of cytokines, chemokines, and soluble factors in the blood of subjects at baseline and after infusion of MB-CART2219.1 cells
10. Evaluate mechanisms of tumor sensitivity/resistance to MB-CART2219.1 cells Evaluate the development of an anti-CAR cellular immune response after infusion of MB-CART2219.1 cells
11. Efficacy and Toxicity Phase I (Best Overall Response at 6 months, Toxicity CTCAE)
12. Ensure yearly Long-term Follow-up up to 15 years to evaluate OS, PFS, relapse indicence, AESIS, late AEs related to MB-CART2219.1, SARs and secondary malignancies

Conditions and MedDRA coding

Patients with relapsed/refractory Lymphoma or ALL aged ≥ 3 years

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1. For Cohort I Lymphoma, adults: Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
2. Patient or legal gurdian understand and voluntarily sign an informed consent document prior to any study related assessments/procedures.
3. Able to adhere to the study visit schedule and other protocol requirements as well as agrees to continued follow up for up to 15 years as mandated by the regulatory guidelines for gene therapy trials
4. CD19 or CD22 expression must be detected on the malignant cells by flow cytometry or immunohistochemistry. Results of previous assessments after the last treatment with CD19 targeted therapies but preceding inclusion of the patient in this trial are acceptable, if available.
5. Female Subject of childbearing potential and male subjects with female partner of childbearing potential is willing to use highly effective contraceptive methods during treatment until 12 months after IMP exposure. For the purpose of this document, a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm apostmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. For the purpose of this document, a man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. Woman of childbearing potential (WOCBP) must also: - Have a negative pregnancy test as verified by the Investigator, one negative serum beta human chorionic gonadotropin (β-hCG) pregnancy test result at screening, prior to LD chemotherapy. This applies even if the subject practices true abstinence from heterosexual contact. - Perform pregnancy testing on a monthly basis for 12 months after IMP administration. A home test is sufficient. - Agree to abstain from breastfeeding during study participation and for at least 12 months after IMP administration. Male fertile subjects must also: Not donate sperm for at least 12 months following last MB-CART2219.1 infusion.
6. All subjects must agree to refrain from donating blood while on study drug and for 1 year after discontinuation from this study treatment.
7. Male or female patients must have relapsed refractory (r/r) CD19 or CD22 -expressing ALL or Lymphoma/CLL and meet the following disease-specific criteria:
8. Cohort I: Lymphoma (Richter’s Transformation /Burkitt-lymphoma/NHL/CLL), Adults ≥18 years of age: a. patients with r/r lymphoma with following entities according to 5th edtion of the WHO Classification of Haematolymphoid Tumours: -B-lymphoblastic lymphomas -B-Chronic lymphocytic leukemia -Splenic B-cell lymphoma -Marginal zone lymphoma -Follicular lymphoma -Mantle cell lymphoma -Large B-cell lymphoma -Burkitt lymphoma -Transformation from indolent lymphoma after two or more systemic therapies, including one approved in label CAR-T-cell or bispecific antibody treatment option or with contraindications for such treatments. b. patients with r/r CLL after established and approved treatment options including therapy with BTK-inhibitorshave failed. c. patients with lymphoma recommended for autologous or allogeneic stem cell transplant (SCT) therapy by interdisciplinary boards, but not consenting or ineligible for this treatment (including patients with refractory disease precluding alloSCT at this time, which can be included in the study as bridge to alloSCT). d. Patients with with lymphoma relapse after SCT, or after CD19 or CD22 targeting therapies and with confirmed either CD19 or CD22 expression after relapse. e. Patients with CNS involvement by lymphoma are eligible if disease is successfully controlled at the time of inclusion.
9. Cohort II: Acute B-lymphoplastic Leukemia (B-ALL), pediatric patients aged ≥ 12 – 17 years (only opened after substantial amendment and approval of DSMB and authorities upon analysis of dose escalation cohort I: e. Patients with second or later relapse of ALL with >5% blasts in BM or rising molecular failure on two separate measurements and without an approved option for in label CAR-T cells or bispecific or cytotoxic antibody treatment. f. Patients with relapse after SCT or other CD19 or CD22 targeted treatment with confirmed either CD19 or CD22 expression after relapse. g. Patients not consenting or ineligible for allogeneic SCT or have refractory disease activity precluding allogeneic SCT at this time, or h. 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, i. ALL patients with combined bone marrow and CNS and/or testicular relapse are eligible only if the extramedullary disease has been successfully controlled by conventional therapy at the time of inclusion (e.g. intrathecal chemotherapy, orchiectomy). j. Patients with ALL in hematologic remission after induction treatment, but ineligible for full execution of further standardly recommended treatments because of medical or other reasons.
10. For Cohort II ALL, pediatrics: Subject is ≥ 12 years of age at the time of signing ICF.

Exclusion criteria 17

1. Subject received any of the following within the last 7 days of leukapheresis: - Any investigational agent - Immunsupressive medication - Plasmapheresis - Major surgery (as defined by the investigator) - Radiation therapy other than local therapy for underlying malignancy - Use of any systemic anti-neoplastic drug therapy or immune suppressive medication applied for graft-versus-host-disease or other, including the use of high dose steroids e.g. >0,5 mg/kg BW methylprednisolone other than hydrocortisone replacement and other than intermittent topical, inhaled or intranasal corticosteroids which are allowed.
2. Subject has ECOG > 3 at screening for inclusion in the trial
3. Subject has clinical evidence of pulmonary leukostasis, disseminated intravascular coagulation or active graft-versus-host-disease.
4. History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, subarachnoid hemorrhage or other CNS bleed, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
5. Subject has any of the following laboratory abnormalities: − Absolute neutrophil count (ANC) < 500/μL − Absolute lymphocyte count < 200/µL at time of leukapheresis − Platelet count < 50,000 mm3 (platelet transfusion allowed) − Serum Creatinine Clearance (CrCl) < 45 mL/min − Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L) − Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × upper limit of normal (ULN) − Serum total bilirubin > 1.5 × ULN or > 3.0 mg/dL for subjects with documented Gilbert’s syndrome − International ratio (INR) or partial thromboplastin time (PTT) > 1.5 × ULN, or history of Grade ≥ 2 hemorrhage within 30 days, or subject requires ongoing treatment with chronic, therapeutic dosing of anticoagulants (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors)
6. Patient has no adequate vascular access for leukapheresis.
7. Echocardiogram (ECHO) or multi-gated acquisition (MUGA) with left ventricular ejection fraction < 45%.
8. Patient with a history of Class III or IV congestive heart failure (CHF) or severe nonischemic cardiomyopathy, unstable or poorly controlled angina, myocardial infarction, or ventricular arrhythmia within the previous 3 months prior to starting study treatment.
9. Inadequate pulmonary function defined as oxygen saturation (Sa02) < 90 % on room air.
10. Subject has history of primary immunodeficiency.
11. Subject is positive for human immunodeficiency virus (HIV-1), uncontrolled hepatitis B or C or active hepatitis A.
12. Subject with ongoing (incl. controlled) infections or infestations where inclusion of the patient into the clinical trials may significantly jeopardize the health and wellbeing of the patient, as determined by the investigator.
13. Subject with malignancy other than the underlying malignancy in this protocol, unless this disease has been controlled for ≥ 1 year and the exception of the following noninvasive malignancies: − Basal cell carcinoma of the skin − Squamous cell carcinoma of the skin − Carcinoma in situ of the cervix − Carcinoma in situ of the breast − Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is curative.
14. Patient is a female who is pregnant, nursing, or breastfeeding, or who intends to become pregnant during participation in the study.
15. Patient with known hypersensitivity to any component of MB-CART2219.1 product, cyclophosphamide, fludarabine, and/or tocilizumab.
16. Patient has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
17. Patient has any further condition including the presence of further laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The objective of this trial is to assess feasibility, safety and preliminary efficacy of ex vivo generated MB-CART2219.1 in patients with relapsed or refractory CD19 and/or CD22 positive B cell malignancies.

Secondary endpoints 11

1. Disease Response (ORR, PR, CR) at 6 months
2. Dose/Response Relation
3. Progression free and overall survival
4. Non-Relapse Mortality
5. Progression-free survival on next line of treatment (PFS-2)
6. Expansion of CAR+ T cells in the peripheral blood and if applicable bone marrow, CSF or other body fluids by flow cytometry
7. Evaluate the level of CD19/CD22-expressing malignant cells in tumor tissue, and if applicable peripheral blood and bone marrow
8. Evaluate the immunophenotype and/or expression profile of MB-CART2219.1 cells and endogenous immune and other hematopoietic cells in the peripheral blood, the bone marrow and/or tumor tissue.
9. Evaluate levels of cytokines, chemokines, and soluble factors in the blood of subjects at baseline and after infusion of MB-CART2219.1 cells
10. Evaluate mechanisms of tumor sensitivity/resistance to MB-CART2219.1 cells
11. Evaluate the development of an anti-CAR cellular immune response after infusion of MB-CART2219.1 cells

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Tuebingen AöR

Sponsor organisation

Universitaetsklinikum Tuebingen AöR

Address

Geissweg 3, Innenstadt Innenstadt

City

Tuebingen

Postcode

72076

Country

Germany

Scientific contact point

Organisation

Universitaetsklinikum Tuebingen AöR

Contact name

Zentrum für klinische Studien (ZKS)

Public contact point

Organisation

Universitaetsklinikum Tuebingen AöR

Contact name

Zentrum für klinische Studien (ZKS)

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

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