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

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 >50if ≤16 years old at screening;

• No active Hepatitis B, Hepatitis C, HIV1/2;

• No childbearing potential or negative pregnancy test at screening and beforechemotherapy 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 chemotherapyand 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 noevidence 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 areeligible only if the extramedullary disease has been successfully cleared byconventional 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 notevidence 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 ifdisease has been successfully cleared by intrathecal chemotherapy at the time ofinclusion.

Adult NHL:

• patients after at least one standard chemotherapy and one salvage regimen as bridgeto alloSCT or

• patients who are ineligible for alloSCT or

• patients who have relapsed post alloSCT at least 100 days posttransplant, with noevidence 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 ifdisease has been successfully cleared by intrathecal chemotherapy at the time ofinclusion.

CLL:

• patients with r/r disease after established and approved treatment options havefailed.

• 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 CNSinvolvement;

• Active clinically significant CNS dysfunction (including but not limited touncontrolled seizure disorders, cerebrovascular ischemia or hemorrhage, dementia,paralysis);

• History of an additional malignancy other than non-melanoma skin cancer or carcinomain situ unless disease free for ≥3 years;

• Pulmonary function: Patients with pre-existing severe lung disease or an oxygenrequirement of >28% O2 supplementation or active pulmonary infiltrates on chestX-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 etal. 1976) for patients <18 yrs of age;

• Liver function: Patients with a serum bilirubin >3 times upper limit of normal or anAST or ALT > 5 times upper limit of normal, unless due to leukemic liverinfiltration in the estimation of the investigator;

• Rapidly progressive disease that in the estimation of the investigator wouldcompromise ability to complete study therapy;

• Pregnant or breast-feeding females;

• Medications:

• Systemic chemotherapies, corticosteroids with the exception of physiologicreplacement dosing, tyrosine kinase inhibitors (TKI) within 7 days prior toleukapheresis,

• Fludarabine/clofarabine or immunosuppressive drugs and antibodies (e.g.rituximab, calcineurin inhibitors, blinatumomab) or investigational drugs ordonor lymphocyte transfusions or radiation therapy within 30 days prior toapheresis,

• Alemtuzumab within 3 months prior to leukapheresis,

• Exception: Intrathecal chemotherapy is allowed prior to treatment, but shouldbe discontinued in ALL and BL 10 days prior to MB-CART19.1 infusion to limitrisk of neurotoxicities;

• Hypersensitivity against any drug or its ingredients/impurities that is scheduled orlikely to be given during trial participation, e.g. as part of the mandatorylymphodepletion protocol, pre-medication for infusion, rescue medication/salvagetherapies for treatment related toxicities;

• Intake of concomitant medication contraindicated for other reasons thanhypersensitivity, 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 highlyeffective form of birth control from the time of enrollment and for 12 months afterdosing the IMP;

• Male patients of fathering potential not willing to practice a highly effective formof birth control from the time of enrollment and for 12 months after dosing the IMP;

• Concurrent participation in another interventional trial that could interact withthis trial, e.g. CAR T trials;

• Cerebral dysfunction, legal incapacity of adult patients;

• Committal to an institution on judicial or official order.