MB-CART19.1 in Relapsed/Refractory Acute Lymphoblastic Leukemia

MB-CART19.1 in Patients With Relapsed/Refractory CD19-positive B Cell Acute Lymphoblastic Leukemia: A Feasibility Study

Single-arm, prospective, open-label feasibility study evaluating the technical and operational feasibility of manufacturing autologous CD19-directed CAR-T cells (MB-CART19.1) at the point of care for the treatment of relapsed or refractory B-ALL in pediatric and adult patients.

Inclusion Criteria:

• Age ≥ 1 year as long as if deemed fit by treating investigator
• CD19 expression must be detected (≥20%) on the malignant cells by flow cytometry.
• Patients with relapsed or refractory disease with 0.01% or higher blasts in the bone marrow, or patients with confirmed disease progression as demonstrated by FDG PET-CT or CT/MRI of the affected lymph node or spleen after at least 2 cycles/lines of chemotherapy are eligible for enrollment. For patients with Philadelphia-positive disease, a second-generation or higher TKI must have been utilized in one of the treatment lines.
• Patients who have relapsed post alloSCT at least 100 days post-transplant, with no evidence of active graft vs host disease, and no longer taking immunosuppressive agents for at least 30 days prior to enrollment.
• Estimated life expectancy > 12 weeks
• Karnofsky or Lansky (age dependent) performance score ≥ 60
• Patients and/or parents must give their written informed consent/assent.
• CNS and/or testicular involvement are allowed, only if cleared and in the presence of systemic involvement.

Exclusion Criteria:

• Rapidly progressive, uncontrolled disease as assessed by the treating physician and/or principal investigator.
• Persistent extramedullary disease.
• Isolated CNS and/or testicular disease.
• Current autoimmune disease, or history of autoimmune disease with potential CNS involvement
• Active hepatitis B, C or HIV
• Active clinically significant CNS dysfunction (including but not limited to uncontrolled seizure disorders, cerebrovascular ischemia or hemorrhage, dementia, paralysis)
• History of an additional malignancy (≤ 3 years) other than non-melanoma skin cancer or carcinoma in situ.
• Pulmonary function: Patients with pre-existing severe lung disease (FEV1 or FVC < 65%) or an oxygen requirement of >28% O2 FiO2 or active pulmonary infection.
• Cardiac function: Left ventricular ejection fraction <50% by echocardiography
• Renal function: Creatinine clearance <50 mL/min/1.73 m2
• Liver function: patients with serum bilirubin ≥3 times upper limit of or AST or ALT > 5 times upper limit of normal, unless due to leukemic liver infiltration as determined by the investigators.
• Pregnant or breast-feeding females
• Medications: systemic chemotherapies, corticosteroids with the exception of physiologic replacement dosing (<0.5 mg/kg/day of methylprednicone), tyrosine kinase inhibitors (TKI) within 7 days prior to leukapheresis, Fludarabine/clofarabine or immunosuppressive drugs and antibodies (e.g. rituximab, blinatumomab) or investigational drugs or donor lymphocyte