Genetically Engineered Cells (BEAM-201) for the Treatment of Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia or T-Cell Lymphoblastic Lymphoma

Inclusion Criteria

• Ages 0 to 29 years
• T-ALL/T-LLy in second or greater relapse, first relapse post-transplant, or chemotherapy-refractory disease. Specifically: * Second or greater relapse or post-transplant relapse, defined as: ** BM with ≥ 5% lymphoblasts by morphologic assessment or evidence of extramedullary disease after second documented CR; OR ** Flow cytometric confirmation of relapsed T-ALL of at least 0.1% after second CR documented to have been MRD negative < 0.1%; OR ** Any detectable relapsed disease post-allogeneic HSCT with flow cytometric confirmation of T-ALL of at least 0.1%; OR ** Biopsy confirmed evidence of relapsed T-LLy after second CR; OR ** Any detectable disease post-allogeneic transplant with biopsy confirmed evidence of T-LLy * Refractory disease, defined as: ** Primary refractory T-ALL or T-LLy, defined as failure to achieve CR after induction chemotherapy, per investigator assessment and based on biopsy-or MRD-confirmed evidence of residual T-ALL or T-LLy; OR ** Relapsed, refractory disease, defined as > 0.1 % MRD or morphologic evidence of disease or evidence of residual T-LLy after 1 course of re-induction chemotherapy for patients who have relapsed after previously achieving a CR NOTE: Patients with mixed phenotype acute leukemia with T cell dominant phenotype may be enrolled if the aforementioned criteria are met
• Documentation of CD7 expression on leukemic blasts (defined as at least 90% of blasts positive for CD7 by flow cytometry or immunohistochemistry)
• Patients with prior or current history of central nervous system (CNS)3 disease will be eligible if CNS disease is responsive to therapy
• Eligible for myeloablative conditioning for and allogeneic HSCT based on the investigator’s assessment with an available donor identified by a Foundation for the Accreditation of Cellular Therapy (FACT) accredited transplant center
• Lansky performance status (ages < 16 years at time of consent) or Karnofsky performance status (KPS) (ages ≥ 16 years at time of consent) score of ≥ 50
• Patients of childbearing potential must have a negative urine or serum pregnancy test at screening
• Patients who are sexually active and of reproductive potential must agree to use an acceptable form of highly effective contraception from consent to 12 months after BEAM 201 infusion
• Patients (ages ≥ 18 years) or parent/legal guardians (for patients ages < 18 years) must provide signed, written informed consent according to local Institutional Review Board (IRB) and institutional requirements
• CRITERIA FOR BEAM-201 INFUSION: Disease response: No evidence of high/accelerating disease burden that would, in the opinion of the treating physician, put the subject at significant potential risk for uncontrollable CRS or neurotoxicity
• CRITERIA FOR BEAM-201 INFUSION: Subjects must not have developed new disease complications, deterioration in performance status or overall clinical condition, new laboratory abnormalities, or new toxicities of therapy that would, in the opinion of the investigator, render it unsafe to proceed with BEAM-201 infusion. The following are specific conditions that warrant delaying BEAM-201 infusion: * Pulmonary: New requirement for supplemental oxygen secondary to parenchymal lung disease or presence of progressive radiographic abnormalities on chest x-ray (chest x-ray is not required at this juncture but should be evaluated if performed for clinical purposes) * Cardiac: New cardiac arrhythmia not controlled with medical management. Electrocardiogram (EKG) is not required to evaluate for arrhythmia in the absence of suggestive symptoms or exam findings * Hypotension requiring vasopressor support * Active Infection: Positive blood cultures for bacteria, fungus, or virus within 48 hours of CAR-T cell infusion
• CRITERIA FOR BEAM-201 INFUSION: At least 2 weeks from other investigational treatments
• CRITERIA FOR RETREATMENT: Subjects should not experience a significant change in performance or clinical status compared to their previous study visit that would, in the opinion of the treating physician, increase the risk of experimental cell infusion. Fever may delay or preclude infusion
• CRITERIA FOR RETREATMENT: Subjects with a history of grade 4 CRS or immune effector cell associated neurotoxicity syndrome (ICANS) will only be retreated in the setting of low disease burden at infusion (< M3 marrow)
• CRITERIA FOR RETREATMENT: All toxicities from the prior BEAM-201 treatment should resolve to grade 1 or baseline prior to reinfusion
• CRITERIA FOR RETREATMENT: Subjects experiencing new laboratory abnormalities that in the opinion of the investigator or PI feels may impact subject safety or the subjects’ ability to receive BEAM-201 cells, may have their infusion delayed until both the investigator and principal investigator (PI) determine it is clinically appropriate to proceed with the infusion

Exclusion Criteria

• CNS disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity
• Clinically active CNS dysfunction or known history of irreversible central neurological toxicity related to prior antileukemic therapy
• Receipt of prior CD7 targeted therapy
• Radiation therapy within 2 weeks prior to completion of screening, other than prophylaxis for CNS disease
• Acute graft versus host disease (GVHD) that is grade ≥ 2 and requiring systemic immunosuppression (corticosteroids), or chronic GVHD that is mild, moderate, or severe and requiring systemic immunosuppression (corticosteroids). Grade 1 acute GVHD not requiring immunosuppression is allowable
• Undergone HSCT within 90 days prior to completion of screening (or donor leukocyte infusion, if received within 30 days prior to completion of screening)
• Evidence of organ dysfunction including: * Serum alanine aminotransferase (ALT) ≥ 5 × upper limit of normal (ULN) for age * Total bilirubin ≥ 3 × ULN for age * Serum creatinine that exceeds the maximum values listed below. ** Age: 0 to < 2 years; maximum serum creatinine (mg/dL): 0.6 (male), 06 (female) ** Age: 2 to < 6 years; maximum serum creatinine (mg/dL): 0.8 (male), 0.8 (female) ** Age: 6 to < 10 years; maximum serum creatinine (mg/dL): 1.0 (male), 1.0 (female) ** Age: 10 to < 13 years; maximum serum creatinine (mg/dL): 1.2 (male), 1.2 (female) ** Age: 13 to < 16 years; maximum serum creatinine (mg/dL): 1.5 (male), 1.4 (female) ** Age: >= 16 years; maximum serum creatinine (mg/dL): 1.7 (male), 1.4 (female) * Any of the following cardiac criteria: ** Atrial fibrillation/flutter (not including isolated episodes that responded to medical management) ** Myocardial infarction within the last 12 months ** QT interval corrected for heart rate using Fridericia's method (QTcF) > 480 msec ** Cardiac echocardiography (ECHO) with left ventricular shortening fraction (LVSF) < 30% or left ventricular ejection fraction (LVEF) < 50% or clinically significant pericardial effusion ** Cardiac dysfunction NYHA (New York Heart Association) III or IV * Limited pulmonary reserve defined as > grade 1 dyspnea and > grade 3 hypoxia; diffusion capacity of the lung for carbon monoxide (DLCO) < 40% (corrected for anemia) if pulmonary function tests (PFTs) are clinically appropriate as determined by the investigator
• Positive serology for: * Human immunodeficiency virus (HIV) (HIV-1 or HIV2) * Human T-cell lymphotropic virus (HTLV) (HTLV-1 or HTLV-2) * Hepatitis B (positive surface antigen [Ag] or positive core antibody [Ab] unless hepatitis [hep] B deoxyribonucleic acid [DNA] negative by polymerase chain reaction [PCR]) * Hepatitis C (if hepatitis C virus [HCV] antibody positive) must be HCV ribonucleic acid (RNA) PCR negative. Patients with sustained viral response > 12 weeks following antiviral therapy are eligible as long as no history of hepatic cirrhosis is present
• Uncontrolled, active bacterial, viral, or fungal infection
• Any other condition that would make the patient ineligible for HSCT as determined by the investigator
• Patients with an autoimmune disorder requiring systemic immunosuppressive therapy that cannot be safely withheld for 3 months
• Concurrent use of systemic corticosteroids for diagnoses unrelated to T-ALL/T-LLy is prohibited, with exception of physiologic corticosteroid replacement therapy treatment for adrenal insufficiency
• Known primary immunodeficiency or BM failure syndrome
• Pregnant or breastfeeding