Blinatumomab After TCR Alpha Beta/CD19 Depleted HCT

Inclusion Criteria:

• Diagnosis of B-ALL with no evidence of minimal residual disease in the bone marrow bymulti-parameter flow cytometry (FC-MRD negative, <0.01%) and meet at least one of thefollowing:

1. In remission after first relapse or greater (≥ CR2)
2. Very-high risk biology ALL that is proceeding to HCT in first remission (e.g.Induction failure, Severe-hypodiploidy, Ph-like ALL)
3. First remission with persistent disease identified as end of consolidation (EOC)MRD > 0.01%.

• Patients must have an available unrelated or haploidentical donor
• Age ≤ 25 years at time of study enrollment
• Karnofsky Performance Status ≥ 60% for patients 16 years and older and Lansky PlayScore ≥ 60 for patients under 16 years of age
• Have acceptable organ function as defined within 14 days of study registration: Renal:creatinine clearance or radioisotope GFR ≥ 60 mL/min/1.73m2 Hepatic: ALT < 5 x upperlimit of normal (ULN) and total bilirubin ≤ 3 mg/dL Cardiac: left ventricular ejectionfraction ≥ 40% by ECHO/MUGA Pulmonary: No evidence of dyspnea at rest. No supplementaloxygen requirement. If measured, carbon monoxide diffusion capacity (DLCO) > 50%.Central Nervous System: Based on clinical exam, no concern for/evidence of active CNSinfection. Patients with fully treated prior CNS infections are eligible. Patientswith seizure disorders may be enrolled if seizures are well-controlled onanticonvulsant therapy.
• Patients who have experienced their relapse after HCT are eligible, provided they haveno evidence of acute or chronic Graft-versus-Host Disease (GVHD) and are off alltransplant immune suppression therapy for at least 7-days (e.g. steroids,cyclosporine, tacrolimus). Steroid therapy for non-GVHD and/or non-leukemia therapy isacceptable.
• Immunotherapy: At least 42 days after the completion of any type of immunotherapyaside from blinatumomab (e.g. tumor vaccines or CAR T-cell therapy).
• XRT: Cranial or craniospinal XRT is prohibited during protocol therapy. ≥ 90 days musthave elapsed if prior TBI, cranial or craniospinal XRT
• Sexually active females of child bearing potential must agree to use adequatecontraception (diaphragm, birth control pills, injections, intrauterine device [IUD],surgical sterilization, subcutaneous implants, or abstinence, etc.) for the durationof treatment and for 2 months after the completion of blinatumomab therapy. Sexuallyactive men must agree to use barrier contraceptive for the duration of treatment andfor 2 months after the completion of blinatumomab therapy.
• Voluntary written consent before performance of any study-related procedure not partof normal medical care, with the understanding that consent may be withdrawn by thesubject at any time without prejudice to future medical care.
• All patients enrolled in this study must have been enrolled in the BlinatumomabBridging Therapy (BBT) Trial

Exclusion Criteria:

• Active extramedullary disease or presence of chloromatous disease.
• Receiving concomitant chemotherapy, radiation therapy; immunotherapy or otheranti-cancer therapy for treatment of disease other than is specified in the protocol.
• Systemic fungal, bacterial, viral, or other infection not controlled (defined asexhibiting ongoing signs/symptoms related to the infection and without improvement,despite appropriate antibiotics or other treatment). Patients with possible fungalinfections must have had at least 2 weeks of appropriate anti-fungal antibiotics andbe asymptomatic.
• Pregnant or lactating. The agents used in this study are known to be teratogenic to afetus and there is no information on the excretion of agents into breast milk. Allfemales of childbearing potential must have a blood test or urine study within 7 daysprior to registration to rule out pregnancy.
• Known allergy to any chemotherapies or targeted agents included in this protocol.
• Participating in a concomitant Phase 1 or 2 study involving treatment of disease.
• Active malignancy other than B-ALL.