Anti-CD7 CAR-T Cells in Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia or Lymphoma

Eligibility Criteria

• 1. Ages 0 to 29 years.
• 2. 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
• 3. Documentation of CD7 expression on leukemic blasts (defined as at least 20% of blasts positive for CD7 by flow cytometry or immunohistochemistry).
• 4. Patients with prior or current history of CNS3 disease will be eligible if CNS disease is responsive to therapy
• 5. Eligible for myeloablative conditioning for and allogeneic HSCT based on the investigator's assessment with an available donor identified by a FACT accredited transplant center.
• 6. 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.
• 7. Patients of childbearing potential must have a negative urine or serum pregnancy test at screening.
• 8. 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.
• 9. Patients (ages ≥ 18 years) or parent/legal guardians (for patients ages \< 18 years) must provide signed, written informed consent according to local IRB and institutional requirements.
• 1. CNS disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
• 2. Clinically active CNS dysfunction or known history of irreversible central neurological toxicity related to prior antileukemic therapy.
• 3. Receipt of prior CD7 targeted therapy.
• 4. Systemic antileukemic therapy intended to induce remission within 14 days prior to completion of screening.
• 5. Radiation therapy within 2 weeks prior to completion of screening, other than prophylaxis for CNS disease.
• 6. Acute 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.
• 7. Undergone HSCT within 90 days prior to completion of screening (or donor leukocyte infusion, if received within 30 days prior to completion of screening).
• 8. Evidence of organ dysfunction including:
• * Serum ALT ≥ 5 × ULN for age
• * Total bilirubin ≥ 3 × ULN for age
• * Serum creatinine that exceeds the maximum values listed in the protocol.
• * Any of the following cardiac criteria:
• * A minimum level of pulmonary reserve defined as \>Grade 1 dyspnea and \>Grade 3 hypoxia; DLCO 40% (corrected for anemia) if PFTs are clinically appropriate as determined by the investigator
• 9. 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 Ag or positive core Ab unless Hep B DNA negative by polymerase chain reaction \[PCR\])
• * Hepatitis C (if hepatitis C virus \[HCV\] antibody positive) must be HCV 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.
• 10. Uncontrolled, active bacterial, viral, or fungal infection.
• 11. Any other condition that would make the patient ineligible for HSCT as determined by the investigator.
• 12. Patients with an autoimmune disorder requiring systemic immunosuppressive therapy that cannot be safely withheld for 3 months.
• 13. 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.
• 14. Known primary immunodeficiency or BM failure syndrome.
• 15. Pregnant or breastfeeding.