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

A regiszterben nem jelölt feltételek

• Patients must meet all the following criteria to be eligible for enrollment into the study:
• 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.
• 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 or T-LLy blasts (defined as at least 90% of blasts positive for CD7 by flow cytometry or immunohistochemistry).
• Patients with prior or current history of CNS3 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 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.
• Adequate organ function defined as:
  • Adequate Serum creatinine based on age/gender
  • ALT ≤ 5x ULN in the absence of ALL infiltration of the liver
  • Bilirubin ≤ 3 × ULN for age Note: ALT and/or bilirubin results that exceed this range are acceptable if, in the opinion of the physician-investigator (or as confirmed by liver biopsy), the abnormalities are directly related to ALL infiltration of the liver.
  • Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and <Grade 3 hypoxia; DLCO ≥40% (corrected for anemia if necessary) if PFTs are clinically appropriate as determined by the investigator.
  • Cardiac echocardiography (ECHO) with left ventricular shortening fraction (LVSF) ≥ 30% or left ventricular ejection fraction (LVEF) ≥ 50%. In cases where quantitative assessment of LVSF/LVEF is not possible, a statement by the cardiologist that the ECHO shows qualitatively normal ventricular function will suffice
• 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.
  • 4.2 Exclusion Criteria
  • Patients who meet any of the following criteria will be disqualified from entering the study:
• Active hepatitis B or active hepatitis C
• Active HTLV infection
• HIV infection
• Uncontrolled, active bacterial, viral, or fungal infection.
• 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 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).
• Any other condition that would make the patient ineligible for HSCT as determined by the investigator.
• Known primary immunodeficiency or BM failure syndrome.
• Atrial fibrillation/flutter (not including isolated episodes that responded to medical management)
• Clinically significant pericardial effusion
• Myocardial infarction within the last 12 months
• QT interval corrected for heart rate > 480 msec
• Cardiac dysfunction NYHA (New York Heart Association) III or IV
• 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.
• Pregnant or breastfeeding