This is a phase 1, interventional, open label, treatment study designed to evaluate the
safety and feasibility of infusion of CAR-20/19-T in pediatric and young adult subjects with
B cell ALL that have relapsed after prior therapies or refractory disease and are not
candidates for curative intent standard therapy. There will be two phases of this study. A
dose escalation phase to determine the safe CAR-20/19-T cell dose in patients B-cell ALL.
Once the desired dose has been identified there will be a 6-patient dose expansion phase at
the specified dose level.
1. Diagnosis of B-cell ALL: Patients must be aged ≥ 1 years and ≤ 39.99 years with
relapsed or refractory disease and no available curative options that meet clinical
criteria to initiate treatment.
2. Relapsed or refractory B cell ALL defined as one of the following:
1. Primary refractory disease
2. Relapsed or refractory disease after 2 or more lines of systemic therapy
3. Relapsed or refractory disease after allogeneic transplant provided subject is at
least 100 days from stem cell transplant at the time of enrollment and off of
immunosuppressive medications for at least 4 weeks prior to enrollment
3. Morphological disease in the bone marrow (> 5% blasts).
4. Patients with B-cell ALL must have either CD19 or CD20 positive disease on their most
recent bone marrow performed. A minimum of 5% CD19 and/or CD20 positivity on prior or
bone marrow aspirate (BMA) or biopsy is required.
5. Subjects with Ph+ ALL are eligible if they have relapsed or have refractory disease
and have failed two tyrosine kinase inhibitors.
6. Absolute CD3+ T cell count ≥100/mm3.
a. Subjects who receive chemotherapy and/or steroids after CD3+ T-cell count, but
before apheresis, will require this test to be repeated.
7. Lumbar puncture with CSF analysis by cytology with no evidence of disease.
8. Karnofsky/Lansky performance score ≥70. See Appendix A for scales.
9. Normal Baseline Neurological Evaluation: Mini-Mental Status Exam Score 24-30 for > 16
yo (Appendix B).
10. Adequate hepatic function, defined as AST and ALT <3 x upper limit of normal (ULN);
serum bilirubin and alkaline phosphatase <2 x ULN, or considered not clinically
significant as per the clinical PIs discretion (e.g. Gilbert's or indirect
hyperbilirubinemia) or felt to be due to underlying disease.
11. Adequate renal function defined as creatinine clearance or radioisotope GFR > 70
12. Able to give informed consent if > 18 years, or with a legal guardian capable of
giving informed consent if < 18 years.
13. Agree to practice birth control during the study.
14. Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by
15. No clinically significant arrhythmias.
16. Adequate pulmonary function as indicated by room air oxygen saturation of ≥ 92% and no
clinically significant pleural effusion.
17. Expected survival >12 weeks.
18. Negative urine or serum pregnancy test in females of child bearing potential at study
entry and again within 48 hours' prior lymphodepleting chemotherapy.
19. Patients with prior CD19 or CD20 therapy (e.g., blinatumomab, CART19, rituximab)
treatment require repeat BMA/biopsy post-CD19 or CD20 therapy treatment that
demonstrates CD19 or CD20 positive disease.
20. Meet criteria regarding fertility and contraception detailed in section 4.4.
21. Central line access will be required for CAR-20/19-T cell infusion.
1. Positive beta-HCG in female of child-bearing potential defined as per table 1.
2. Patients with known systemic allergy to bovine or murine products.
3. Confirmed active human immunodeficiency virus (HIV), Hepatitis B or C infection. A
history of hepatitis B or hepatitis C is permitted if the viral load is undetectable
per quantitative PCR and/or nucleic acid testing.
4. History of significant autoimmune disease OR active, uncontrolled autoimmune
phenomenon: such as systemic lupus erythematous, Wegner's glomerulonephritis,
autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura (AIHA, ITP) requiring
steroid therapy defined as >20 mg of prednisone.
5. Presence of ≥ grade 3 non-hematologic toxicities as per CTCAE version 5 from any
previous treatment unless it is felt to be due to underlying disease.
6. Concurrent use of investigational therapeutic agents or enrollment on another
therapeutic clinical trial at any institution.
7. Refusal to participate in the long-term follow-up protocol.
8. CNS Abnormalities
1. Patients with prior CNS disease that has been effectively treated will be
eligible providing treatment was >4 weeks before enrollment and a remission
documented within 4 weeks of planned CAR-T cell infusion. Patients will be
excluded if they have any signs of neurotoxicity at baseline or evidence of
chloroma or leukemic infiltrates on MRI.
2. Presence of CNS-3 disease defined as detectable cerebrospinal blast cells in a
sample of CSF with ≥ 5 WBCs per mm3 with or without neurological changes, and
presence of CNS-2 disease defined as detectable cerebrospinal blast cells in a
sample of CSF with < 5 WBCs per mm3 with neurological changes Note: Subjects with
CNS-1 (no detectable leukemia in the CSF) and those with CNS-2 without clinically
evident neurological changes are eligible to participate in the study.
3. History or presence of any CNS disorder, such as a seizure disorder,
cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, any autoimmune
disease with CNS involvement, posterior reversible encephalopathy syndrome
(PRES), or cerebral edema
9. Previous recipients of allogeneic hematopoietic stem cell transplantation (AHCT) are
excluded if they are <100 days' post-transplant, have evidence of active
graft-versus-host-disease (GVHD) of any grade, or are currently on immunosuppression.
10. Anti-CD20 antibody treatment within 4 weeks of cell infusion.
11. Anti-CD19 antibody treatment within 4 weeks of cell infusion
12. Cytotoxic chemotherapy other than lymphodepletion within 14 days of CAR-T cell
13. Cytotoxic chemotherapy treatment within 14 days or steroid treatment (other than
replacement dose steroids) within 7 days prior to apheresis collection for CAR-T
cells. TKIs must be held for 5 half lives or 7 days whichever is shorter prior to
14. Patients post solid organ transplant who develop high grade lymphomas or leukemias.
15. Concurrent active malignancy (exceptions: treated solid malignancy in >5 years'
remission, treated basal or squamous cell carcinomas of the skin).
16. History of concomitant genetic syndrome associated with bone marrow failure such as
Fanconi anemia, Kostmann syndrome, or Shwachman-Diamond syndrome