1. Signed informed consent form must be obtained prior to any study procedure. Labs, marrows or other procedures obtained during routine clinical care may be used for eligibility if obtained within the protocol required windows.
2. Relapsed or refractory B-cell ALL/lymphoblastic lymphoma:
1. 2nd or greater relapse (marrow or CNS) OR
2. Any relapse after allogeneic hematopoietic stem cell (SCT) transplant and ≥ 6 months from stem cell transplantation at infusion OR
3. Any relapse after CAR-modified T cell therapy OR
4. Refractory disease defined as having not achieved an MRD-negative CR after > 2 chemotherapy regimens/cycles (1 cycle for relapsed patients) OR
5. Patients with Ph+ ALL are eligible if they are intolerant to or have failed tyrosine kinase inhibitor therapy OR
6. Ineligible for allogeneic SCT because of:
- Comorbid disease
- Other contraindications to allogeneic SCT conditioning regimen
- Lack of suitable donor
- Prior SCT
- Declines allogeneic SCT as the therapeutic option after documented discussion, with expected outcomes, about the role of SCT with a bone marrow transplant (BMT) physician not part of the study team
7. Patients with CNS3 disease will be eligible if CNS disease is responsive to therapy (at infusion, must meet criteria in Section 5.3)
3. Documentation of CD19 tumor expression in bone marrow or peripheral blood by flow cytometry at relapse (or a recent marrow in the case of refractory disease). If the patient has received CD19-directed therapy (i.e. blinatumomab), then the marrow should be obtained after this therapy to show CD19 expression.
4. Adequate organ function defined as:
1. A serum creatinine based on age/gender as follows:
Maximum Serum Creatinine (mg/dL)
Age Male Female
- 1 to < 2 years 0.6 0.6
- 2 to < 6 years 0.8 0.8
- 6 to < 10 years 1.0 1.0
- 10 to < 13 years 1.2 1.2
- 13 to < 16 years 1.5 1.4
- ≥ 16 years 1.7 1.4
2. ALT< 500 U/L
3. Bilirubin <2.0 mg/dl
4. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea, pulse oximetry > 92% on room air; DLCO > 40% (corrected for anemia) if PFTs are clinically appropriate as determined by the treating investigator
5. Left Ventricular Shortening Fraction (LVSF) ≥ 28% or Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO, or adequate ventricular function documented by a scan or a cardiologist.
5. Evidence of disease by standard morphologic or MRD criteria. A clinical marrow showing disease may be performed at enrollment or within 12 weeks of enrollment.
6. Age 1-24 years.
7. Adequate performance status (Lansky or Karnofsky score ≥50).
8. Subjects of reproductive potential must agree to use acceptable birth control methods, as described in protocol Section 4.3.
1. Active hepatitis B or active hepatitis C.
2. HIV Infection.
3. Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy.
4. Concurrent use of systemic steroids or immunosuppressant medications. Recent or current use of inhaled steroids or physiologic replacement with hydrocortisone is not exclusionary. For additional details regarding the use of steroids and immunosuppressant medication, please see Section 5.6.
5. CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
6. Pregnant or nursing (lactating) women.
7. Receipt of a prior investigational study agent within 4 weeks prior to screening visit.
- Note- patients who have received anti-CD19 CART cells on a study where cell infusion occurred greater than 4 weeks before the screening visit are NOT excluded.
|Maximum Eligible Age:||24 Years|
|Minimum Eligible Age:||1 Year|