CD19-targeting CAR T Cells in Relapsed or Refractory CD19 Positive B-cell Malignancies

Inclusion Criteria:

1. CD19+ relapsed or refractory B cell malignancies:

• Relapsed or refractory B acute lymphocytic leukemia.
• Relapse was defined as presence of > 5% blasts at screening, or second orsubsequent bone marrow relapse, or any bone marrow relapse after allogeneicstem cell transplant and must be ≥ 6 months from stem cell transplant at thetime of infusion.
• Refractory was defined by not achieving an initial complete response after 2cycles of a standard chemotherapy regimen . Patients who were refractory tosubsequent chemotherapy regimens after an initial remission were consideredchemorefractory
• Patients with Ph+ acute lymphocytic leukemia were eligible if they are intolerantto or have not achieved a remission after two lines of tyrosine kinase inhibitortherapy, or if tyrosine kinase inhibitor therapy is contraindicated, orineligible for allogeneic stem cell transplant because of:
• Comorbid disease
• Other contraindications to allogeneic stem cell transplant conditioningregimen
• Lack of suitable donor
• Prior hematopoietic stem cell transplant
• Declined allogeneichematopoietic stem cell transplant as a therapeuticoption
• Relapsed or refractory non-Hodgkin's lymphoma
• Histopathological CD19+.
• No response to last line of therapy i. partial response as best response tomost recent therapy regimen ii. partial response as best response to mostrecent therapy with duration no longer than 6 month from last dose oftherapy
• Refractory post-Autologous stem cell transplant i. Disease progression orrelapsed less than or equal to 12 months of Autologous stem cell transplant (must have biopsy proven recurrence in relapsed subjects) ii. If salvagetherapy is given post-Autologous stem cell transplant, the subject must havehad no response to or relapsed after the last line of therapy
• Subjects must have received adequate prior therapy including at a minimum:anti-CD20 monoclonal antibody unless investigator determines that tumor isCD20-negative and an anthracycline containing chemotherapy regimen forsubjects with transformed follicular lymphoma must have received priorchemotherapy for follicular lymphoma and subsequently have chemorefractorydisease after transformation to Diffuse large B-cell lymphoma
• At least one measurable lesion per revised IWG Response Criteria

2. 18-75 years old
3. Expected survival ≥ 12 weeks
4. Adequate renal, hepatic, pulmonary and cardiac function defined as:

• Creatinine clearance (as estimated by Cockcroft Gault) > 60 mL/min
• Serum ALT/AST <2.5 ULN
• Total bilirubin <1.5 mg/dl, except in subjects with Gilbert's syndrome
• Cardiac ejection fraction >50%, no evidence of pericardial effusion as determinedby an echocardiogram, and no clinically significant pleural effusion
• Baseline oxygen saturation >92% on room air

5. Eastern cooperative oncology group (ECOG) performance status of 0 - 2
6. Pregnant or lactating women must have a negative pregnancy test before infusion, andagree to take effective contraception during the trial
7. Apheresis product received and accepted
8. Written informed consent

Exclusion Criteria:

1. Isolated extra-medullary relapse leukemia
2. Other malignancies
3. Concomitant genetic syndrome, with the exception of Down Syndrome
4. Burkitt's lymphoma/leukemia
5. Treatment with any prior gene therapy product, anti-CD19/anti-CD3 therapy, or anyother anti-CD19 therapy
6. Active hepatitis B, C, or any uncontrolled infection
7. Grade 2 to 4 Graft versus Host Disease (GVHD)
8. Medications or treatments that were to be excluded:

• Corticosteroids within 72 hours of infusion, with the exception of physiologicreplacement
• Allogeneic cellular therapy, such as donor lymphocyte infusion within 6 weeksprior to infusion
• Graft versus Host Disease therapies
• Chemotherapy stopped prior to lymphodepletion based on clearance
• central nervous system prophylaxis treatment

9. Active central nervous system disease (central nervous system 2 disease [Cerebralspinal fluid containing blasts, but < 5 WBCs/microliter] patients were eligible)
10. Any condition that investigator considered may increase the risk of the subjects orinterfere with the trial results