CD19-targeting CAR T Cells in Relapsed or Refractory CD19 Positive B-cell Malignancies
CD19-targeting CAR T Cells in Relapsed or Refractory CD19 Positive B-cell Malignancies
This is a single center, single arm, open-label phase 1 study to determine the safety and
 efficacy of autologous T cells expressing CD19 chimeric antigen receptors in adults with
 CD19+ B cell malignancies.
This is a single-center, Open Label phase I clinical trial, 9 subjects planned to be
 enrolled. The subjects will be divided into low-dose group, medium-dose group and high-dose
 group.Dose CAR+ cells/kg Low 1×105 Medium 2×106 High 6×106
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 or
 subsequent bone marrow relapse, or any bone marrow relapse after allogeneic
 stem cell transplant and must be ≥ 6 months from stem cell transplant at the
 time of infusion.

 -  Refractory was defined by not achieving an initial complete response after 2
 cycles of a standard chemotherapy regimen . Patients who were refractory to
 subsequent chemotherapy regimens after an initial remission were considered
 chemorefractory

 -  Patients with Ph+ acute lymphocytic leukemia were eligible if they are intolerant
 to or have not achieved a remission after two lines of tyrosine kinase inhibitor
 therapy, or if tyrosine kinase inhibitor therapy is contraindicated, or
 ineligible for allogeneic stem cell transplant because of:

 -  Comorbid disease

 -  Other contraindications to allogeneic stem cell transplant conditioning
 regimen

 -  Lack of suitable donor

 -  Prior hematopoietic stem cell transplant

 -  Declined allogeneichematopoietic stem cell transplant as a therapeutic
 option

 -  Relapsed or refractory non-Hodgkin's lymphoma

 -  Histopathological CD19+.

 -  No response to last line of therapy i. partial response as best response to
 most recent therapy regimen ii. partial response as best response to most
 recent therapy with duration no longer than 6 month from last dose of
 therapy

 -  Refractory post-Autologous stem cell transplant i. Disease progression or
 relapsed less than or equal to 12 months of Autologous stem cell transplant
 (must have biopsy proven recurrence in relapsed subjects) ii. If salvage
 therapy is given post-Autologous stem cell transplant, the subject must have
 had 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 is
 CD20-negative and an anthracycline containing chemotherapy regimen for
 subjects with transformed follicular lymphoma must have received prior
 chemotherapy for follicular lymphoma and subsequently have chemorefractory
 disease 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 determined
 by 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, and
 agree 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 any
 other 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 physiologic
 replacement

 -  Allogeneic cellular therapy, such as donor lymphocyte infusion within 6 weeks
 prior 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 [Cerebral
 spinal fluid containing blasts, but < 5 WBCs/microliter] patients were eligible)

 10. Any condition that investigator considered may increase the risk of the subjects or
 interfere with the trial results