Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

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
18-75 years old
Expected survival ≥ 12 weeks

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

Exclusion Criteria:

Isolated extra-medullary relapse leukemia
Other malignancies
Concomitant genetic syndrome, with the exception of Down Syndrome
Burkitt's lymphoma/leukemia
Treatment with any prior gene therapy product, anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy
Active hepatitis B, C, or any uncontrolled infection
Grade 2 to 4 Graft versus Host Disease (GVHD)

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