Study of CD19 Specific Chimeric Antigen Receptor Positive T Cells (CAR-T) in ALL and NHL

Inclusion Criteria:

* Been diagnosed with CD19 (+) B-Acute lymphoblastic lymphoma or CD19 (+) Non-Hodgkin Lymphoma
* Having a measurable disease
* Relapsed/ refractory (at least 2 cases to the ward; in relapse after autologous transplantation in NHL) disease
* CD19 (+) expression in tumor cells by bone marrow/tissue or peripheral blood flow cytometry for relapse patients in the 3-month before the study period
* Bone marrow relapse after allogenic stem cell transplantation and at least 6 months between CAR-T (ISIKOK-19 ©) cell infusion and stem cell transplantation
* Philadelphia gene + B-ALL patient should have received second line treatment with tyrosine kinase inhibitor (TKI) or the usage of tyrosine kinase inhibitor (TKI) for the patient is contraindicated
* Patient; lack of appropriate donor, complications due to previous stem cell transplantation, or rejection of stem cell transplantation as a treatment option after consultation with a physician, or lack of allogenic stem cell transplantation due to high tumor burden.
* Lack of organ dysfunction:

  1. Maximum serum creatinine value: 1.7 mg / decilitre (male patients), 1.4 mg / decilitre (female patients)
  2. Liver function tests are within normal limits
  3. Bilirubin \<2.0 mg / decilitre
  4. Central oxygen pressure in room air \> 91% and no dyspnea
  5. Measurement of left ventricular ejection fraction ≥45% and left ventricular systolic function ≥28% by echocardiography during screening
* Expected survival is ≥ 3 months
* Performance condition: Karnofsky ≥ 50%
* Consent to oral contraceptives
* Approve treatment

Exclusion Criteria:

* Concomitant history of cardiac, hepatic, neurologic, nephrologic, psychiatric, autoimmune and additional oncological diseases affecting physiological functions
* Life expectancy \<2 months
* Hepatitis B, Hepatitis C, Human immunodeficiency virus infection
* Before CAR-T (ISIKOK-19 ©) cell infusion

  1. Systemic steroid treatments, tyrosine kinase inhibitors, hydroxyurea, short-acting cytotoxic drugs should be stopped 72 hours before.
  2. 1 week ago, vincristine, 6-mercaptopurine, 6-thioguanine, methotrexate (if \<25 mg / m\^2), cytosine arabinoside (if \<100 mg / m\^2), asparaginase and intrathecal treatments should be stopped.
  3. 2 weeks ago, salvage treatments (chemotherapy drugs other than lymphodepletion as part of the protocol, clofarabine, cytosine arabinoside (if\> 100 mg / m\^2), anthracyclines, methotrexate (if ≥25 mg / m\^2), drugs used for graft versus host disease, long-acting growth factors, vincristine, immunomodulatory drugs should be stopped.
  4. Radiotherapy taken outside the central nervous system should be stopped 2 weeks prior.
  5. Any systemic treatment with pegylated asparaginase and donor lymphocyte infusion should be stopped 4 weeks prior.
  6. Anti-t cell therapies containing T cell lysis or toxic antibodies should be stopped 8 weeks before.
  7. Radiotherapy for the central nervous system should be stopped 8 weeks ago.
  8. Less than 3 months after stem cell transplantation
  9. Below 60% in tissue biopsies and / or CD19 expression in tumor cells by flow cytometric analysis in bone marrow is below 85%
* Allergic to drugs that are used at any stage of treatment
* Having received experimental drug treatment in the last month
* Previously entered a cellular therapy and / or a gene therapy program
* Disapproval of the storage of tissues and cells
* Isolated disease that occurs outside the bone
* A genetic disease associated with concomitant bone marrow failure
* Active Grade 2-4 acute or diffuse chronic graft versus host disease
* Being pregnant or breastfeeding
* Disapproval the treatment
* Patients with slow CAR-T cell expansion (the cell number is not doubled in 48 hours) and with less than 10% expression of CAR-T cells during production, \< 60% cytotoxicity results in in-vitro study (i.e, patients whose product is inappropriate)