CD19-targeting, 3rd Generation CAR T Cells for Refractory B Cells Malignancy

Treatment of patients with B cell lymphoma or leukemia with two doses of CD19-targeting chimeric antigen receptor (CAR) T cells to evaluate for safety and efficacy. The CAR consists of a CD19 targeting antibody scFv with three intracellular signaling domains derived from CD3 zeta, CD28 and 4-1BB. Autologous T cells will be gene engineered with the CAR gene using a retrovirus vector. Prior to T cell infusion, the patients will be subjected to preconditioning treatment. After the second infusion patients will be subjected to immunomodulatory treatment. After T cell infusion, the patients will be evaluated for 24 months for adverse reactions, persistence of CAR T cells and efficacy.

Primary outcome:

• Registration of the safety profile such as inflammation, fever, pain, changes in blood pressure, pulse and other adverse events.

Weekly for the first 6 weeks, then at 3, 6, 9, 12, 15, 18, 21 and 24 months.

Secondary outcome:

Tumor response, CAR T cell persistence and immunological profile

• Determination of tumor size and the tumor marker CD19.
• Determination of the levels of circulating B cells.
• Determination of the level of CAR T cells (mRNA and cells) in blood and biopsies.
• Determination of activation markers on CAR T cells such as CD107a.
• Determination of the presence of immunological markers in blood and biopsies.

At 1 and 3 weeks then at 3, 6, 9, 12, 15, 18, 21 and 24 months.

Inclusion criteria

• Relapsed or refractory CD19+ B-cell lymphoma or leukemia with no other curative treatment option available.
• Measurable disease.
• All ages
• Performance status ECOG 0-2.
• Fertile females/males must consent to use contraceptives during participation of the trial.
• Signed informed consent.

Exclusion criteria

• Any significant medical or psychiatric illness that would prevent the patient from giving informed consent or from following the study procedures.
• Patients with primary CNS lymphoma.
• Known human immunodeficiency virus (HIV) infection.
• Active and/or severe infection (e.g. tuberculosis, sepsis and opportunistic infections, active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection.
• Other serious underlying medical conditions, which, in the Investigator's judgment, could impair the ability of the patient to perform the treatment.
• Treatment with an investigational product within 30 days prior to enrollment, or at least 5 half-lives of that drug, which is longest.
• Pregnancy
• Patients that do not consent to that tissue and blood samples are stored in a biobank
• Patients whose cells cannot be manufactured.