B Cell Leukemia, B Cell Lymphoma
Conditions
Brief summary
Chimeric antigen receptor (CAR) T cells targeting CD19 will be evaluated for safety and efficacy in patients with B cell lymphoma or leukemia. 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 T cell infusion, the patients will be evaluated for 24 months for adverse reactions, persistence of CAR T cells and efficacy.
Interventions
BIOLOGICALAutologous 3rd generation CD19-targeting CAR T cells
Autologous CD19-targeting CAR T cells with three signaling domains derived from CD3zeta, CD28 and 4-1BB.
Sponsors
Uppsala University
Uppsala University Hospital
Karolinska University Hospital
AFA Insurance
Swedish Cancer Society
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Relapsed or refractory CD19+ B-cell lymphoma or leukemia. * Measurable disease. * Performance status ECOG 0-2. * \>18 years old. * 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. * Treatment with an investigational product within 30 days prior to enrollment, or at least 5 half lives of that drug, which is longest. * Patients that do not consent to that tissue and blood samples are stored in a biobank. * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CAR T cell persistence | At week 1 and 5, there after every 3 months post treatment up to 24 months | Presence of circulating CAR T cells will be evaluated with flow cytometry and real time PCR in patient blood. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tumor load | Every 3 months post treatment up to 24 months | Tumor load will be quantified with radiology, bone marrow and/or blood samples dependent on diagnosis. |
Other
| Measure | Time frame | Description |
|---|---|---|
| B cell number and immunoglobulins | Weekly for 5 weeks, then every 3 months post treatment up to 24 months | Number of blood B cells and immunoglobulins will be evaluated by routine diagnostics |
Countries
Sweden
Outcome results
None listed