CD19-targeting 3rd Generation CAR T Cells for Refractory B Cell Malignancy - a Phase I/IIa Trial.

B Cell Lymphoma Clinical Trial

Official title:

CD19-targeting 3rd Generation CAR T Cells for Refractory B Cell Malignancy - a Phase I/IIa Trial.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02132624
• Other study ID #: 003:TCELL
• Secondary ID: 2013-001393-19
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: May 5, 2014
• Last updated: October 27, 2017
• Start date: April 2014
• Est. completion date: May 31, 2017

Study information

• Verified date: October 2017
• Source: Uppsala University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: May 31, 2017
• Est. primary completion date: May 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• B Cell Leukemia
• B Cell Lymphoma
• Leukemia, B-Cell
• Leukemia, Lymphocytic, Chronic, B-Cell
• Lymphoma, B-Cell

Intervention

Biological:
• Autologous 3rd generation CD19-targeting CAR T cells
Autologous CD19-targeting CAR T cells with three signaling domains derived from CD3zeta, CD28 and 4-1BB.

Locations

Country	Name	City	State
Sweden	Uppsala University Hospital, Dept of Oncology	Uppsala

Sponsors (5)

Lead Sponsor	Collaborator
Uppsala University	AFA Försäkring AB, Sweden, Karolinska University Hospital, Swedish Cancer Society, Uppsala University Hospital

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	B cell number and immunoglobulins	Number of blood B cells and immunoglobulins will be evaluated by routine diagnostics	Weekly for 5 weeks, then every 3 months post treatment up to 24 months
Primary	CAR T cell persistence	Presence of circulating CAR T cells will be evaluated with flow cytometry and real time PCR in patient blood.	At week 1 and 5, there after every 3 months post treatment up to 24 months
Secondary	Tumor load	Tumor load will be quantified with radiology, bone marrow and/or blood samples dependent on diagnosis.	Every 3 months post treatment up to 24 months