Clinical trial NCT02132624: CD19-targeting 3rd Generation CAR T Cells for Refractory B Cell Malignancy - a Phase I/IIa Trial.
Official title: CD19-targeting 3rd Generation CAR T Cells for Refractory B Cell Malignancy - a Phase I/IIa Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: B Cell Lymphoma
B Cell Leukemia
Lead sponsor: Uppsala University
Sponsor class: OTHER
Collaborators: name: Uppsala University Hospital
name: Karolinska University Hospital
name: AFA Insurance
name: Swedish Cancer Society
First posted: 2014-05-07
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: CAR T cell persistence
timeFrame: At week 1 and 5, there after every 3 months post treatment up to 24 months
Secondary outcomes:
measure: Tumor load
timeFrame: Every 3 months post treatment up to 24 months
Other outcomes:
measure: B cell number and immunoglobulins
timeFrame: Weekly for 5 weeks, then every 3 months post treatment up to 24 months
Locations:
city: Uppsala
country: Sweden
facility: Uppsala University Hospital, Dept of Oncology
Study officials:
affiliation: Uppsala University
name: Angelica Loskog, PhD
role: STUDY_DIRECTOR
affiliation: Uppsala University Hospital
name: Gunilla Enblad, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Uppsala University Hospital
name: Hans Hagberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
citation: Enblad G, Karlsson H, Gammelgard G, Wenthe J, Lovgren T, Amini RM, Wikstrom KI, Essand M, Savoldo B, Hallbook H, Hoglund M, Dotti G, Brenner MK, Hagberg H, Loskog A. A Phase I/IIa Trial Using CD19-Targeted Third-Generation CAR T Cells for Lymphoma and Leukemia. Clin Cancer Res. 2018 Dec 15;24(24):6185-6194. doi: 10.1158/1078-0432.CCR-18-0426. Epub 2018 Aug 10.