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

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.

Study Overview

• Status: Completed
• Conditions: B Cell Lymphoma; B Cell Leukemia
• Intervention / Treatment: Biological: Autologous 3rd generation CD19-targeting CAR T cells

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Uppsala, Sweden, 75185
    • Uppsala University Hospital, Dept of Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CAR T cells; Autologous 3rd generation CD19-targeting CAR T cells	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Uppsala University
• Collaborators: Karolinska University Hospital; Uppsala University Hospital; AFA Insurance; Swedish Cancer Society
• Investigators: Study Director: Angelica Loskog, PhD, Uppsala University; Principal Investigator: Gunilla Enblad, MD, PhD, Uppsala University Hospital; Principal Investigator: Hans Hagberg, MD, PhD, Uppsala University Hospital

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): May 31, 2017
• Study Completion (Actual): May 31, 2017

Study Registration Dates

• First Submitted: May 5, 2014
• First Submitted That Met QC Criteria: May 5, 2014
• First Posted (Estimate): May 7, 2014

Study Record Updates

• Last Update Posted (Actual): October 30, 2017
• Last Update Submitted That Met QC Criteria: October 27, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, B-Cell
• Other Study ID Numbers: 003:TCELL; 2013-001393-19 (EudraCT Number)