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

• ClinicalTrials.gov Identifier: NCT02132624
• Recruitment Status: Completed
• First Posted: May 7, 2014
• Last Update Posted: October 30, 2017
• Sponsor: Uppsala University
• Collaborators: Uppsala University Hospital; Karolinska University Hospital; AFA Insurance; Swedish Cancer Society
• Information provided by (Responsible Party): Uppsala University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
B Cell Lymphoma; B Cell Leukemia	Biological: Autologous 3rd generation CD19-targeting CAR T cells	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: CD19-targeting 3rd Generation CAR T Cells for Refractory B Cell Malignancy - a Phase I/IIa Trial.
• Study Start Date: April 2014
• Actual Primary Completion Date: May 31, 2017
• Actual Study Completion Date: May 31, 2017

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. CAR T cell persistence [ Time Frame: 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 Outcome Measures :

1. Tumor load [ Time Frame: 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 Outcome Measures:

1. B cell number and immunoglobulins [ Time Frame: 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Sweden

Uppsala University Hospital, Dept of Oncology

Uppsala, Sweden, 75185

Sponsors and Collaborators

Uppsala University

Uppsala University Hospital

Karolinska 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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Uppsala University
• ClinicalTrials.gov Identifier: NCT02132624
• Other Study ID Numbers: 003:TCELL; 2013-001393-19 ( EudraCT Number )
• First Posted: May 7, 2014
• Last Update Posted: October 30, 2017
• Last Verified: October 2017

Additional relevant MeSH terms:

Leukemia, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Neoplasms; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia