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

• Sponsor: Uppsala University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02132624
• Collaborator: Uppsala University Hospital (Other), Karolinska University Hospital (Other), AFA Insurance (Industry), Swedish Cancer Society (Other)
• Enrollment: 15
• Location: 1
• Arm: 1
• Duration (Months): 38
• Patients Per Site Per Month: 0.4

Study Details

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
• 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: Apr 1, 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 [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 [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 [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

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Uppsala University
• ClinicalTrials.gov Identifier: NCT02132624
• Other Study ID Numbers: 003:TCELL; 2013-001393-19
• First Posted: May 7, 2014
• Last Update Posted: Oct 30, 2017
• Last Verified: Oct 1, 2017

• Additional relevant MeSH terms: Leukemia, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell

Study Results

No Results Posted as of Oct 30, 2017