CD19-targeting, 3rd Generation CAR T Cells for Refractory B Cells Malignancy

CD19-targeting, 3rd Generation CAR T Cells for Refractory B Cells Malignancy - a Phase II Trial.

Treatment of patients with B cell lymphoma or leukemia with two doses of CD19-targeting chimeric antigen receptor (CAR) T cells to evaluate for safety and efficacy.

Study Overview

• Status: Completed
• Conditions: B-Cell Lymphoma; B-cell Leukemia
• Intervention / Treatment: Biological: CAR T cells

Detailed Description

Treatment of patients with B cell lymphoma or leukemia with two doses of CD19-targeting chimeric antigen receptor (CAR) T cells to evaluate for safety and efficacy. 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 the second infusion patients will be subjected to immunomodulatory treatment. After T cell infusion, the patients will be evaluated for 24 months for adverse reactions, persistence of CAR T cells and efficacy.

Primary outcome:

- Registration of the safety profile such as inflammation, fever, pain, changes in blood pressure, pulse and other adverse events.

Weekly for the first 6 weeks, then at 3, 6, 9, 12, 15, 18, 21 and 24 months.

Secondary outcome:

Tumor response, CAR T cell persistence and immunological profile

• Determination of tumor size and the tumor marker CD19.
• Determination of the levels of circulating B cells.
• Determination of the level of CAR T cells (mRNA and cells) in blood and biopsies.
• Determination of activation markers on CAR T cells such as CD107a.
• Determination of the presence of immunological markers in blood and biopsies.

At 1 and 3 weeks then at 3, 6, 9, 12, 15, 18, 21 and 24 months.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 100 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Relapsed or refractory CD19+ B-cell lymphoma or leukemia with no other curative treatment option available.
2. Measurable disease.
3. All ages
4. Performance status ECOG 0-2.
5. Fertile females/males must consent to use contraceptives during participation of the trial.
6. Signed informed consent.

Exclusion Criteria:

1. Any significant medical or psychiatric illness that would prevent the patient from giving informed consent or from following the study procedures.
2. Patients with primary CNS lymphoma.
3. Known human immunodeficiency virus (HIV) infection.
4. Active and/or severe infection (e.g. tuberculosis, sepsis and opportunistic infections, active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection.
5. Other serious underlying medical conditions, which, in the Investigator's judgment, could impair the ability of the patient to perform the treatment.
6. Treatment with an investigational product within 30 days prior to enrollment, or at least 5 half-lives of that drug, which is longest.
7. Pregnancy
8. Patients that do not consent to that tissue and blood samples are stored in a biobank
9. Patients whose cells cannot be manufactured.

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: CAR T cells; Autologous CD19-targeting, 3rd generation CAR T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor response	Determination of tumor size	24 months.
B cell levels	Determination of circulating CD19+ B cells	24 months
CAR T cell persistence	Determination of the level of CAR T cells	24 months
Immunological profile	Determination of frequencies of immune cells in patient blood and tissues	24 months
Cytokine profile	Determination of cytokine profile in patient blood	24 months

Collaborators and Investigators

• Sponsor: Uppsala University
• Collaborators: Uppsala University Hospital; AFA Insurance
• Investigators: Principal Investigator: Gunilla Enblad, MD, PhD, Uppsala University Hospital, Dept of Oncology

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2017
• Primary Completion (Actual): August 19, 2021
• Study Completion (Actual): August 19, 2021

Study Registration Dates

• First Submitted: February 21, 2017
• First Submitted That Met QC Criteria: February 24, 2017
• First Posted (Actual): March 1, 2017

Study Record Updates

• Last Update Posted (Actual): October 20, 2021
• Last Update Submitted That Met QC Criteria: October 14, 2021
• Last Verified: October 1, 2021

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: 004:TCELL; 2016-004043-36 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No