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

Phase 2

Completed

• Conditions: B-cell Leukemia; B-Cell Lymphoma
• Interventions: Biological: CAR T cells

• Registration Number: NCT03068416
• Lead Sponsor: Uppsala University

Brief Summary

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.

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 Timeline

• Study First Submitted: 2017-02-21
• Study First Submitted QC: 2017-02-24
• Study First Posted: 2017-03-01
• Study Start: 2017-09-18
• Primary Completion: 2021-08-19
• Study Completion: 2021-08-19
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-14
• Last Update Posted: 2021-10-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CAR T cells	CAR T cells	Autologous 3rd generation CD19-targeting CAR T cells

Primary Outcome Measures

Name	Time	Method
Safety	24 months	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Uppsala University Hospital, Dept of Oncology; 🇸🇪 Uppsala, Sweden