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

B-Cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03068416
• Other study ID #: 004:TCELL
• Secondary ID: 2016-004043-36
• Status: Completed
• Phase: Phase 2
• Start date: September 18, 2017
• Est. completion date: August 19, 2021

Study information

• Verified date: October 2021
• Source: Uppsala University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: August 19, 2021
• Est. primary completion date: August 19, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 100 Years

Eligibility

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.

Related Conditions & MeSH terms

• B-cell Leukemia
• B-Cell Lymphoma
• Leukemia, B-Cell
• Leukemia, Lymphocytic, Chronic, B-Cell

Intervention

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

Locations

Country	Name	City	State
Sweden	Uppsala University Hospital, Dept of Oncology	Uppsala

Sponsors (3)

Lead Sponsor	Collaborator
Uppsala University	AFA Insurance, Uppsala University Hospital

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	24 months
Secondary	Tumor response	Determination of tumor size	24 months.
Secondary	B cell levels	Determination of circulating CD19+ B cells	24 months
Secondary	CAR T cell persistence	Determination of the level of CAR T cells	24 months
Secondary	Immunological profile	Determination of frequencies of immune cells in patient blood and tissues	24 months
Secondary	Cytokine profile	Determination of cytokine profile in patient blood	24 months