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

• Sponsor: Uppsala University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03068416
• Collaborator: Uppsala University Hospital (Other), AFA Insurance (Industry)
• Enrollment: 24
• Location: 1
• Arm: 1
• Actual Duration (Months): 47
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
B-cell Leukemia; B-Cell Lymphoma	Biological: CAR T cells	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 24 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 Cells Malignancy - a Phase II Trial.
• Actual Study Start Date: Sep 18, 2017
• Actual Primary Completion Date: Aug 19, 2021
• Actual Study Completion Date: Aug 19, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Safety [24 months]

   Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Secondary Outcome Measures

1. Tumor response [24 months.]

   Determination of tumor size

2. B cell levels [24 months]

   Determination of circulating CD19+ B cells

3. CAR T cell persistence [24 months]

   Determination of the level of CAR T cells

4. Immunological profile [24 months]

   Determination of frequencies of immune cells in patient blood and tissues

5. Cytokine profile [24 months]

   Determination of cytokine profile in patient blood

Eligibility Criteria

Criteria

• Ages Eligible for Study: 0 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

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
• AFA Insurance

Investigators

• Principal Investigator: Gunilla Enblad, MD, PhD, Uppsala University Hospital, Dept of Oncology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Uppsala University
• ClinicalTrials.gov Identifier: NCT03068416
• Other Study ID Numbers: 004:TCELL; 2016-004043-36
• First Posted: Mar 1, 2017
• Last Update Posted: Oct 20, 2021
• Last Verified: Oct 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Leukemia, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell

Study Results

No Results Posted as of Oct 20, 2021