A Feasibility and Safety Study of Universal Dual Specificity CD19 and CD20 or CD22 CAR-T Cell Immunotherapy for Relapsed or Refractory Leukemia and Lymphoma

B Cell Lymphoma Clinical Trial

Official title:

Phase I/II Study to Evaluate Treatment of Relapsed or Refractory Leukemia and Lymphoma With Universal CRISPR-Cas9 Gene-Editing CAR-T Cells Targeting CD19 and CD20 or CD22

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03398967
• Other study ID #: CHN-PLAGH-BT-026
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: January 8, 2018
• Last updated: January 8, 2018
• Start date: January 2, 2018
• Est. completion date: May 20, 2022

Study information

• Verified date: January 2018
• Source: Chinese PLA General Hospital
• Contact: Wenying Zhang
• Phone: 86-10-55499341
• Email: zhangwenying.1984[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

CD19-directed CAR-T cell therapy has shown promising results for the treatment of relapsed or refractory B-cell malignancies; however, a subset of patients relapse due to the loss of CD19 in tumor cells. Dual Specificity CD19 and CD20 or CD22 CAR-T cells can recognize and kill the CD19 negative malignant cells through recognition of CD20 or CD22. This is a phase 1/2 study designed to determine the safety of the allogenic gene-edited dual specificity CD19 and CD20 or CD22 CAR-T cells and the feasibility of making enough to treat patients with relapsed or refractory hematological malignancies.

Description:

1. PRIMARY OBJECTIVES:

1. To evaluate the feasibility and safety of universal dual specificity CD19 and CD20 or CD22 CAR-T cells in patients with relapsed or refractory leukemia and lymphoma.

2. To evaluate the duration of in vivo persistence of adoptively transferred T cells, and the phenotype of persisting T cells. Real Time polymerase chain receptor (RT-PCR) and Flow cytometry(FCM) analysis of PB,BM and lymph node will be used to detect and quantify survival of universal dual specificity CD19 and CD20 or CD22 CAR-T cells over time.

2. SECONDARY OBJECTIVES:

1. For patients with detectable disease, measure anti-tumor response due to universal dual specificity CD19 and CD20 or CD22 CAR-T cell infusions.

2. Determine if cellular or humoral host immunity develops against the murine anti-CD19, and assess correlation with loss of detectable universal dual specificity CD19 and CD20 or CD22 CAR-T cells (loss of engraftment).

The CAR-T cells will be administered by i.v. injection over 20-30 minutes as a using a "split dose" approach to dosing: 10% on day 0, 30% on day 1 and 60% on day 2.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: May 20, 2022
• Est. primary completion date: May 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Male or female participant

2. 12 Years to 70 Years (Child, Adult, Senior)

3. Patient with relapsed or refractory B-cell leukemia or lymphoma

4. Estimated life expectancy = 12 weeks (according to investigator's judgement)

5. Eastern Cooperative Oncology Group (ECOG) performance status = 1

6. Adequate organ function

Exclusion Criteria:

1. Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease

2. Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification or chronic myelogenous leukemia lymphoid blast crisis

3. Richter's syndrome

4. Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of screening

5. Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy

6. Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis is allowed), Prophylactic antibiotic, antiviral and antifungal treatment is permissible

7. Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening

8. Patient has an investigational medicinal product within the last 30 days prior to screening

9. Previous treatment with investigational gene or cell therapy medicine products

10. Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary

11. Pregnant or nursing women

Related Conditions & MeSH terms

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

Intervention

Biological:
• Universal Dual Specificity CD19 and CD20 or CD22 CAR-T Cells
Biological: Universal Dual Specificity CD19 and CD20 or CD22 CAR-T Cells Day 0: 10% of total dose Day 1: 30% of total dose if patient is stable (no significant toxicity) from prior dose. D2: 60% of total dose if patient is stable (no significant toxicity) from prior dose Other: Laboratory Biomarker Analysis

Locations

Country	Name	City	State
China	Biotherapeutic Department and Hematology Department of Chinese PLA General Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Chinese PLA General Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability		24 weeks
Primary	MTD of universal dual specificity CD19 and CD20 or CD22 CAR-T cells	The highest dose of universal dual specificity CD19 and CD20 or CD22 CAR-T cells that is estimated to result in defined Dose Limiting Toxicity (DLT) with the exception of allowable 'expected' AEs associated with the intravenous infusion of universal dual s	4 weeks
Primary	Copies numbers of CAR in peripheral blood(PB), bone marrow(BM)and lymph nodes		24 weeks
Secondary	Six-month Objective response rate of complete remission and partial remission		24 weeks
Secondary	Six-month Overall survival		24 weeks
Secondary	Six-month Progression free survival		24 weeks