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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

Primary Purpose

B Cell Leukemia, B Cell Lymphoma

Status

Unknown status

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

Universal Dual Specificity CD19 and CD20 or CD22 CAR-T Cells

About this trial

This is an interventional treatment trial for B Cell Leukemia

Eligibility Criteria

12 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female participant
12 Years to 70 Years (Child, Adult, Senior)
Patient with relapsed or refractory B-cell leukemia or lymphoma
Estimated life expectancy ≥ 12 weeks (according to investigator's judgement)
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
Adequate organ function

Exclusion Criteria:

Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease
Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification or chronic myelogenous leukemia lymphoid blast crisis
Richter's syndrome
Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of screening
Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy
Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis is allowed), Prophylactic antibiotic, antiviral and antifungal treatment is permissible
Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening
Patient has an investigational medicinal product within the last 30 days prior to screening
Previous treatment with investigational gene or cell therapy medicine products
Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
Pregnant or nursing women

Sites / Locations

Biotherapeutic Department and Hematology Department of Chinese PLA General HospitalRecruiting

Outcomes

Primary Outcome Measures

Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability

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

Copies numbers of CAR in peripheral blood(PB), bone marrow(BM)and lymph nodes

Secondary Outcome Measures

Six-month Objective response rate of complete remission and partial remission

Six-month Overall survival

Six-month Progression free survival

Full Information

NCT ID

NCT03398967

First Posted

January 8, 2018

Last Updated

January 8, 2018

Sponsor

Chinese PLA General Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03398967

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2018

Overall Recruitment Status

Unknown status

Study Start Date

January 2, 2018 (Actual)

Primary Completion Date

May 20, 2022 (Anticipated)

Study Completion Date

May 20, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Chinese PLA General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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.

Detailed Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

B Cell Leukemia, B Cell Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

80 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type

Biological

Intervention Name(s)

Universal Dual Specificity CD19 and CD20 or CD22 CAR-T Cells

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability

Time Frame

24 weeks

Title

MTD of universal dual specificity CD19 and CD20 or CD22 CAR-T cells

Description

Time Frame

4 weeks

Title

Copies numbers of CAR in peripheral blood(PB), bone marrow(BM)and lymph nodes

Time Frame

24 weeks

Secondary Outcome Measure Information:

Title

Six-month Objective response rate of complete remission and partial remission

Time Frame

24 weeks

Title

Six-month Overall survival

Time Frame

24 weeks

Title

Six-month Progression free survival

Time Frame

24 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female participant 12 Years to 70 Years (Child, Adult, Senior) Patient with relapsed or refractory B-cell leukemia or lymphoma Estimated life expectancy ≥ 12 weeks (according to investigator's judgement) Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 Adequate organ function Exclusion Criteria: Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification or chronic myelogenous leukemia lymphoid blast crisis Richter's syndrome Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of screening Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis is allowed), Prophylactic antibiotic, antiviral and antifungal treatment is permissible Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening Patient has an investigational medicinal product within the last 30 days prior to screening Previous treatment with investigational gene or cell therapy medicine products Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary Pregnant or nursing women

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Wenying Zhang

Phone

86-10-55499341

zhangwenying.1984@163.com

Facility Information:

Facility Name

Biotherapeutic Department and Hematology Department of Chinese PLA General Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100853

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Weidong Han, Dr.

Phone

86-10-13651392893

hanwdrsw@sina.com

First Name & Middle Initial & Last Name & Degree

Daihong Liu, Dr.

Phone

86-10-55499136

daihongrm@163.com

First Name & Middle Initial & Last Name & Degree

Weidong Han, Dr.

First Name & Middle Initial & Last Name & Degree

Daihong Liu, Dr.

12. IPD Sharing Statement

Learn more about this trial

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

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