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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03166878
Other study ID # CHN-PLAGH-BT-021
Secondary ID
Status Recruiting
Phase Phase 1/Phase 2
First received May 23, 2017
Last updated June 22, 2017
Start date June 2017
Est. completion date May 2022

Study information

Verified date June 2017
Source Chinese PLA General Hospital
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Autologous T cells engineered to express chimeric antigen receptors (CARs) against leukemia antigens such as CD19 on B cells have shown promising results for the treatment of relapsed or refractory B-cell malignancies. However, a subset of cancer patients especially heavily pretreated cancer patients could be unable to receive this highly active therapy because of failed expansion. Moreover, it is still a challenge to manufacture an effective therapeutic product for infant cancer patients due to their small blood volume. On the other hand, the inherent characters of autologous CAR-T cell therapy including personalized autologous T cell manufacturing and widely "distributed" approach result in the difficulty of industrialization of autologous CAR-T cell therapy. Universal CD19-specific CAR-T cell(UCART019),derived from one or more healthy unrelated donors but could avoid graft-versus-host-disease (GVHD) and minimize their immunogenicity, is undoubtedly an alternative option to address above-mentioned issues. We have generated gene-disrupted allogeneic CD19-directed BBζ CAR-T cells (termed UCART019) by combining the lentiviral delivery of CAR and CRISPR RNA electroporation to disrupt endogenous TCR and B2M genes simultaneously and will test whether it can evade host-mediated immunity and deliver antileukemic effects without GVHD.

The main goal of the phase 1 portion of this phase 1/2 trial is to evaluate the safety and tolerability of several doses of UCART019 in patients with relapsed or refractory CD19+ leukemia and lymphoma, so as to establish the recommended dose and/or schedule of UCART019 for phase 2 portion. The recommended Phase 2 dose will be defined as the highest dose level of UCART019 that induced DLT in fewer than 33% of patients (i.e., one dose level below that which induced DLT in at least two of six patients). Phase 2 portion of the trial will not be initiated until the recommended Phase 2 dose is determined. In the phase 2 portion of this trial, we will mainly determine if UCART019 help the body's immune system eliminate malignant B-cells. Safety of UCART019 and impact of this treatment on survival will also be observed.


Description:

PRIMARY OBJECTIVES:

1. To evaluate the feasibility and safety of UCART019 in patients with relapsed or refractory CD19+ 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) analysis of peripheral blood(PB), bone marrow(BM) and lymph node will be used to detect and quantify survival of UCART019 over time.

SECONDARY OBJECTIVES:

1. For patients with detectable disease, measure anti-tumor response due to UCART019 cell infusions.

2. Determine if cellular or humoral host immunity develops against the murine anti-CD19, and assess correlation with loss of detectable UCART019 (loss of engraftment).

OUTLINE: This is a phase I, dose-escalation study of allogeneic CD19 CAR-T-cells followed by a phase II study.

The UCART019 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 2022
Est. primary completion date May 2022
Accepts healthy volunteers No
Gender All
Age group 12 Years to 75 Years
Eligibility Inclusion Criteria:

1. Male or female participant

2. 12 Years to 75 Years (Infant, Child, Adult, Senior)

3. Patient with relapsed or refractory CD19 positive B-cell leukemia or lymphoma

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

5. Eastern Cooperative Oncology Group (ECOG) performance status = 2

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

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
UCART019
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

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 Highest dose of UCART019 that is estimated to result in defined DLT with the exception of allowable UCART019 infusion related 'expected' AEs, using CTCAE 4.0, in less than 1/3 patients 8 weeks
Primary Copy numbers of UCAR019 in PB, BM and lymph nodes 24 weeks
Secondary Objective response rate of complete remission and partial remission.Descriptive statistics will be used 24 weeks
Secondary Overall survival.Descriptive statistics will be used 24 weeks
Secondary Progression free survival.Descriptive statistics will be used 24 weeks
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