B Cell Lymphoma Clinical Trial
Official title:
Phase I/II Study to Determine the Safety, Tolerability, Biological Activity and Efficacy of Universal CRISPR-Cas9 Gene-Editing CAR-T Cells Targeting CD19(UCART019) in Patients With Relapsed or Refractory CD19+ Leukemia and Lymphoma
Verified date | June 2017 |
Source | Chinese PLA General Hospital |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
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 |
Country | Name | City | State |
---|---|---|---|
China | Biotherapeutic Department and Hematology Department of Chinese PLA General Hospital | Beijing | Beijing |
Lead Sponsor | Collaborator |
---|---|
Chinese PLA General Hospital |
China,
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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