A Study Evaluating UCART019 in Patients With Relapsed or Refractory CD19+ Leukemia and Lymphoma
Study Details
Study Description
Brief 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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
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To evaluate the feasibility and safety of UCART019 in patients with relapsed or refractory CD19+ leukemia and lymphoma.
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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:
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For patients with detectable disease, measure anti-tumor response due to UCART019 cell infusions.
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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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Treatment (UCART019) The UCART019 will be administered by i.v. injection over 20-30 minutes as a using a "split dose" approach to dosing: 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 |
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
|
Outcome Measures
Primary Outcome Measures
- Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability [24 weeks]
- 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]
- Copy numbers of UCAR019 in PB, BM and lymph nodes [24 weeks]
Secondary Outcome Measures
- Objective response rate of complete remission and partial remission.Descriptive statistics will be used [24 weeks]
- Overall survival.Descriptive statistics will be used [24 weeks]
- Progression free survival.Descriptive statistics will be used [24 weeks]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male or female participant
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12 Years to 75 Years (Infant, Child, Adult, Senior)
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Patient with relapsed or refractory CD19 positive B-cell leukemia or lymphoma
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Estimated life expectancy ≥ 12 weeks (according to investigator's judgement)
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Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
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Adequate organ function
Exclusion Criteria:
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Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease
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Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification or chronic myelogenous leukemia lymphoid blast crisis
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Richter's syndrome
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Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of screening
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Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy
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Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis is allowed), Prophylactic antibiotic, antiviral and antifungal treatment is permissible
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Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening
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Patient has an investigational medicinal product within the last 30 days prior to screening
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Previous treatment with investigational gene or cell therapy medicine products
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Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary
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Pregnant or nursing women
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Biotherapeutic Department and Hematology Department of Chinese PLA General Hospital | Beijing | Beijing | China | 100853 |
Sponsors and Collaborators
- Chinese PLA General Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CHN-PLAGH-BT-021