A Study Evaluating UCART019 in Patients With Relapsed or Refractory CD19+ Leukemia and Lymphoma

NCT03166878 | Unknown Phase 1

• 1 other identifier: CHN-PLAGH-BT-021
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

B Cell Leukemia; B Cell Lymphoma

Keywords

CAR-T; Cancer treatment; Immunotherapy; Adoptive cell therapy; Chimeric antigen receptor; Universal CAR-T

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (3)

• 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

Study Arms (1)

Treatment (UCART019)

EXPERIMENTAL

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

Interventions

UCART019 BIOLOGICAL

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

Treatment (UCART019)

Eligibility Criteria

• Age: 12 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participant
• Years to 75 Years (Infant, Child, Adult, Senior)
• Patient with relapsed or refractory CD19 positive B-cell leukemia or lymphoma
• Estimated life expectancy ≥ 12 weeks (according to investigator's judgement)
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Adequate organ function

You may not qualify if:

• 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
• Pregnant or nursing women

Sponsors & Collaborators

• Chinese PLA General Hospital: lead

Study Sites (1)

Biotherapeutic Department and Hematology Department of Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

RECRUITING

MeSH Terms

Conditions

Leukemia, B-Cell; Lymphoma, B-Cell

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Molecular & Immunological Department, Bio-therapeutic Department

Study Record Dates

• First Submitted: May 23, 2017
• First Posted: May 25, 2017
• Study Start: June 1, 2017
• Primary Completion: May 1, 2022
• Study Completion: May 1, 2022
• Last Updated: June 23, 2017

Record last verified: 2017-06

Locations

CN (1)