XLCART001 Treatment in Relapsed/Refractory/High-risk B-cell Malignancy Subjects

A Single-center, Open Study Evaluating Efficacy and Safety of XLCART001（CD-19） Treatment in Relapsed/Refractory/High-risk B-cell Malignancy Subjects

The trial is a single arm, single-center, non-randomized clinical trial which is designed to evaluate the efficacy and safety of XLCART001 in treatment of relapsed/refractory/high-risk B-cell malignancy subjects

Study Overview

• Status: Unknown
• Conditions: Lymphoma, B-Cell; Leukemia, B-cell
• Intervention / Treatment: Biological: chimeric antigen receptor T cells

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjin, Jiangsu, China, 210029
      • Department of Haematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥18 years, male and female,
• Confirmed as CD19-positive B cell lymphoma/leukemia by immunohistochemistry or flow cytometry
• No effective treatment
• Patients must have a measurable or evaluable disease at the time of enrollment.

• Adequate organ system function including:

  • ALT/AST < 3 upper limit of normal; Total Bilirubin < 2.5 upper limit of normal
  • Creatinine < 2 upper limit of normal
  • Oxygen saturation ≥ 95%
  • Left ventricular ejection fraction ≥ 40%
  • Number of neutrophil ≥ 0.75×10^9/L, number of platelet ≥ 50×10^9/L
• At least 4 weeks from receiving previous treatment (radiotherapy, chemotherapy, monoclonal antibody therapy or other treatments)
• No contraindications of peripheral blood apheresis
• Female subjects in childbearing age, their serum or urine pregnancy test must be negative. All patients must agree to take effective contraceptive measures during the trial measures
• ECOG score 0-2, expected survival ≥ 12 weeks

Exclusion Criteria:

• Women who are pregnant or lactating. Patients have breeding intent in 12 months or cannot take effective contraceptive measures during the trial measures
• Uncontrollable active infection within four week. Prophylactic antibiotic, antiviral and antifungal treatment is permissible. Active hepatitis B or hepatitis C virus infection, as well as acquired, congenital immune deficiency diseases, including but not limited to HIV-infected persons
• Subjects with any autoimmune disease or any immune deficiency disease
• Have a history of allergy to antibodies or cellular products
• Participated in any other clinical trial within four weeks
• Used of systemic steroids within four weeks (using inhaled steroids or ≤ 20mg/d prednison are exceptions)
• Have mental diseases
• Have history of drug addiction
• The investigators believe that any increase in the risk of the subject or interference with the results of the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	Overall response rate (ORR) = complete response (CR) rate + partial response (PR) rate, ORR will be assessed at weeks 12.	12 weeks
Overall Survival	from the time of enrollment to death from any cause or the date of the last follow-up visit	6 months,1 year, 2 years
Progression-free Survival	the time from enrollment to disease progression, death from any cause, or the date of the last follow-up visit	12 weeks,6 months,1 year, 2 years
Event-free Survival	the time from enrollment to any events, or the date of the last follow-up visit	12 weeks,6 months,1 year, 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity (DLT)	Non-haematological dose-limiting toxicities was any toxicity of grade 3 or higher occurring within 28 days of XLCART001 infusion judged possibly related to the treatment regimen.The following toxicities were not considered dose limiting toxicities: tumor lysis syndrome, abnormal electrolytes responding to supplementation, hypoalbuminemia, liver dysfunction resolving to ≤grade 2 within 14 days, transient (<72 hours) grade 4 hepatic enzyme abnormality, and grade 3 or 4 fever or neutropenic fever.	28 days
Number of CAR-T cells	The number of CAR-T cells detected by flow cytometry and copy number of CAR-T cells tested by polymerase chain reaction	Day 1, Day 4, Day 7, Day 10, Day 14, Day 21, Day 28, 8 weeks, 12 weeks, 6 months, 1 years, 2 years
Duration of CAR-T cells	The duration of CAR-T cells detected by flow cytometry and copy number of CAR-T cells tested by polymerase chain reaction	Day 1, Day 4, Day 7, Day 10, Day 14, Day 21, Day 28, 8 weeks, 12 weeks, 6 months, 1 years, 2 years

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University

Publications and helpful links

General Publications

• Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9:CD013365. doi: 10.1002/14651858.CD013365.pub2. Review.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Anticipated): December 30, 2019
• Study Completion (Anticipated): July 1, 2020

Study Registration Dates

• First Submitted: June 27, 2018
• First Submitted That Met QC Criteria: July 14, 2018
• First Posted (Actual): July 26, 2018

Study Record Updates

• Last Update Posted (Actual): August 7, 2019
• Last Update Submitted That Met QC Criteria: August 5, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Leukemia, Lymphoid; Leukemia; Lymphoma; Lymphoma, B-Cell; Leukemia, B-Cell
• Other Study ID Numbers: JSPH-CART001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No