CRISPR (HPK1) Edited CD19-specific CAR-T Cells (XYF19 CAR-T Cells) for CD19+ Leukemia or Lymphoma.

July 27, 2019 updated by: Gao Guangxun, Xijing Hospital

A Safety Study of Autologous T Cells Engineered to Target CD19 and CRISPR Gene Edited to Eliminate Endogenous HPK1 (XYF19 CAR-T Cells) for Relapsed or Refractory Haematopoietic Malignancies.

This is a first-in-human trial proposed to test CD19-specific CAR-T cells with edited endogenous HPK1 (XYF19 CAR-T cells) in patients with relapsed or refractory CD19+ leukemia or lymphoma. This is an investigational study designed as a single-center, open-label and single-arm clinical trial.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Shannxi
      • Xi'an, Shannxi, China, 710032

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Subject must meet all the following criteria to be selected:

    1. Willing to provide consent/assent for participation in the study by patient or his/her legal guardian;
    2. Male or Female subjects age ≥18 and ≤55 years;
    3. Evidence of relapsed/refractory CD19+ B cell hematological malignancies. The most common relapsed/refractory B cell hematological malignancies include: (1) B cell acute lymphoblastic leukemia (B-ALL); (2) B cell lymphomas, including indolent B cell lymphoma (CLL, FL, MZL, LPL, HCL) and aggressive B cell lymphoma (DLBCL, BL, MCL)；

    4. Subjects (20 subjects of B cell acute lymphoblastic leukemia and 20 subjects of B cell lymphoma) with the following conditions:

      1. Failure to achieve complete remission (CR) after at least two lines of standard chemotherapy while not suitable for HSCT (auto/allo-HSCT)；
      2. Relapse after CR, but not eligible for HSCT (auto/allo-HSCT);
      3. Failure to achieve remission or relapse after HSCT;
    5. Leukemia patient confirmed by bone marrow aspiration that has not been alleviated; lymphoma patient with measurable or assessable lesions;

    6. Adequate organ function:

      1. Liver: ALT/AST ≥ 3 × ULN, total bilirubin ≤34.2 mol/L;
      2. Kidney: Creatinine<220 µmol/L, creatinine clearance rate (CCR) ≥ 60 mL/min;
      3. Lung: arterial oxygen saturation ≥95%;
      4. Heart: Left ventricular ejection fraction (LVEF) ≥40%;
      5. Absolute lymphocyte count (ALC) ≥ 100/μL, absolute neutrophil count (ANC) ≥ 1,000/μL, platelets (PLT) ≥ 75,000/μL;
    7. No prior anti-cancer therapy, including chemotherapy, radiotherapy, immunotherapy (immunosuppression) within 4 weeks prior to enrollment, and toxic reactions of all prior treatments recovered to grade ≤1 at the time of enrollment (except for low toxicity such as alopecia);
    8. Presence of smooth peripheral superficial venous blood flow to fulfill intravenous infusion;
    9. Karnofsky performance score ≥60; ECOG ≤2; estimated survival ≥3 months.

Exclusion Criteria:

  • Subjects meeting one or more of the following criteria will be excluded:

    1. Female patient who is pregnant or breastfeeding ;
    2. Male or Female patient within Pregnancy Program in 1 year;
    3. Unwilling or unable to guarantee effective contraceptive measures (condoms or contraceptives) within 1 year after enrollment;
    4. Presence of uncontrolled infectious disease within 4 weeks prior to enrollment:
    5. Active hepatitis B or hepatitis C infection;
    6. HIV infection;
    7. Active TB;
    8. Presence of active malignancy other than disease under study, confirmed by pathology;
    9. Severe autoimmune diseases or immunodeficiency;
    10. Suffering from allergies;
    11. Joining another clinical trial within 6 weeks prior to enrollment;
    12. Using systemic corticosteroid within 4 weeks prior to enrollment (except for those who use inhaled steroids);
    13. Psychiatric disorders;
    14. History of epilepsy and seizures or other CNS pathology;
    15. Addiction to or abuse of drugs;
    16. Presence of any condition that, in the opinion of the investigator, would prohibit the patient from undergoing treatment under this protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: XYF19 CAR-T cell
One arm study consisting of "3 + 3" dose escalation study design followed by dose expansion phase at determined MTD.
Genetic: XYF19 CAR-T cell
Autologous T cells engineered to specify CD19 transduced with a lentiviral vector and electroporated with CRISPR guide RNA to disrupt expression of endogenous HPK1 administered by IV injection.
Drug: Cyclophosphamide
A cytotoxic chemotherapy agent used for lymphodepletion prior to XYF19 CAR-T cells.
Drug: Fludarabine
A chemotherapy agent used for lymphodepletion prior to XYF19 CAR-T cells.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The adverse events associated with XYF19 CAR-T cells product will be assessed.
Time Frame: 30 days
Determine safety profile of a single infusion of XYF19 CAR-T cells by monitoring the frequency and severity of adverse events assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). Occurrence of study related adverse events defined as NCI CTCAE v5.0 > grade 3 possibly, probably, or definitely related to study treatment. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to adverse event.
30 days
Maximum tolerated dose (MTD) as determined by dose limiting toxicity (DLT).
Time Frame: 30 days
The MTD is defined as the dose level at which fewer than 33% of patients experience a dose limiting toxicity (DLT). The dose limiting toxicity is defined as CTCAE grades non-reversible grade 3, or any grade 4-5 allergic reactions related to the study cell infusion; CTCAE grades non-reversible grade 3, or any grade 4-5 autoimmune reactions related to the study cell infusion; or CTCAE grades non-reversible non-hematologic grade 3, or any grade 4-5 organ toxicity (cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary, or neurologic) not pre-existing or due to the underlying malignancy and occurring within 30 days of study product infusion related to study cell infusion. The study will employ a standard 3+3 design to find the MTD of XYF19 CAR-T cells dose.
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xijing Hospital

Collaborators

Xi'An Yufan Biotechnology Co.,Ltd

Investigators

  • Principal Investigator: Guangxun GAO, Dr., Xijing Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

August 1, 2019

Primary Completion (Anticipated)

August 1, 2021

Study Completion (Anticipated)

August 1, 2024

Study Registration Dates

First Submitted

July 11, 2019

First Submitted That Met QC Criteria

July 27, 2019

First Posted (Actual)

July 30, 2019

Study Record Updates

Last Update Posted (Actual)

July 30, 2019

Last Update Submitted That Met QC Criteria

July 27, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • V2.1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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