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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04037566
Recruitment Status : Recruiting
First Posted : July 30, 2019
Last Update Posted : July 30, 2019
Sponsor:
Collaborator:
Xi'An Yufan Biotechnology Co.,Ltd
Information provided by (Responsible Party):
Gao Guangxun, Xijing Hospital

Tracking Information
First Submitted Date  ICMJE July 11, 2019
First Posted Date  ICMJE July 30, 2019
Last Update Posted Date July 30, 2019
Estimated Study Start Date  ICMJE August 2019
Estimated Primary Completion Date August 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 27, 2019)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CRISPR (HPK1) Edited CD19-specific CAR-T Cells (XYF19 CAR-T Cells) for CD19+ Leukemia or Lymphoma.
Official Title  ICMJE 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.
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Leukemia Lymphocytic Acute (ALL) in Relapse
  • Leukemia Lymphocytic Acute (All) Refractory
  • Lymphoma, B-Cell
  • CD19 Positive
Intervention  ICMJE
  • 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.
Study Arms  ICMJE Experimental: XYF19 CAR-T cell
One arm study consisting of "3 + 3" dose escalation study design followed by dose expansion phase at determined MTD.
Interventions:
  • Genetic: XYF19 CAR-T cell
  • Drug: Cyclophosphamide
  • Drug: Fludarabine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 27, 2019)		 40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2024
Estimated Primary Completion Date August 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Guangxun GAO, Dr. +86 29 84775203 gaoguangxun@fmmu.edu.cn
Contact: Yu WANG, Dr. +86 29 88764122 yu.wang@yufanbio.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04037566
Other Study ID Numbers  ICMJE V2.1
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Gao Guangxun, Xijing Hospital
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Xijing Hospital
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Xi'An Yufan Biotechnology Co.,Ltd
Investigators  ICMJE
Principal Investigator: Guangxun GAO, Dr. Xijing Hospital
PRS Account Xijing Hospital
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP