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

NCT04037566 | Unknown Phase 1

• 1 other identifier: V2.1
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Leukemia Lymphocytic Acute (ALL) in Relapse; Leukemia Lymphocytic Acute (All) Refractory; Lymphoma, B-Cell; CD19 Positive

Keywords

Leukemia Lymphocytic Acute; Lymphoma, B-Cell

Outcome Measures

Primary Outcomes (2)

• The adverse events associated with XYF19 CAR-T cells product will be assessed.

  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).

  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

Study Arms (1)

XYF19 CAR-T cell

EXPERIMENTAL

One arm study consisting of "3 + 3" dose escalation study design followed by dose expansion phase at determined MTD.

Genetic: XYF19 CAR-T cell; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

XYF19 CAR-T cell GENETIC

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.

XYF19 CAR-T cell

Cyclophosphamide DRUG

A cytotoxic chemotherapy agent used for lymphodepletion prior to XYF19 CAR-T cells.

XYF19 CAR-T cell

Fludarabine DRUG

A chemotherapy agent used for lymphodepletion prior to XYF19 CAR-T cells.

XYF19 CAR-T cell

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subject must meet all the following criteria to be selected:
• Willing to provide consent/assent for participation in the study by patient or his/her legal guardian;
• Male or Female subjects age ≥18 and ≤55 years;
• 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)；
• Subjects (20 subjects of B cell acute lymphoblastic leukemia and 20 subjects of B cell lymphoma) with the following conditions:
• Failure to achieve complete remission (CR) after at least two lines of standard chemotherapy while not suitable for HSCT (auto/allo-HSCT)；
• Relapse after CR, but not eligible for HSCT (auto/allo-HSCT);
• Failure to achieve remission or relapse after HSCT;
• Leukemia patient confirmed by bone marrow aspiration that has not been alleviated; lymphoma patient with measurable or assessable lesions;
• Adequate organ function:
• Liver: ALT/AST ≥ 3 × ULN, total bilirubin ≤34.2 mol/L;
• Kidney: Creatinine\<220 µmol/L, creatinine clearance rate (CCR) ≥ 60 mL/min;
• Lung: arterial oxygen saturation ≥95%;
• Heart: Left ventricular ejection fraction (LVEF) ≥40%;
• Absolute lymphocyte count (ALC) ≥ 100/μL, absolute neutrophil count (ANC) ≥ 1,000/μL, platelets (PLT) ≥ 75,000/μL;

You may not qualify if:

• Subjects meeting one or more of the following criteria will be excluded:
• Female patient who is pregnant or breastfeeding ;
• Male or Female patient within Pregnancy Program in 1 year;
• Unwilling or unable to guarantee effective contraceptive measures (condoms or contraceptives) within 1 year after enrollment;
• Presence of uncontrolled infectious disease within 4 weeks prior to enrollment:
• Active hepatitis B or hepatitis C infection;
• HIV infection;
• Active TB;
• Presence of active malignancy other than disease under study, confirmed by pathology;
• Severe autoimmune diseases or immunodeficiency;
• Suffering from allergies;
• Joining another clinical trial within 6 weeks prior to enrollment;
• Using systemic corticosteroid within 4 weeks prior to enrollment (except for those who use inhaled steroids);
• Psychiatric disorders;
• History of epilepsy and seizures or other CNS pathology;

Sponsors & Collaborators

• Xijing Hospital: lead
• Xi'An Yufan Biotechnology Co.,Ltd: collaborator

Study Sites (1)

Xijing Hospital

Xi'an, Shannxi, 710032, China

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, B-Cell

Interventions

Cyclophosphamide; fludarabine

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Guangxun GAO, Dr.

  Xijing Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guangxun GAO, Dr.

CONTACT

+86 29 84775203; gaoguangxun@fmmu.edu.cn

Yu WANG, Dr.

CONTACT

+86 29 88764122; yu.wang@yufanbio.com

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 Hematology Department

Study Record Dates

• First Submitted: July 11, 2019
• First Posted: July 30, 2019
• Study Start: August 1, 2019
• Primary Completion: August 1, 2021
• Study Completion: August 1, 2024
• Last Updated: July 30, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)