Leukemia Lymphocytic Acute (ALL) in RelapsePhase 1NCT04037566
CRISPR (HPK1) Edited CD19-specific CAR-T Cells (XYF19 CAR-T Cells) for CD19+ Leukemia or Lymphoma.
A Phase 1 study testing XYF19 CAR-T cell, Cyclophosphamide and Fludarabine in people with Leukemia Lymphocytic Acute (ALL) in Relapse and Leukemia Lymphocytic Acute (All) Refractory, run by Xijing Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Leukemia Lymphocytic Acute (ALL) in Relapse, Leukemia Lymphocytic Acute (All) Refractory, Lymphoma, B-Cell
- What is being tested?
- XYF19 CAR-T cell, Cyclophosphamide and Fludarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- Aug 2019to Aug 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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)；
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- 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;
- 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);
- Presence of smooth peripheral superficial venous blood flow to fulfill intravenous infusion;
- Karnofsky performance score ≥60; ECOG ≤2; estimated survival ≥3 months.
Who cannot join
- 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;
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- 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;
- Addiction to or abuse of drugs;
- Presence of any condition that, in the opinion of the investigator, would prohibit the patient from undergoing treatment under this protocol.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Xijing Hospital
Xi'an, Shannxi, 710032
Guangxun GAO, Dr., +86 29 84775203, gaoguangxun@fmmu.edu.cn
Yu WANG, Dr., +86 29 88764122, yu.wang@yufanbio.com
About this study
Official title: 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.
- Conditions
- Leukemia Lymphocytic Acute (ALL) in Relapse, Leukemia Lymphocytic Acute (All) Refractory, Lymphoma, B-Cell, CD19 Positive
- Being tested
- XYF19 CAR-T cell, Cyclophosphamide, Fludarabine
- Keywords
- Leukemia Lymphocytic Acute, Lymphoma, B-Cell
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XYF19 CAR-T cellGenetic
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.
CyclophosphamideDrug
A cytotoxic chemotherapy agent used for lymphodepletion prior to XYF19 CAR-T cells.
FludarabineDrug
A chemotherapy agent used for lymphodepletion prior to XYF19 CAR-T cells.
| Study group | Role | What they receive |
|---|---|---|
| XYF19 CAR-T cell | Experimental | One arm study consisting of "3 + 3" dose escalation study design followed by dose expansion phase at determined MTD. Receives: Genetic: XYF19 CAR-T cell; Drug: Cyclophosphamide; Drug: Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2019
- Study startAug 2019 (estimated)
- Primary completionAug 2021 (estimated)
- Study completionAug 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia Lymphocytic Acute (ALL) in RelapseStudies of the same condition, open and under way.
- More trials run by Xijing HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xijing Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Xi'An Yufan Biotechnology Co.,Ltd
- Responsible party
- Principal investigator, Gao Guangxun, Xijing Hospital
- Investigators
- Guangxun GAO, Dr., Principal investigator, Xijing Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04037566
- Sponsor's protocol ID
- V2.1
- Status last verified
- Jul 2019
- First submitted
- 11 Jul 2019
- Last updated
- 30 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT04037566
- Acronym / sponsor ID
- V2.1
- Conditions
- Leukemia Lymphocytic Acute (ALL) in Relapse, Leukemia Lymphocytic Acute (All) Refractory, Lymphoma, B-Cell, CD19 Positive
- Keywords
- Leukemia Lymphocytic Acute, Lymphoma, B-Cell
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Xijing HospitalUniversity, hospital or other
- Collaborators
- Xi'An Yufan Biotechnology Co.,Ltd
- Study start
- Aug 2019 (estimated)
- Primary completion
- Aug 2021 (estimated)
- Study completion
- Aug 2024 (estimated)
- First posted
- 30 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| XYF19 CAR-T cell | Experimental | Genetic: XYF19 CAR-T cell, Drug: Cyclophosphamide, Drug: FludarabineOne arm study consisting of "3 + 3" dose escalation study design followed by dose expansion phase at determined MTD. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (18 listed)
- Subject must meet all the following criteria to be selected:
Key exclusion criteria (17 listed)
- Subjects meeting one or more of the following criteria will be excluded:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| XYF19 CAR-T cellAutologous 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. | Genetic | XYF19 CAR-T cell |
| CyclophosphamideA cytotoxic chemotherapy agent used for lymphodepletion prior to XYF19 CAR-T cells. | Drug | XYF19 CAR-T cell |
| FludarabineA chemotherapy agent used for lymphodepletion prior to XYF19 CAR-T cells. | Drug | XYF19 CAR-T cell |
Primary outcome
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Guangxun GAO, Dr. principal investigator
Xijing Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing XYF19 CAR-T cell, Cyclophosphamide and Fludarabine in people with Leukemia Lymphocytic Acute (ALL) in Relapse and Leukemia Lymphocytic Acute (All) Refractory, run by Xijing Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Guangxun GAO, Dr. (+86 29 84775203, gaoguangxun@fmmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The adverse events associated with XYF19 CAR-T cells product will be assessed. (time frame: 30 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2019.