The Clinical Application of Chimeric Antigen Receptor T Cells in the Treatment of CD19 Positive Recurrent Refractory B Cell-derived Hematological Malignancies

December 1, 2019 updated by: PersonGen BioTherapeutics (Suzhou) Co., Ltd.

CD19-CART Cells in the Treatment of CD19+ r/r B Cell-derived Hematological Malignancies

CD19 is expressed in most B malignant tumors, especially in the former B cells ALL. This makes CD19 a natural target of immunotherapy. In terms of safety, the lack of B cells caused by CD19 targeted therapy will not cause life-threatening side effects (of course, Ig supplementation is necessary in the long-term B cell inhibition therapy). Moreover, the number of B cells can be restored after removing anti-CD19 treatment measures (such as anti-CD19 CART cells). In addition, CD19 has been chosen as the target of B-ALL therapy for the following reasons: ① as the BCR signal "amplifier", CD19 plays a role in PAX-5-mediated tumor formation; ② by activating MYC (as the oncogene controlled by PAX-5, C-MYC plays a key role in promoting the malignant proliferation of B cells), CD19 can cause B-ALL formation. Based on the above reasons, CD19 has become an ideal target in the treatment of B-cell cancer.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early 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 Locations

  • China
    • Jiangsu
      • Suzhou, Jiangsu, China
        • Recruiting
        • Hematology Department of the Second Affiliated Hospital of Suzhou University

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 1. At the time of initial diagnosis, the age is 18-70 years old, regardless of gender or race
  • 2. Morphological analysis showed that the load of lymphoma was ≥ 5%
  • 3. Estimated survival time > 12 weeks
  • 4. The main investigator and the attending physician of the patient think that there is no other feasible and effective alternative treatment, such as hematopoietic stem cell transplantation
  • 5. Relapsed / refractory B-cell acute lymphocytic leukemia (all): A. objective remission rate (or) of grade 2 or higher bone marrow recurrence B. bone marrow relapse after allogeneic stem cell transplantation (SCT), SCT treatment is more than 6 months and in or state before cart-19 reinfusion C. refractory patients (CR status is not reached after 2 rounds of standard chemotherapy (CR refers to the load of myeloma detected by morphology < 5%)) D. Philadelphia chromosome positive (Ph +) and tyrosine kinase inhibitor (TKI) treatment failed twice or TKI failed to maintain or E. treatment with allogeneic SCT
  • 6. For patients with relapse, CD19 was detected in bone marrow or peripheral blood by flow cytometry within 3 months before admission
  • 7. CD19 expression on lymphoma cells: immunohistochemistry > 15% or flow cytometry > 30%
  • 8. The main organ functions are sound, including: A. renal function: radioisotope glomerular filtration rate > 60 ml / min / 1.73 m2, or serum creatinine clearance rate in line with relevant age / gender standards B. alanine transferase (ALT) < 5 times the normal maximum value of the same age C. bilirubin < 2.0 mg / dl D. to achieve the minimum pulmonary function: ≤ grade I dyspnea and indoor blood oxygen concentration > 91% E. echocardiography or multi gated angiography (MUGA) showed that the left ventricular short axis shortening rate (LVSF) was ≥ 28%, or left ventricular ejection fraction (LVEF) was ≥ 45%
  • 9. Karnofsky score (age ≥ 16 years old) ≥ 50 or zubrod-ecog-who score ≤ 2
  • 10. Sign written informed consent and obtain consent before any research is carried out
  • 11. When the above other conditions are met, the cell culture factory must receive fresh blood samples from patients. In the case of monocultured cells, they can only be accepted by the cell culture factory if the relevant tests are qualified

Exclusion Criteria:

  • 1. Recurrence of isolated extramedullary diseases
  • 2. The patient is accompanied by the following genetic syndrome: Fanconi syndrome, Kostmann syndrome, Shwachman syndrome or any known myelofailure syndrome. Patients with Down syndrome are not included in the exclusion criteria
  • 3. Patients with Burkitt's lymphoma / leukemia (i.e. patients with mature B cell all, B cell surface immunoglobulin positive (SIG +) and light chain kappa or lambda type, morphology Fab L3 or myc ectopic expression)
  • 4. Patients with previous history of malignant tumor but cured skin or cervical carcinoma in situ and patients with inactive tumor are not included in the exclusion criteria
  • 5. Previous use of gene therapy
  • 6. Previous use of anti-CD19 / CD3 combination therapy or any other anti-CD19 treatment
  • 7. Hepatitis B or C or HBV / HCV or other uncontrolled infection at the time of screening
  • 8. Screening with HIV infection
  • 9. Acute or chronic graft-versus-host reaction (GVHD) of level 2-4
  • 10. Use the following drugs: A. steroid: it is forbidden to use within 72 hours before cart-19 reinfusion, but physiological steroid treatment dose (< 6 - 12 mg / m2 / day) or equivalent hydrocortisone can be used B. allogeneic cell therapy: no donor lymphocyte infusion (DLI) is allowed within 6 weeks before cart-19 reinfusion C. GVHD treatment: any GVHD treatment (such as calmodulinase inhibitor, methotrexate, mycophenolate ester, steroid (see above), rapamycin, thalidomide or immunosuppressive antibody (such as anti-CD20 / TNF / IL6 / IL6R)) must be stopped within 4 weeks before cart-19 infusion D. chemotherapy: I. The following drugs should be stopped for at least one week before cart-19 infusion, and it is better not to accompany or follow the lymphocyte elimination chemotherapy plan: hydroxyurea, vincristine, 6-mercaptopurine, 6-thioguanine, methotrexate < 25 mg / m2, cytarabine < 10 mg / m2 / day, asparaginase; II. The following drugs should be stopped for at least four weeks before cart-19 infusion: remedial chemotherapy (such as chlorine method) Lapin, cytarabine > 100 mg / m2, anthracycline drugs, cyclophosphamide), lymphocyte clearance chemotherapy drugs are not included in the exclusion criteria E. central nervous system (CNS) disease prevention: CNS prevention and treatment should be stopped at least one week before cart-19 reinfusion (such as MTX injection into spinal cord)
  • 11. For CNS infiltration of malignant tumors, refer to the guidelines of national comprehensive cancer network (NCCN) cns-3. Note: the patients with CNS diseases who have been effectively treated are not included in the exclusion criteria. The patients cannot participate in the drug trial within 30 days before screening
  • 12. Pregnant or lactating women: 48 hours before reinfusion, the female test participants must carry out serum or urine pregnancy test, and the test result is positive
  • 13. Women of childbearing age and all men did not take effective contraceptive methods within one year after cart-19 transfusion

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: CART cells
dosage：Once dose，1.0*10^6cells/kg CART cells Administration mode:Intravenous infusion
Drug: CD19-CART
1-10x106 / kg CD19 CART cells
Other Names:
  • Targeting hcd19 chimeric antigen receptor

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
CR
Time Frame: 12 weeks after infusion of the study drug
Complete response rate (CR)
12 weeks after infusion of the study drug

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
PR
Time Frame: 12 weeks after infusion of the study drug
Partial remission rate
12 weeks after infusion of the study drug
2-year disease-free survival rate 2-year disease-free survival rate
Time Frame: 12 weeks after infusion of the study drug
2-year disease-free survival rate
12 weeks after infusion of the study drug

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
PersonGen BioTherapeutics (Suzhou) Co., Ltd.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Second Affiliated Hospital of Suzhou University

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 (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 9, 2018

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2020

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 4, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 1, 2019

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 3, 2019

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 3, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 1, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PA-P19-001

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

product manufactured in and exported from the U.S.

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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