Phase I/II clinical trial of piggyBac transposon-mediated CD19 CAR T cells for CD19-positive lymphoma

JRCT ID: jRCT2043240071

Registered date:20/08/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Patients with relapsed or refractory mature B-cell neoplasms with expected CD19-positive and not ind
• Date of first enrollment: 27/08/2024
• Target sample size: 50
• Study type: Interventional
• Intervention(s): On the day of administration of the investigational product, 2.0 x 106 (range 1.6 x 106 to 2.4 x 106) autologous T cells (CAR-T cells) expressing the chimeric antigen receptor (CAR) for CD19 per 1 kg body weight are administered. However, the maximum dose per dose should be 2.0 x 108 CAR-T cells.

Outcome(s)

Primary Outcome

Phase I: Dose-limiting toxicity rate within 28 days post-dose
Phase II part: overall response rate up to 90 days after treatment

Secondary Outcome

Phase I :
1. Safety endpoints
i. Incidence of adverse events from study enrollment to study completion or discontinuation
ii. Occurrence of defects from study enrollment to study completion or discontinuation
2. Efficacy endpoints
i. Treatment response at 28 days, 90 days, 24 weeks, and 52 weeks after the first dose for each subject using the pre-study lymphocyte removal chemotherapy assessment as baseline
ii. Survival at 52 weeks after the first dose
Phase II :
1. Safety endpoints
i. Incidence of adverse events from study entry to study completion or discontinuation
ii. Occurrence of defects from study entry to study completion or discontinuation
2. Efficacy endpoints
For the efficacy evaluation of the secondary efficacy endpoints related to the first dose, regardless of whether or not a repeat dose is administered, the date of the first dose will be Day 0, and the evaluation prior to the start of lymphocyte removal chemotherapy before the first dose will be used as the baseline.
Efficacy will be assessed by FDG-PET based on the Lugano Criteria. However, if evaluation by FDG-PET is difficult, or if CT or other methods or clinical progression is suspected, the Clinical Trial Coordinating Committee will be consulted and a comprehensive decision will be made after consultation with the investigators.
i. ORR and percentage of complete remission (CR) based on the best overall response up to 52 weeks after the first dose.
The percentage of tumor shrinkage based on CT evaluation will also be evaluated.
ii. Duration of response (DOR) and time to response (TTR) in patients with response after the first dose
iii.Progression Free Survival (PFS), Event Free Survival (EFS) and Overall Survival (OS) at 52 weeks after the first dose.

Key inclusion & exclusion criteria

• Age minimum: >= 12age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. The subject must have signed the consent document prior to the start of the clinical trial (if the subject is under 18 years of age, his or her surrogate must also have signed the document).
2. The subject must be at least 12 years old at the time of signing the consent document.
3. The subject must have one of the target diseases specified in the below among mature B-cell neoplasms.
Follicular lymphoma(FL), Diffuse large B-cell lymphoma, not otherwise specified(DLBCL, NOS), T-cell/histiocyte-rich large B-cell lymphoma(TFL), Primary mediastinal (thymic) large-B cell lymphoma(PMBCL), High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements(HGBL-DH/TH), High-grade B-cell lymphoma, not otherwise specified(HGBL, NOS). However, only grade 3B of the WHO grading system or transformed cases are included in FL.
4. The patient must be eligible for treatment evaluation by FDG-PET according to the Lugano Treatment Efficacy Criteria .
5. Karnofsky Perofprmance Status(for patients aged 16 years or older at screening) and Lansky score (for patients aged 15 years or younger at screening) must be 50 or higher.
6. Adequate organ function is maintained.
7. The patient must have vascular access (peripheral line or surgical indwelling line) to perform leukocyte apheresis procedures.
8. Consent not to donate blood, organs, sperm or semen, or oocytes to any other person until at least 12 months after the administration of the study product.
9. In women of childbearing potential, meet the requirements for pregnancy test results and contraceptive methods
10. Lactating women must agree not to breastfeed until at least 12 months after administration of the study product.
11. Males must meet contraceptive method requirements.
12. Have a life expectancy of at least 4 months after enrollment.

Exclude criteria

1.Patients who do not meet the inclusion criteria described above
2. Patients whose lesions are only of the central nervous system. However, patients with secondary CNS lesions may be enrolled.
3. Patients with EBV-LPD after hematopoietic stem cell transplantation
4. Patients with tumor invasion into major veins or arteries on CT imaging
5. Patients who have not previously received rituximab
6. Patients who have not received anthracyclines
7. Patients with a history of gene-modified T-cell therapy such as CD19.CAR-T cell therapy
8. Patients undergoing treatment for acute or chronic graft-versus-host disease (GVHD)
9. Patients with a history of Richter's transformation of chronic lymphocytic leukemia
10. Patients with deep vein thrombosis (DVT)/pulmonary embolism (PE) within 3 months or being treated for DVT/PE
11. Patients with a positive human immunodeficiency virus (HIV) nucleic acid test or human T-cell leukemia virus type 1 (HTLV-1) nucleic acid test
12. Patients with positive hepatitis B virus surface antigen (HBsAg) test
However, hepatitis B core antibody (HBcAb) and hepatitis B surface antibody (HBsAb) positive patients are not excluded if the hepatitis B virus nucleic acid test is below the detection limit.
13. Patients with active hepatitis C virus (HCV) infection
Not excluded in hepatitis C virus antibody (HCVAb)-positive cases if HCV nucleic acid test is less than the limit of detection
14. Patients with systemic infection with pathogenic microorganisms that cannot be controlled despite appropriate antimicrobial or antifungal or antiviral therapy
15. Patients with active autoimmune disease requiring immunosuppressive therapy
16. Patients with a history of other malignancies that have been cured or in remission for less than 5 years.Excluding some carcinoma in situ.
17. Patients with a history of certain cardiovascular diseases or surgery within 6 months prior to study enrollment
18. Patients with a history or current illness of clinically significant central nervous system diseases such as epilepsy, seizures, aphasia, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
19. Patients with other serious illnesses or psychiatric disorders that would preclude participation in the clinical trial
20. Patients with abnormal laboratory values of grade 3 or higher in CTCAE v 5.0 (except for hematopoietic disorders)
21. Pregnant female patients
22. Patients with allergies caused by raw materials used in the manufacture of this investigational product (bovine)
23. Other patients whom the investigator deems inappropriate to participate in the clinical trial.

Related Information

• Primary Sponsor: Takahashi Yoshiyuki