Phase I clinical study on the safety of HER2-specific chimeric antigen receptor (CAR) gene-modified T cell therapy

JRCT ID: jRCT2033220088

Registered date:25/05/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: HER2 positive osteosarcoma/soft tissue sarcoma and gynecologic malignancy
• Date of first enrollment: 06/05/2022
• Target sample size: 12
• Study type: Interventional
• Intervention(s): Administration of CAR-T cells produced from eripheral blood. The target dose assigned to the subject as CAR-expressing T cells (range: 8.3 x 10^5 cells/kg or 2.7 x 10^6 cells/kg) is intravenously infused.

Outcome(s)

• Primary Outcome: Dose-limiting toxicity (DLT) incidence at each dose

Secondary Outcome

1. Occurrence of adverse events (type, frequency, severity, etc.)
2. Antitumor efficacy of CAR-T cells therapy (RECIST ver 1.1, iRECIST)

Key inclusion & exclusion criteria

• Age minimum: >= 5age old
• Age maximum: < 65age old
• Gender: Both

Include criteria

SC1 (before apheresis)
1. Patients diagnosed with bone and soft tissue sarcoma or gynecologic malignancies who are refractory or intolerant to standard treatment or have relapsed or progressed after standard treatment
2. Patients aged 5 or more to less than 65 at the time of consent
3. Patients whose histopathological evaluation confirmed the expression of HER2
4. Patients with Karnofsky or Lansky scale of 50 percentage or more
5. Patients with target lesions
6. Patients with being able to safely perform apheresis
7. Patients who meet all of the following for the latest test values
-White blood cell count with 1500 per microliter or more
-Lymphocyte count with 500 per microliter or more
-Hemoglobin with 8.0 grams per deciliter or higher
-Platelet count with 75000 per microliter or more
-Total bilirubin with 1.5 times or less of the upper limit of reference value
-AST with 3 times or less of the upper limit of reference value
-ALT with 3 times or less of the upper limit of reference value
-Serum creatinine with 2.0 milligrams per deciliter or less
-SpO2 with 95 percentage or more (at rest, without oxygen inhalation)
8. Patients decided to be normal by echocardiography (left ventricular ejection fraction with 50 percentage or more or left ventricular diameter shortening rate with 30 percentage or more, and no abnormal electrocardiogram with pericardial effusion or requiring treatment)
9. Patients who are expected to survive for 3 months or more after obtaining consent
10. For participation in the study, written consent has been obtained from the subject or whose surrogate
11. Patients willing to participate in the long-term follow-up study

SC2 (before treatment)
Individuals who meet all SC1 eligibility criteria and meet the following criteria are eligible for inclusion:
1. Patients who can supply the investigational product
2. Individuals who are unwilling to withdraw consent after SC1 and are aware of the treatment
3. Patients treated with salvage chemotherapy who have a 4-week washout period between salvage chemotherapy and initiation of initial lymphodepletion chemotherapy

Exclude criteria

SC1 (pre-apheresis), SC2 (pre-treatment initiation)
1. Patients with active double cancers
2. Patients with concomitant active or serious infections
3. Patients with central nervous system metastases
4. Patients with a history of coronary artery disease or cerebrovascular disease, or patients with residual sequelae such as paralysis
5. Patients with uncontrolled hypertension (resting systolic >160mmHg or diastolic >100mmHg).
6. Patients with concomitant pulmonary fibrosis or interstitial pneumonia or a history of uncontrolled concomitant pulmonary disease and imaging findings suspicious for it.
7. Patients with uncontrolled diarrhea and diabetes mellitus
8. Patients with uncontrolled congestive heart failure, significant heart disease such as arrhythmia, or cerebrovascular disease.
New York Heart Association functional classification of heart failure in class III or IV-patients
9. Patients with serious complications (renal failure, hepatic failure, active peptic ulcer disease, intestinal paralysis, etc.)
10. Patients with concomitant psychosis or psychiatric symptoms who are judged to be difficult to participate in the study.
11. Patients with active autoimmune disease
12. HIV-positive patients, HTLV-1 positive patients
13. Patients who are HBsAg positive or HBc antibody positive and HBV-DNA positive, HCV positive patients
14. Subjects who participated in another clinical trial within 6 weeks prior to obtaining informed consent (SC1).
15. Individuals who received live vaccination in the 30 days prior to informed consent (SC1).
16. Pregnant or breastfeeding patients
17. Patients who do not give consent to adequate contraception
18. Patients with a history of drug or alcohol dependence or abuse
19. Individuals with a history of hypersensitivity reactions to ingredients or additives used in the investigational product (DMSO, albumins)
20. Patients with a history of hypersensitivity reactions to pretreatment and premedication
21. Other patients who are deemed inappropriate by the investigator or sub-investigator

Related Information

• Primary Sponsor: Yozo Nakazawa
• Source(s) of Monetary Support: BrightPath Biotherapeutics Co., Ltd.,Japan Agency for Medical Research and Development