Clinical trial NCT04317885: A Study Evaluating Safety and Efficacy of C-CAR039 Treatment in NHL Subjects
Official title: A Study Evaluating Safety and Efficacy of C-CAR039 Treatment in Relapsed or Refractory NHL Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-Hodgkin's B-cell Lymphoma
Lead sponsor: Shanghai Tongji Hospital, Tongji University School of Medicine
Sponsor class: OTHER
Collaborators: name: Shanghai AbelZeta Ltd.
First posted: 2020-03-23
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The trial is a single arm, single-center, non-randomized phase I clinical trial which is designed to evaluate the safety and efficacy of C-CAR039 in treatment of relapsed or refractory NHL patients

Detailed description: This study plans to enroll 25 patients to assess the safety and efficacy of C-CAR039. Subjects who meet the eligibility criteria will receive a single dose of C-CAR039 injection.

The study will include the following sequential phases: Screening, Apheresis and C-CAR039 manufacturing, Bridging (if needed), Baseline, lymphodepletion, C-CAR039 infusion, and Follow-up Visit.

Eligibility criteria: Inclusion Criteria:

* 1. Volunteered to participate in this study and signed informed consent
* 2. Age 18-75 years old, male or female
* 3. CD19 or CD20 positive DLBCL (including PMBCL and tFL), FL and MCL confirmed by cytology or histology according to WHO2016 criteria. For CD20-positive subjects, they should have received at least one regimen containing anti-CD20-targeted therapy (such as rituximab). If they do not complete the regimen due to intolerance, the cause should be recorded.
* 4. Relapsed or refractory disease after ≥ 2 lines (for FL, at least 3 lines) of standard therapy or relapsed after autologous stem cell transplantation (ASCT)
* 5. At least one measurable lesion (LDi ≥ 1.5 cm);
* 6. At least two weeks from last treatment (radiation, chemotherapy, mAb, etc) to apheresis;
* 7. LVEF≥ 50% (ECHO)
* 8. No active pulmonary infections, normal or mild impaired pulmonary function and SpO2≥92%
* 9. Laboratory criteria: ANC≥1.0×109/L; Platelets≥50×109/L; Serum total bilirubin ≤1.5x ULN; Creatinine≤ ULN; AST and ALT≤3x ULN
* 10. No contraindications of apheresis;
* 11. Expected survival ≥ 3months
* 12. ECOG score 0 or 1

Exclusion Criteria:

* 1. Have a history of allergy to cellular products;
* 2. According to the NYHA cardiac function grading standards, patients with grade III or IV cardiac dysfunction;
* 3. A history of craniocerebral trauma, disturbance of consciousness, epilepsy, cerebrovascular ischemia, cerebrovascular hemorrhagic disease, etc.;
* 4. Patients with central nervous system involvement;
* 5. Patients with autoimmune diseases, immunodeficiency or other conditions requiring immunosuppressive therapy;
* 6. Received allogeneic hematopoietic stem cell transplantation before;
* 7. Previous use of any CAR T cell product or other genetically modified T cell therapy;
* 8. Autologous stem cell transplantation within 6 weeks before infusion;
* 9. Severe active infections (except for simple urinary tract infections, bacterial pharyngitis), or currently undergoing intravenous infusion of antibiotics. However, prophylactic antibiotic, antiviral and antifungal infection treatments are permissible;
* 10. Live vaccination within 4 weeks prior to apheresis;
* 11. People infected with HIV, HBV, HCV and TPPA/RPR, and carriers with HBV;
* 12. A history of alcohol abuse, drug use or mental illness;
* 13. Subjects who are not sterilized and have any of the following conditions:

  1. are pregnant/lactating; or
  2. planned pregnancy during the trial; or
  3. being fertile and unable to use effective contraception;
* 14. Severe hypersensitivity to fludarabine or cyclophosphamide;
* 15. A history of other primary cancers other than the following:

  1. Non-melanoma tumors such as basal cell carcinoma of the skin that are cured by excision
  2. Cured in situ cancers such as cervical, bladder, or breast cancer
* 16. The investigators consider that the subject has other conditions that are not suitable for this trial.

Primary outcomes:
measure: Incidence and severity of adverse events
timeFrame: Up to 12 weeks after C-CAR039 infusion
Secondary outcomes:
measure: Overall Response rate (ORR)
timeFrame: Up to 24 Months after C-CAR039 infusion
measure: Duration of response (DOR)
timeFrame: Up to 24 Months after C-CAR039 infusion
measure: Progression-free survival (PFS)
timeFrame: Up to 24 Months after C-CAR039 infusion
measure: Overall survival (OS)
timeFrame: Up to 24 Months after C-CAR039 infusion
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Tongji Hospital, Tongji University School of Medicine
state: Shanghai
Study officials:
affiliation: Shanghai Tongji Hospital, Tongji University School of Medicine
name: Aibin Liang, MD, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: