Clinical trial NCT05477446: Safety and Efficacy of CD207 Targeted CAR-T Cell Therapy in Patients With R/R Langerhans Cell Histiocytosis
Official title: Safety and Efficacy of CD207 Targeted CAR-T Cell Therapy in Patients With Relapsed and Refractory (R/R) Langerhans Cell Histiocytosis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Langerhans Cell Histiocytosis
Keywords: CAR-T cell therapy
Langerhans Cell histiocytosis
CD207
Lead sponsor: Beijing Friendship Hospital
Sponsor class: OTHER
Collaborators: name: Beijing Boren Hospital
First posted: 2022-07-28
Enrollment: 12
Sex: ALL
Minimum age (years): 3
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single-arm study to evaluate the efficacy and safety of CD207 targeted CAR-T cell therapy in relapsed and refractory langerhans cell histiocytosis.

Detailed description: There are limited options for treatment of r/r langerhans cell histiocytosis. CD207 is expressed on the membrane surface of langerhans cells，and it is an ideal target for CAR-T. In this study, investigators will evaluate the safety and efficacy of CD207 targeted CAR- T cell therapy in patients with r/r langerhans cell histiocytosis. The primary goal is safety and efficiency assessment, including incidence and severity of adverse events and overall response rate.

Eligibility criteria: Inclusion Criteria:

1. Relapsed or refractory langerhans cell histiocytosis, defined as: 1) any relapse during standard chemotherapy; 2) not responding to standard chemotherapy; 3) not achieving CR after first cycle of second-line chemotherapy for relapsed langerhans cell histiocytosis;
2. 3-65 years old;
3. Expected survival time ≥ 3 months;
4. ECOG performance status of 0 or 1 (age ≥ 16 years) or Karnofsky performance status\> 80 (age \< 16 years) ;
5. With single or venous blood collection standards, and no other cell collection contraindications;
6. WBC ≥ 2.5×10\^9/L ，LY ≥ 0.7×10\^9/L，LY% ≥15%;
7. Serum creatinine ≤ 2.0 mg/dl;
8. ALT/AST ≤ 2.5 x ULN;
9. Total bilirubin ≤ 2.0 mg/dl;
10. PT:INR\<1.7, or PT is within 4s of the normal value;
11. Ability and willingness to adhere to the study visit schedule and all protocol requirements.

Exclusion Criteria:

1. Transduced CAR+ T lymphocytes\<5%, or expansion \<5 folds after stimulation with anti CD3/anti CD28 beads;
2. Pregnant or breasting-feeding women;
3. Active hepatitis B or hepatitis C infection;
4. Patients with HIV infection;
5. Uncontrolled active infection;
6. Use of systemic corticosteroid therapy;
7. Have received gene therapy, or any other CAR-T treatment;
8. Allergic to immunotherapy and related drugs;
9. History of heart disease requiring treatment, or poorly controlled hypertension;
10. Preceding and/or ongoing active ulcer or gastrointestinal bleeding;
11. Have received allogeneic hematopoietic stem cell transplantation, or eligible for allogeneic hematopoietic stem cell transplantation;
12. Severe central nervous system involvement;
13. Severe lung involvement;
14. Hyponatremia (serum sodium\<125mmol/L);
15. Hypokalemia (Serum kalium\<3.5mmol/L);
16. Those who need long-term anticoagulation treatment (warfarin or heparin);
17. Those who need long-term antiplatelet treatment (aspirin, dose\>300mg/d; clopidogrel, dose\>75mg/d);
18. Radiation therapy within 4 weeks prior to registration;
19. Uncontrolled, symptomatic, intercurrent illness including but not limited to infection, congestive heart failure, unstable angina, cardiac arrhythmias, mental illness, and other diseases that in the opinion of the investigator would pose an unacceptable risk to the subject;
20. Have a history of severe allergy;
21. Current enrollment in another study;
22. Patients with other contraindications considered unsuitable for participation in this study (according to investigator's judgement).

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: 2 years
measure: Incidence and Severity of Adverse Events (AEs)
timeFrame: 2 years
Secondary outcomes:
measure: Progression Free Survival (PFS) of CD207 CAR-T cell therapy in patients with r/r langerhans cell histiocytosis
timeFrame: 2 years
measure: Overall Survival (OS) of CD207 CAR-T cell therapy in patients with r/r langerhans cell histiocytosis
timeFrame: 2 years
measure: Effects of CD207 CAR-T cells on human immune system
timeFrame: 2 years
measure: Metabolism of CAR T-cells in vivo
timeFrame: 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
Study officials:
affiliation: Beijing Friendship Hospital
name: ZHAO Wang, MD
role: PRINCIPAL_INVESTIGATOR
References: