Safety and Efficacy of CD207 Targeted CAR-T Cell Therapy in Patients With R/R Langerhans Cell Histiocytosis

Safety and Efficacy of CD207 Targeted CAR-T Cell Therapy in Patients With Relapsed and Refractory (R/R) Langerhans Cell Histiocytosis

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Langerhans Cell Histiocytosis
• Intervention / Treatment: Biological: CD207 CAR-T cells

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.

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: ZHAO Wang, MD; Phone Number: 86-63139862; Email: wangzhao@ccmu.edu.cn

Study Locations

• China
  • Beijing, China, 100050
    • Beijing Friendship Hospital, Capital Medical University
    • Contact: Zhao Wang, PhD; Phone Number: 86-63139862; Email: wangzhao@ccmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CD207 CAR-T cells; Cohort 1 will receive 1 x 10^6 CAR+ T cells/kg. Cohort 2 will receive 3 x 10^6 CAR+ T cells/kg. Cohort 3 will receive 5 x 10^6 CAR+ T cells/kg. Cohort 4 will receive 1 x 10^7 CAR+ T cells/kg.	Biological: CD207 CAR-T cells; Single dose of CD207 CAR-T cells administered IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	The number of cases with complete response (CR) and partial response (PR) after treatment as a percentage of the total cases.	2 years
Incidence and Severity of Adverse Events (AEs)	Treatment-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0)	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) of CD207 CAR-T cell therapy in patients with r/r langerhans cell histiocytosis	PFS will be assessed from the first CAR-T cell infusion to death from any cause or the first assessment of progression.	2 years
Overall Survival (OS) of CD207 CAR-T cell therapy in patients with r/r langerhans cell histiocytosis	OS will be assessed from the first CAR-T cell infusion to death from any cause.	2 years
Effects of CD207 CAR-T cells on human immune system	Dynamic changes of T cell subset and immune globulin.	2 years
Metabolism of CAR T-cells in vivo	Absorption, distribution and metabolism of CD207-CAR T cells in vivo.	2 years

Collaborators and Investigators

• Sponsor: Beijing Friendship Hospital
• Collaborators: Beijing Boren Hospital
• Investigators: Principal Investigator: Zhao Wang, MD, Beijing Friendship Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2022
• Primary Completion (Anticipated): June 1, 2025
• Study Completion (Anticipated): August 1, 2025

Study Registration Dates

• First Submitted: July 18, 2022
• First Submitted That Met QC Criteria: July 25, 2022
• First Posted (Actual): July 28, 2022

Study Record Updates

• Last Update Posted (Actual): July 28, 2022
• Last Update Submitted That Met QC Criteria: July 25, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: CAR-T cell therapy; Langerhans Cell histiocytosis; CD207
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lymphatic Diseases; Lung Diseases; Lung Diseases, Interstitial; Histiocytosis, Langerhans-Cell; Histiocytosis
• Other Study ID Numbers: BRYY-IIT-LCYJ-2022-002

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