Evaluate the Safety and Efficacy of CD33 CAR-T in Patients With R/R AML

To Evaluate the Safety and Efficacy of CD33 CAR-T in Patients With Relapsed and Refractory Acute Myeloid Leukemia

This is an open label, phase I study to assess the safety and efficacy of CD33 CAR-T in patients with relapsed and refractory acute myeloid leukemia

Study Overview

• Status: Not yet recruiting
• Conditions: AML
• Intervention / Treatment: Biological: CD33 CAR-T

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The first affiliated hospital of medical college of zhejiang university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 70 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. All subjects must sign and date the Informed Consent before initiating any study specific procedures or activities;
2. Diagnosed as relapse/refractory (r/r) de novo or secondary acute myeloid leukemia (AML);
3. The expression of CD33 in AML blast is positive ;
4. The patient has recovered from the toxicity of previous treatment;
5. ECOG score ≤ 2 and expected survival period is not less than 3 months;

6. Adequate organ function defined as:

   AST ≤3×ULN; ALT ≤3×ULN; Total bilirubin ≤1.5×ULN; Serum creatinine ≤1.5×ULN, or CCR≥60 mL/min; Hemoglobin ≥60g/L ; Indoor oxygen saturation ≥92%; LVEF≥45%;

7. Pregnancy testing: females of childbearing potential must have a negative serum or urine pregnancy test;
8. From the use of study drug to 2 years after treatment, males and female of childbearing potential must agree to use an effective method of contraception

Exclusion Criteria:

1. Diagnosis of acute promyelocytic leukemia;
2. History or presence of a CNS disorder;
3. HBsAg or HBcAb are positive; HCV 、HIV and Syphilis antibody are positive, CMV DNA in peripheral blood is more than≥500 copies /mL;
4. History of severe hypersensitivity reaction;
5. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York Heart Association Class II or greater congestive heart failure, atrial fibrillation, or other clinically significant cardiac disease within 12 months before enrollment;
6. History of organ transplant surgery;
7. Required systemic application of immunosuppressive or other drugs;
8. Auto-SCT within the 3 months before enrollment;
9. Active autoimmune or inflammatory diseases of the nervous system (e.g., Guillain-Barre syndrome (GBS), amyotrophic lateral sclerosis (ALS)) and clinically active cerebrovascular diseases (e.g., cerebral edema, posterior reversible encephalopathy syndrome (PRES));
10. Requirement for urgent therapy due to ongoing or impending oncologic emergency (eg, leukostasis or tumor lysis syndrome (TLS)) ;
11. Presence or suspicion of a fungal, bacterial, viral, or other infection that is uncontrolled or requiring antimicrobials for management;
12. Live vaccine received within the ≤ 4 weeks before enrollment;
13. Persons with serious mental illness;
14. History of major surgical operations four weeks before enrollment;
15. History of alcoholism or substance abuse;
16. Was identified by the investigators as unsuitable to participate in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: CD33 CAR-T; Dose Escalation:After enrollment ,Participants complete the PBMC apheresis,then complete the Lymphocyte clearance,and then receive the dose climning test: 3×10e6/kg，6 ×10e6/kg，9×10e6/kg. Dose Expansion:Participants receive a single dose (at the MTD determined).	Biological: CD33 CAR-T; CD33 CAR-T is a new type CAR-T cells therapy for patients with acute myeloid leukemia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of Safety	Count the Incidence of adverse events	Up to 2 years after CD33CAR-T infusion
Changes in cytokine level after CD33 CAR-T infusion	Calculate the change of cytokine level in peripheral blood by flow cytometry after CAR-T infusion. Cytokines include IL-2、IL-6、IL-10、IFN-γ.	Up to 2 years after CD33CAR-T infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate(CRR)	Proportion of subjects who achieved morphological complete response (CR) and complete response with hematologic incomplete recovery (CRi)	Up to 2 years after CD33CAR-T infusion
Partial response Rate (PRR)	Proportion of subjects who achieved a partial response (PR)	Up to 2 years after CD33CAR-T infusion
Overall response Rate(ORR)	Proportion of subjects who achieved CR, CRi, or PR	Up to 2 years after CD33CAR-T infusion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Death from any cause from the beginning of cell transfusion	Up to 2 years after CD33CAR-T infusion
Recurrence free survival (RFS)	From remission to relapse or death of the subject (including all causes), whether the subject relapsed or died is unknown until the date of the last follow-up examination.	Up to 2 years after CD33CAR-T infusion
Event-free survival (EFS)	Counting from the beginning of cell transfusion until treatment failure, recurrence, or death (various causes). Subjects without any of these events were counted up to the last follow-up examination date. For patients without CR or CRi, EFS is calculated from the beginning of cell transfusion until disease progression or death. Based on the initial event.	Up to 2 years after CD33CAR-T infusion
MRD negative rate	The rate of MRD negative subjects was determined by flow cytometry.	Up to 2 years after CD33CAR-T infusion
Median BM Reduction	Changes of bone marrow primitive cells after cell transfusion from baseline.	Up to 2 years after CD33CAR-T infusion
Percentage of subjects disengaged from transfusion	Percentage of baseline transfusion-dependent subjects who were discharged from transfusion after cell transfusion.	Up to 2 years after CD33CAR-T infusion

Collaborators and Investigators

• Sponsor: Zhejiang University

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): August 2, 2022
• Primary Completion (ANTICIPATED): August 2, 2024
• Study Completion (ANTICIPATED): August 2, 2025

Study Registration Dates

• First Submitted: July 1, 2022
• First Submitted That Met QC Criteria: July 21, 2022
• First Posted (ACTUAL): July 25, 2022

Study Record Updates

• Last Update Posted (ACTUAL): July 25, 2022
• Last Update Submitted That Met QC Criteria: July 21, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: BG-CT-22-002(CD33)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No