Multi-CAR T Cell Therapy for Acute Myeloid Leukemia

Multi-center Phase I/II Clinical Trial of Multi-CAR T Cell Therapy for Acute Myeloid Leukemia

The purpose of this clinical trial is to assess the feasibility, safety and efficacy of multi-CAR T cell therapy targeting different AML surface antigens in patients with relapsed or refractory acute myeloid leukemia (AML). Another goal of the study is to learn more about the function of the multi-CAR T cells and their persistency in the patients.

Study Overview

• Status: Unknown
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Biological: Muc1/CLL1/CD33/CD38/CD56/CD123-specific gene-engineered T cells

Detailed Description

Acute myeloid leukemia (AML) is a malignant disease characterized by the rapid growth of myeloblasts that build up in the bone marrow and interfere with the production of normal blood cells.

In this study, the patients' own T cells will be genetically modified with lentiviral vectors expressing chimeric antigen receptors. The multi-CAR T cells recognize specific molecules such as CD33, CD38, CD123, CD56, MucI, and CLL1, which are often found expressed on the surface of AML cells. The engineered CAR T cells will be infused into patients.

The purpose of this clinical study is to assess the feasibility, safety and efficacy of the multi-CAR T cell therapy against AML. Another goal of the study is to learn more about the function of the multi-CAR T cells and their persistency in the patients.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510282
      • Recruiting
      • Zhujiang Hospital of Southern Medical University
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Shenzhen Geno-Immune Medical Institute
  • Yunnan
    • KunMing, Yunnan, China, 650000
      • Recruiting
      • Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center
      • Contact: Xun Lai, MS; Phone Number: 13577096609; Email: 1729112214@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age older than 2 years.
2. CD33, CD38, CD56, CD123, MucI, and CLL1 expression can be identified in the malignant cells by immuno-histochemical staining or flow cytometry.
3. Karnofsky performance status (KPS) score is higher than 80 and life expectancy > 2 months.
4. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: cardiac ejection fraction ≥ 50%, oxygen saturation ≥ 90%, creatinine ≤ 2.5 × upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal, total bilirubin ≤ 2.0mg/dL.
5. Hgb≥80g/L.
6. No cell separation contraindications.
7. Abilities to understand and the willingness to provide written informed consent.

Exclusion Criteria:

1. Sever illness or medical condition, which would not permit the patient to be managed according to the protocol, including active uncontrolled infection.
2. Active bacterial, fungal or viral infection not controlled by adequate treatment.
3. Known HIV or hepatitis B virus (HBV) infection.
4. Pregnant or nursing women may not participate.
5. History of glucocorticoid for systemic therapy within the week prior to entering the test.
6. Previously treatment with any gene therapy products.
7. Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.

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: Single arm; CAR T cells to treat AML	Biological: Muc1/CLL1/CD33/CD38/CD56/CD123-specific gene-engineered T cells; Infusion of Muc1/CLL1/CD33/CD38/CD56/CD123-specific gene-engineered T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
percentage of patients with treatment related adverse effect	percentage of participants with treatment-related adverse events, as assessed by physical exam, vital signs, standard clinical labs and so on.	a year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti tumor activity of fourth generation CAR-T cells in patients with relapsed or refractory AML	scale of CAR copies and leukemic cell burden (for efficacy)	a year

Collaborators and Investigators

• Sponsor: Shenzhen Geno-Immune Medical Institute
• Collaborators: Yunnan Cancer Hospital; Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2017
• Primary Completion (Anticipated): December 31, 2019
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: July 14, 2017
• First Submitted That Met QC Criteria: July 17, 2017
• First Posted (Actual): July 19, 2017

Study Record Updates

• Last Update Posted (Actual): October 17, 2018
• Last Update Submitted That Met QC Criteria: October 15, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: AML; CAR T; Muc1,CLL1, CD33, CD38, CD56, and/or CD123
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: GIMI-IRB-17015

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