Multiple CAR-T Cell Therapy Targeting AML

• ClinicalTrials.gov Identifier: NCT04010877
• Recruitment Status: Unknown
• First Posted: July 8, 2019
• Last Update Posted: September 19, 2019
• Sponsor: Shenzhen Geno-Immune Medical Institute
• Information provided by (Responsible Party): Shenzhen Geno-Immune Medical Institute

Study Description

Brief Summary:

The purpose of this clinical trial is to assess the feasibility, safety and efficacy of multiple CAR T-cell therapy which combines CAR T cells against CLL-1 with CAR T cells targeting CD123 or CD33 in patients with relapsed and refractory AML. The study also aims to learn more about the function of CAR T cells and their persistency in AML patients.

Condition or disease	Intervention/treatment	Phase
Acute Myeloid Leukemia	Biological: CLL-1, CD33 and/or CD123-specific CAR gene-engineered T cells	Phase 1; Phase 2

Detailed Description:

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

Over the past few years, several groups have demonstrated that CD33 and CD123 CAR T cells can eradicate AML in both preclinical and clinical trials. Nevertheless, relapse after CAR T therapy remains a critical problem in treating AML. Disease relapse can be caused by antigen escape and by the outgrowth of residual leukemia stem cells (LSCs) that are not effectively eliminated by CAR T cells. CLL-1 (C-type lectin-like molecule-1) is a transmembrane glycoprotein, which is overexpressed in LSCs but absent in HSCs (hematopoietic stem cells), suggesting that CLL-1 might be a promising target for novel AML therapy. In this study, we use CLL-1 CAR-T in combination with CD123 and/or CD33 CAR-T as a new strategy to address LSC issue and prevent relapse caused by antigen escape.

The T cells from patients or transplantation donors will be genetically modified with lentiviral CAR vector to recognize specific molecules (CD33, CD123 or CLL-1) expressed on the surface of AML cells. The engineered T cells will be applied to patients through intravenous delivery.

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Multi-center Phase I/II Clinical Trial of Multiple CAR T Cells for Treating Acute Myeloid Leukemia
• Actual Study Start Date: August 1, 2019
• Estimated Primary Completion Date: July 31, 2021
• Estimated Study Completion Date: December 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Multiple CAR T cells to treat AML; Multiple CAR T cells to treat AML	Biological: CLL-1, CD33 and/or CD123-specific CAR gene-engineered T cells; Infusion of CLL-1, CD33 and/or CD123-specific CAR-T cells

Outcome Measures

Primary Outcome Measures :

1. Safety of infusion [ Time Frame: 1 year ]
   Treatment-related adverse events are assessed by NCI CTCAE V4.0 criteria.

Secondary Outcome Measures :

1. Clinical response [ Time Frame: 1 year ]
   Objective responses (complete response (CR) + partial response (PR)) are assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.

Eligibility Criteria

• Ages Eligible for Study: 6 Months to 75 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age older than 6 months.
2. Confirmed expression of CLL-1, CD123 and/or CD33 in blast AML by immuno-histochemical staining or flow cytometry.
3. Karnofsky performance status (KPS) score is higher than 80 and life expectancy > 3 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, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
4. Pregnant or nursing women may not participate.
5. Use of glucocorticoid for systemic therapy within one week prior to entering the trial.
6. Previous treatment with any gene therapy products.
7. Patients, in the opinion of investigators, may not be able to comply with the study.

Contacts and Locations

Contacts

Contact: Lung-Ji Chang, Ph.D; 86-075586725195; c@szgimi.org

Locations

China, Guangdong

Shenzhen Geno-immune Medical Institute; Recruiting

Shenzhen, Guangdong, China, 518000

Sponsors and Collaborators

Shenzhen Geno-Immune Medical Institute

Investigators

• Principal Investigator: Lung-Ji Chang, Ph.D; Shenzhen Geno-Immune Medical Institute

More Information

• Responsible Party: Shenzhen Geno-Immune Medical Institute
• ClinicalTrials.gov Identifier: NCT04010877
• Other Study ID Numbers: GIMI-IRB-19004
• First Posted: July 8, 2019
• Last Update Posted: September 19, 2019
• Last Verified: September 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Shenzhen Geno-Immune Medical Institute:

AML; CAR T; CD33, CD123, CLL-1

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases