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

Tracking Information

• First Submitted Date: July 4, 2019
• First Posted Date: July 8, 2019
• Last Update Posted Date: September 19, 2019
• Actual Study Start Date: August 1, 2019
• Estimated Primary Completion Date: July 31, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 4, 2019)

Safety of infusion [ Time Frame: 1 year ]

Treatment-related adverse events are assessed by NCI CTCAE V4.0 criteria.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 4, 2019)

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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Multiple CAR-T Cell Therapy Targeting AML
• Official Title: Multi-center Phase I/II Clinical Trial of Multiple CAR T Cells for Treating Acute Myeloid Leukemia
• 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.

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 Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Acute Myeloid Leukemia

Intervention

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

Study Arms

Experimental: Multiple CAR T cells to treat AML

Multiple CAR T cells to treat AML

Intervention: Biological: CLL-1, CD33 and/or CD123-specific CAR gene-engineered T cells

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: July 4, 2019): 10
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2023
• Estimated Primary Completion Date: July 31, 2021 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Months to 75 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04010877
• Other Study ID Numbers: GIMI-IRB-19004
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Shenzhen Geno-Immune Medical Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Shenzhen Geno-Immune Medical Institute
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Shenzhen Geno-Immune Medical Institute
• Verification Date: September 2019