CAR-T CD19 for Acute Myelogenous Leukemia With t 8:21 and CD19 Expression

Giving CAR-T CD19 Transgenic T Cells for Acute Myeloid Leukemia Patients (AML) With t 8:21 and CD19 Expression

Chimeric antigen receptor (CAR-T) engineered T cells against the CD19 protein have been shown to be effective against acute lymphoma and lymphocytic leukemia and are approved by the US (FDA), European (EMA) and Health Basel.

However, little information exists on using CD19CAR for treatment of recurrent or irresponsible to previous treatment acute myeloid leukemia.

The proposed study will include patients with recurrent disease or those with disease irresponsible to common treatments and they will be treated with CAR-T CD19.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Biological: CAR-T CD19

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Arnon Nagler, MD; Phone Number: +972-3-530 5830; Email: Arnon.Nagler@sheba.health.gov.il

Study Locations

• Israel
  • Ramat Gan, Israel, 57261
    • Recruiting
    • Chaim Sheba Medical Center
    • Contact: M.D.
    • Contact: Arnon Nagler, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with recurrent acute myeloid leukemia (AML) including those after bone marrow transplantation or not responding to previous therapy, who have exhausted other approved relevant therapies such as chemotherapy protocols that are ineffective and with high toxicity, or FLT3 inhibitors in patients with FLT3 .

Exclusion Criteria:

• Heart disease including severe heart failure (NYHA III-IV), recent MI or CABG surgery (in previous six months), severe ventricular rhythm abnormalities, non ischemic heart disease, LVEF less than 45%
• Active involvement of CNS
• Active infection
• Pregnancy or lactation
• Graft versus host disease III-IV grade - Stroke or seizure in the last six months before treatment
• A positive result for the HIV infection (serum)
• Active hepatitis infection
• Life-threatening allergies to cyclophosphamide or fludarabine
• No informed consent signed by candidate
• Candidate enrolled in other 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: Cyclophosphamide, Flodarabine,CAR-T cells; The appropriate participants will undergo lymhopheresis to collect lymphocytes from PBMC peripheral blood. CAR T CD19 cells will be produced. The participants will receive cyclophosphamide 300 mg / m² and flodarabine 30 mg / m² lymphodeplition intravenously daily for 3 days. The CAR-T CD19 cells will be given on the 5 to 7 day post lymphodeplition .

Biological: CAR-T CD19; The CAR-T infusion will be given in IV infusion. The target dose is 1 X 106 positive CAR / kg T cells (range: 0.5-1.5X 106 CAR / kg positive T cells).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in the peripheral blood counts and differential	Will be evaluated by Coulter counter	Within two years from the introduction of the CAR-T CD19
The change in the antigen expression on the leukemic blasts	Will be evaluated by FACS	Within two years from the introduction of the CAR-T CD19
The change in the measurable residual disease	Will be evaluated by PCR	Within two years from the introduction of the CAR-T CD19
The change in the chromosomal translocations and aberrations	Will be evaluated by cytogenetics and FISH	Within two years from the introduction of the CAR-T CD19

Collaborators and Investigators

• Sponsor: Sheba Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2020
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: January 20, 2020
• First Submitted That Met QC Criteria: February 4, 2020
• First Posted (Actual): February 5, 2020

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Chimeric antigen receptors; Mixed phenotype acute leukemia; T cells.
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: 6482-19-SMC

Drug and device information, study documents

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