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

Sponsor

Sheba Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04257175

Collaborator

(none)

Enrollment

Location

Arm

45.4

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Biological: CAR-T CD19	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 18, 2020

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

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).

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).

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Chaim Sheba Medical Center	Ramat Gan		Israel	57261

Sponsors and Collaborators

Sheba Medical Center

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Prof Arnon Nagler, M.D., M.Sc, Professor of Medicine Tel Aviv University, Director Hematology Division, Chaim Sheba Medical Center, Sheba Medical Center

ClinicalTrials.gov Identifier:

NCT04257175

Other Study ID Numbers:

6482-19-SMC

First Posted:

Feb 5, 2020

Last Update Posted:

Sep 24, 2021

Last Verified:

Sep 1, 2021

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Prof Arnon Nagler, M.D., M.Sc, Professor of Medicine Tel Aviv University, Director Hematology Division, Chaim Sheba Medical Center, Sheba Medical Center

Chimeric antigen receptors; Mixed phenotype acute leukemia; T cells.

Additional relevant MeSH terms:

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Study Results

No Results Posted as of Sep 24, 2021