Clinical Trial

Disease: T-cell Acute Lymphoblastic Leukaemia, T-ALL, (NCT03690011)

Disease info:

T-cell acute lymphoblastic leukaemia (T-ALL) is a type of acute leukaemia meaning that it is aggressive and progresses quickly. It affects the lymphoid-cell-producing stem cells, in paticular a type of white blood cell called T lymphocytes as opposed to acute lymphoblastic leukaemia (ALL) which commonly affects B lymphocytes. A lymphoid stem cell becomes a lymphoblast cell and then one of three types of lymphocytes (white blood cells):

  • B lymphocytes that make antibodies to help fight infection.
  • T lymphocytes that help B lymphocytes make the antibodies that help fight infection.
  • Natural killer cells that attack cancer cells and viruses.

There are no specific signs or symptoms which would allow a diagnosis of T-ALL to be made. The most common signs and symptoms are caused by the bone marrow being unable to produce enough normal blood cells. T-ALL often causes swolen lymph nodes in the middle part of the chest (mediastinum) which may affect breathing or the circulation. The results of a simple blood count will usually indicate leukaemia although, rarely, a blood count may be normal. Virtually all patients with T-ALL will have bone marrow samples taken to confirm the diagnosis and to help to determine exactly what type of leukaemia a patient has. 

The main ways in which leukaemia is treated are:

  • Chemotherapy – Cell-killing drugs. Steroids are normally used along with chemotherapy for T-ALL
  • Radiation therapy – Usually only given as part of a stem cell transplant in T-ALL
  • Stem cell transplant – Younger/fitter patients may be given a stem cell transplant (bone marrow transplant). This is done using healthy stem cells from a donor. This is also done for T-ALL if chemotherapy does not cure the disease. 
Frequency:
The American Cancer Society’s estimates approximately 6,540 new cases of Acute Lymphoblastic Leukaemia (ALL) in 2023, accounting for less than 1% of all cancers in the United States.
Official title:
Cell Therapy for High Risk T-cell Malignancies Using CD7-Specific CAR Expressed on Non-Edited T Cells (CRIMSON-NE)
Who:

Contact

Name: LaQuisa Hill, MD

Phone: 713-441-1450

Email: LaQuisa.Hill@bcm.edu


Name: Martha Arredondo

Phone: 832-824-1201

Email: Martha.Arredondo@bcm.edu

 

Sponsor:

Baylor College of Medicine

Partners:

The Methodist Hospital Research Institute

Center for Cell and Gene Therapy, Baylor College of Medicine

Locations:

United States, Texas

Houston Methodist Hospital, Houston, Texas, United States, 77030

Texas Children's Hospital, Houston, Texas, United States, 77030

 

Study start:
Aug. 2, 2021
Enrollment:
21 participants
Gene editing method:
CRISPR-Cas9
Gene:
Cluster of Differentiation 7 (CD7)
Delivery method:
Electroporation - Ex-vivo
Trial link:
https://clinicaltrials.gov/ct2/show/study/NCT03690011
Other links:

LinkAcute Lympoblastic Leukemia Disease informationLinkAcute Lympoblastic Leukemia frequencyLinkCD7-edited T cells expressing a CD7-specific CAR for the therapy of T-cell malignanciesLinkThe Role of Gene Editing Within CAR T-Cell Therapy Development - Interview with Professor Waseem Qasim

Indicator
IND Enabling Pre-clinical
Phase I Safety
Phase II Safety and Dosing
Phase III Safety and Efficacy

Status: Active recruiting

Description

Patients eligible for this study have a type of blood cancer called T-cell leukemia or lymphoma (lymph gland cancer).

The body has different ways of fighting infection and disease. This study combines two different ways of fighting disease with antibodies and T cells. Antibodies are types of proteins that protect the body from bacterial and other diseases. T cells, or T lymphocytes, are special infection-fighting blood cells that can kill other cells including tumor cells. Both antibodies and T cells have been used to treat cancer; they have shown promise, but have not been strong enough to cure most patients.

T cells can kill tumor cells but there normally are not enough of them to kill all the tumor cells. Some researchers have taken T cells from a person's blood, grown more of them in the laboratory and then given them back to the person.

The antibody used in this study is called anti-CD7. This antibody sticks to T-cell leukemia or lymphoma cells because of a substance on the outside of these cells called CD7. CD7 antibodies have been used to treat people with T-cell leukemia and lymphoma. For this study, anti-CD7 has been changed so that instead of floating free in the blood it is now joined to the T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor.

In the laboratory, investigators have also found that T cells work better if they also add proteins that stimulate T cells, such as one called CD28. Adding the CD28 makes the cells grow better and last longer in the body, thus giving the cells a better chance of killing the leukemia or lymphoma cells. Finally, to make sure the T cells are able to grow and expand properly without accidentally targeting themselves (because they also have CD7 on their surface), investigators have removed the CD7 gene in the T cells using a genome editing technique called CRISPR-Cas9. Investigators have repeatedly shown in the laboratory and in our animal studies that removing the CD7 genes in T cells using CRISPR-Cas9 before adding the CAR to the cells helps them expand and kill better, and does not interfere with the other functions of the T cells.

In this study, investigators attach the CD7 chimeric receptor with CD28 added to it to T cells that have had CD7 removed from their surface. Investigators will then test how long the cells last. These CD7 chimeric receptor T cells with CD28 are investigational products not approved by the Food and Drug Administration.

Last updated: Dec. 28, 2023
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