Gene Therapy Study for Familial Hemophagocytic Lymphohistiocytosis Using MUNC-CD34 and MUNC-T3 in Patients with UNC13D Gene Mutations

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What is this study about?

This clinical trial is focused on studying a rare disease called Familial Hemophagocytic Lymphohistiocytosis (FHL), which is caused by mutations in the UNC13D gene. The study is testing a new treatment involving gene therapy. This treatment uses a special type of cell therapy with two medications: MUNC13.4-CD34 suspension and MUNC13.4-T3 suspension. These medications are made from the patient’s own cells, which are modified outside the body using a lentiviral vector, a tool that helps deliver the correct gene into the cells. The modified cells are then given back to the patient through an intravenous infusion.

The purpose of the study is to evaluate the safety and effectiveness of this gene therapy in patients with FHL. Participants will receive a single dose of their own modified cells. The study will monitor the patients closely to see how their bodies respond to the treatment and to check for any side effects. The trial will also look at how well the treatment works in controlling the disease over time.

Throughout the study, researchers will observe the patients for any changes in their health, focusing on the safety of the treatment and its ability to help manage FHL. The study aims to provide valuable information on whether this new gene therapy can be a safe and effective option for patients with this genetic condition.

1 joining the study

Upon joining the study, you will be informed about the trial’s purpose, procedures, and potential risks and benefits. You will need to provide informed consent, which means you agree to participate after understanding all the information provided.

2 initial assessment

An initial assessment will be conducted to confirm your eligibility. This includes reviewing your medical history and conducting necessary tests to ensure you meet the criteria for participation.

3 mobilization procedure

The mobilization procedure involves preparing your body to collect stem cells. This may include medications to increase the number of stem cells in your bloodstream.

4 conditioning regimen

A conditioning regimen will be administered to prepare your body for the transplantation. This may involve treatments to suppress your immune system and make space for the new cells.

5 transplantation

You will receive a single dose of MUNC13.4-CD34 and MUNC13.4-T3 suspensions through an intravenous infusion. This process involves introducing the modified cells into your bloodstream.

6 post-transplant monitoring

After the transplantation, you will be closely monitored for any side effects or complications. Regular check-ups and tests will be conducted to assess your health and the effectiveness of the treatment.

7 follow-up assessments

Follow-up assessments will occur at various intervals, such as 3 months, 6 months, and 12 months after treatment. These assessments will evaluate the long-term safety and efficacy of the treatment.

Who Can Join the Study?

Patient aged from 3 months up to 17 years old.
Patient with a type of Familial Hemophagocytic Lymphohistiocytosis (FHL) caused by a change in the UNC13D gene.
Patient must have achieved complete remission, which means their clinical and laboratory test results have returned to normal.
Patient is eligible for a type of stem cell transplant called allogeneic HSCT if there is no matching donor available, or if a previous transplant did not work.
Parental or guardian’s signed informed consent is required for the patient to participate.
For patients who can have children: must agree to use a reliable method of birth control during the trial and for at least 12 months after receiving the treatment.
Patient must be affiliated with Social Security.

Who Cannot Join the Study?

Patients who do not have a confirmed diagnosis of Familial Hemophagocytic Lymphohistiocytosis (FHL) cannot participate. This is a rare genetic disorder affecting the immune system.
Patients who are not deficient in Munc 13.4 cannot participate. This refers to a specific protein that is lacking in some patients with FHL.
Patients who are not within the specified age range for the study cannot participate. The study is open to certain age groups only.
Patients who are not able to undergo the required medical procedures, such as the mobilisation procedure, conditioning regimen, or transplantation, cannot participate. These are steps involved in preparing and performing the treatment.
Patients who cannot receive the specific treatment involving LV-EF1a-UNC13D lentiviral vector gene modified autologous hematopoietic stem cells and transduced autologous T-cell cannot participate. This is a type of gene therapy using the patient’s own cells.
Patients who are not able to provide informed consent, or whose legal guardians cannot provide consent, cannot participate. This means understanding and agreeing to the study’s procedures and risks.

Where you can join this trial?

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Other Sites

Site Name	City	Country	Status
Hopital Beaujon	Clichy	France

Trial status

Country	Status	Recruitment Start
France	Not yet recruiting	09.09.2024

Trial locations

Investigated drugs:

MUNC-CD34 is a type of gene therapy used in this clinical trial. It involves taking a patient’s own stem cells, which are special cells that can develop into different types of blood cells. These stem cells are collected from the patient and then modified outside the body using a special vector, which is like a delivery system, to carry a healthy version of the UNC13D gene. This modified gene is intended to help correct the genetic problem that causes the disease. After the modification, the stem cells are returned to the patient’s body to help restore normal function.

MUNC-T3 is another part of the gene therapy approach in this trial. It involves using the patient’s own T-cells, which are a type of immune cell. These T-cells are collected and then modified in a similar way to the stem cells, using a vector to introduce the healthy UNC13D gene. The goal is to enhance the immune system’s ability to function properly by correcting the genetic defect in these cells. Once modified, the T-cells are returned to the patient’s body to help improve immune function.

LV-EF1a-UNC13D lentiviral vector is the tool used to modify the patient’s cells in this trial. It is a type of viral vector, which means it uses a virus that has been altered to be safe and is used to deliver the healthy UNC13D gene into the patient’s cells. This vector helps ensure that the new gene is inserted into the cells correctly, allowing them to produce the necessary proteins to help treat the disease.

Investigated diseases:

Haemophagocytic lymphohistiocytosis

Familial Hemophagocytic Lymphohistiocytosis (FHL) – Familial Hemophagocytic Lymphohistiocytosis is a genetic disorder that affects the immune system. It is characterized by an overactive immune response, where certain white blood cells, called histiocytes and lymphocytes, attack the body’s own tissues. This leads to symptoms such as prolonged fever, enlarged liver and spleen, and low blood cell counts. The disease progresses with excessive inflammation and can affect multiple organs, including the liver, brain, and bone marrow. Over time, the continuous immune activation can cause significant tissue damage. The condition is typically diagnosed in infancy or early childhood.

Trial ID:

2023-507334-24-00

Protocol code:

APHP240201

Trial Phase:

Human Pharmacology (Phase I) – First administration to humans

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Gene Therapy Study for Familial Hemophagocytic Lymphohistiocytosis Using MUNC-CD34 and MUNC-T3 in Patients with UNC13D Gene Mutations

What is this study about?

Who Can Join the Study?

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