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T Lymphocytes Transduced With A Rv-Sfg.cd19.Cd28.4-1Bbzeta Retroviral Vector

This article explores the ongoing clinical trials of an advanced cancer treatment using genetically modified T lymphocytes. The therapy, known as CD19.CAR T cells, targets CD19-positive lymphoid diseases such as acute lymphoblastic leukemia (ALL) and non-Hodgkin’s lymphoma (NHL). These trials aim to evaluate the safety, feasibility, and effectiveness of this innovative approach in patients who have not responded to or relapsed after standard treatments.

Table of Contents

What is this treatment?

The treatment being studied is called “T Lymphocytes Transduced with RV-SFG.CD19.CD28.4-1BBzeta Retroviral Vector,” also known as CD19.CAR T cells or HD-CAR-1[1]. This is a type of cell therapy, which means it uses specially modified cells from the patient’s own body to fight disease.

How does it work?

This treatment involves taking a type of immune cell called T lymphocytes (a kind of white blood cell) from the patient’s blood. These cells are then genetically modified in a laboratory using a retroviral vector. This modification equips the T cells with a special receptor called a Chimeric Antigen Receptor (CAR) that targets a protein called CD19, which is found on the surface of certain cancer cells[1].

The modified T cells, now called CAR T cells, are then infused back into the patient’s body. These cells are designed to recognize and attack cancer cells that have the CD19 protein, potentially providing a more targeted and effective treatment for certain types of blood cancers[1].

What conditions does it target?

This treatment is being studied for patients with relapsed or refractory CD19+ lymphoid diseases. Specifically, it targets[1]:

  • Acute Lymphoblastic Leukemia (ALL): A type of blood and bone marrow cancer that affects white blood cells
  • Non-Hodgkin’s Lymphoma (NHL): A group of blood cancers that start in white blood cells called lymphocytes
  • Chronic Lymphocytic Leukemia (CLL): A type of cancer that affects blood and bone marrow
  • Diffuse Large B-cell Lymphoma (DLBCL): An aggressive type of NHL
  • Follicular Lymphoma (FL): A slow-growing type of NHL
  • Mantle Cell Lymphoma (MCL): A rare type of NHL

“Relapsed” means the cancer has returned after treatment, while “refractory” means the cancer has not responded to treatment[1].

Current Clinical Trial

A clinical trial called HD-CAR-1 is currently underway to study this treatment. It is a Phase I/II trial, which means it aims to test both the safety and effectiveness of the treatment[1].

Who is eligible for the treatment?

The trial has different eligibility criteria for adults and children[1]:

For Adults (18 years and older):

  • Confirmed CD19+ ALL, CLL, DLBCL, FL, or MCL
  • Relapsed or refractory disease (including “molecular relapse” with minimal residual disease)
  • Adequate kidney function and lymphocyte count

For Children (3 to 17 years):

  • Confirmed CD19+ ALL
  • Relapsed or refractory disease
  • Measurable disease at time of enrollment
  • Life expectancy of at least 12 weeks
  • Adequate performance status

There are also several exclusion criteria, such as certain ongoing infections or other medical conditions, that might prevent a person from participating in the trial[1].

Objectives of the Study

The main goals of this study are[1]:

  1. To evaluate the safety of the treatment at different doses
  2. To assess how well the modified T cells survive and function in the body
  3. To measure how effective the treatment is in reducing cancer burden
  4. To track how long the treatment’s effects last
  5. To monitor overall survival of patients after treatment

Safety Considerations

As with any new treatment, safety is a primary concern. The study will closely monitor for side effects, including[1]:

  • Cytokine Release Syndrome (CRS): A condition where the immune system becomes overly activated
  • Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS): A neurological side effect that can occur with some immunotherapies
  • Other potential toxicities, which will be graded according to standardized criteria

It’s important to note that this is an experimental treatment still under investigation. The full range of potential benefits and risks is not yet known, which is why careful study through clinical trials is necessary[1].

Aspect Details
Study Type Phase I/II integrated clinical trial
Target Conditions Relapsed or refractory CD19+ lymphoid diseases (ALL, NHL, CLL, DLBCL, FL, MCL)
Treatment Autologous T lymphocytes genetically modified with CD19-targeting CARs
Primary Objectives Evaluate safety, feasibility of dose escalation, toxicity assessment
Secondary Objectives Assess CAR T-cell survival, function, anti-tumor efficacy, patient outcomes
Key Eligibility (Adults) Confirmed CD19+ disease, relapsed/refractory status, adequate organ function
Key Eligibility (Pediatric) Age 3-18 years, CD19+ ALL, relapsed/refractory disease, measurable disease/MRD
Primary Endpoints Toxicity assessment, CRS/ICANS evaluation, dose-limiting toxicity, cell production metrics
Secondary Endpoints Response rates, survival outcomes, B-cell depletion correlation

FAQ

  • What is CD19.CAR T-cell therapy? CD19.CAR T-cell therapy is a type of immunotherapy that uses a patient's own T lymphocytes (a type of white blood cell) that have been genetically modified to target and attack cancer cells expressing the CD19 protein on their surface.
  • Who is eligible for these clinical trials? The trials are primarily for patients with relapsed or refractory CD19-positive lymphoid diseases, such as acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (NHL). Specific eligibility criteria vary based on age, disease type, and other health factors.
  • What are the main objectives of these trials? The main objectives are to evaluate the safety and feasibility of escalating doses of the modified T cells, assess their survival and function in the body, and determine their effectiveness in reducing disease burden and improving patient outcomes.
  • How is the treatment administered? The treatment is administered as a solution for infusion, given intravenously to the patient. The T cells are first collected from the patient, genetically modified, and then infused back into the patient's bloodstream.
  • What are some potential side effects being monitored? The trials are closely monitoring for side effects such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and other toxicities. The severity and frequency of these effects are being assessed using standardized criteria.

Ongoing Clinical Trials on T Lymphocytes Transduced With A Rv-Sfg.cd19.Cd28.4-1Bbzeta Retroviral Vector

  • Study on CD19+ Lymphoid Disease Using Genetically Modified T Cells for Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia and Non-Hodgkin’s Lymphoma

    Recruiting

    1 1 1
    Investigated drugs:
    Germany

Glossary

  • CAR T-cell therapy: A type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood, then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR).
  • CD19: A protein found on the surface of B cells, which are a type of white blood cell. CD19 is targeted by some cancer therapies, including CAR T-cell therapies for certain types of leukemia and lymphoma.
  • Acute Lymphoblastic Leukemia (ALL): A type of cancer in which the bone marrow makes too many immature lymphocytes (a type of white blood cell). It progresses rapidly and requires immediate treatment.
  • Non-Hodgkin's Lymphoma (NHL): A diverse group of blood cancers that develop from lymphocytes (a type of white blood cell). It is generally more common than Hodgkin's lymphoma.
  • Refractory disease: A disease that does not respond to treatment. The cancer may not shrink or may continue to grow even with treatment.
  • Relapsed disease: The return of a disease or the signs and symptoms of a disease after a period of improvement.
  • Cytokine Release Syndrome (CRS): A condition that may occur after treatment with some types of immunotherapy, such as CAR T-cell therapy. It is caused by a large, rapid release of cytokines into the blood from immune cells affected by the immunotherapy. Symptoms may include fever, nausea, headache, rash, rapid heartbeat, low blood pressure, and trouble breathing.
  • Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS): A neurological side effect that can occur with certain immunotherapies, particularly CAR T-cell therapy. Symptoms may include confusion, tremor, seizures, or difficulty with speech and writing.
  • Minimal Residual Disease (MRD): The small number of cancer cells that remain in the body during or after treatment. These cells are often too few to be detected using standard tests.
  • Leukapheresis: A laboratory procedure in which white blood cells are separated from a sample of blood. It is often used to collect T cells for CAR T-cell therapy.

References

  1. http://clinicaltrials.eu/trial/study-on-cd19-lymphoid-disease-using-genetically-modified-t-cells-for-patients-with-relapsed-or-refractory-acute-lymphoblastic-leukemia-and-non-hodgkins-lymphoma/