CAR T-Cell Therapy for Blood Cancer

Recruiting at 1 trial location

Overseen By Martha Arredondo

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must not be taking: Investigational agents

Disqualifiers: Active infection, Other cancer, Pregnancy, Cardiac issues, CNS abnormalities, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 5

Duration: 1 day

27 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for certain blood cancers, specifically T-cell leukemia and lymphoma. The treatment uses special T cells enhanced to better fight cancer by combining them with antibodies (proteins that latch onto cancer cells) and a booster called CD28 to help them grow and last longer in the body. This approach is known as CD7.CAR/28zeta CAR T cells therapy. Individuals dealing with recurrent or hard-to-treat T-cell leukemia or lymphoma, and who have a suitable donor for a possible stem cell transplant, might be a good fit for this trial. The goal is to determine if these enhanced T cells can effectively target and destroy cancer cells. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, you must have recovered from the acute toxic effects of prior chemotherapy at least one week before entering the study.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that CD7 CAR-T cells have been tested in people with T-cell leukemia and lymphoma. Previous studies found these treatments can be safe, but researchers continue to monitor for side effects. Some participants in earlier research experienced mild to moderate side effects, such as fever and chills, which are common with treatments like this.

These side effects occur because the body responds to the treatment, indicating an active immune system. More serious side effects have been rare, but ongoing studies aim to better understand how to manage them. Since this study is in an early phase, safety remains a top priority. The treatment is not yet approved by the FDA, so researchers are carefully studying how people react to it. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CD7.CAR/28zeta CAR T cells for blood cancer because they represent a cutting-edge approach that reprograms a patient’s own T cells to specifically target and destroy cancer cells. Unlike traditional treatments such as chemotherapy or radiation, which can affect both healthy and cancerous cells, this therapy is designed to hone in on cancer cells expressing the CD7 protein, potentially reducing side effects and increasing effectiveness. Additionally, this personalized treatment follows lymphodepleting chemotherapy, which prepares the body to accept and support the re-engineered T cells, potentially enhancing the overall impact against the cancer.

What evidence suggests that CD7.CAR/28zeta CAR T cells might be an effective treatment for blood cancer?

Research shows that CD7 CAR-T cell therapy, which participants in this trial will receive, holds promise for treating T-cell leukemia and lymphoma. This therapy modifies T cells, crucial blood cells that fight infections, enabling them to locate and attack cancer cells. Studies have found that these modified T cells can better target cancer cells using a special component called the CD7 chimeric receptor. This receptor enhances the T cells' ability to adhere to and destroy cancer cells. Early results suggest that adding a protein called CD28 extends the lifespan and effectiveness of these T cells in the body. While still under investigation, this approach offers hope for individuals with hard-to-treat blood cancers. ^{1 2 3 4 6}

Who Is on the Research Team?

Rayne H. Rouce

Principal Investigator

Pediatrics, Baylor College of Medicine

LaQuisa HIll, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for patients under 75 with recurrent T-cell blood cancers, suitable for stem cell transplant, and have a CD7-positive tumor. They must not have active infections or other recent cancers (except certain skin/breast/cervix cancers), be pregnant, or have severe heart/CNS issues.

Inclusion Criteria

I have been diagnosed with a type of T-cell lymphoma that has come back or didn't respond to treatment.

I am a candidate for a stem cell transplant and have a donor ready if my treatment works.

I am 75 years old or younger.

Exclusion Criteria

I had cancer other than skin, breast, or cervical, but was treated successfully over 2 years ago.

I am currently infected with HIV.

I am currently taking antibiotics for an infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Pre-Treatment Chemotherapy

Participants receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine to prepare for T-cell infusion

3 days

3 visits (in-person)

Treatment

Participants receive an infusion of CD7 chimeric receptor-T cells

1 day

1 visit (in-person)

Immediate Post-Treatment Monitoring

Participants are monitored for side effects and response to treatment, remaining locally for at least 3 weeks

3 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with regular blood tests and scans

15 years

Regular visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• CD7.CAR/28zeta CAR T cells
• Cyclophosphamide
• Fludarabine

Trial Overview The study tests a new therapy where T cells from the patient's blood are modified in the lab to fight cancer better. These cells are equipped with an anti-CD7 antibody and CD28 protein to help them last longer and kill more cancer cells.

How Is the Trial Designed?

Group I: CD7.CAR/28zeta CAR T Cells Experimental Treatment 1 Intervention

Four dose levels will be evaluated. The T cells will be administered following lymphodepleting chemotherapy with cyclophosphamide and fludarabine.

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Cancer Prevention Research Institute of Texas

Collaborator

Trials

55

Recruited

98,900+

The Leukemia and Lymphoma Society

Collaborator

Trials

87

Recruited

26,200+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

Published Research Related to This Trial

CAR-T cell therapy is emerging as a promising immunotherapy for hematological cancers, particularly by targeting immune checkpoint proteins on tumor cells.

The review discusses various CAR-T cells targeting proteins like CD70, CD47, and PDL-1, which can effectively reduce tumor cells by overcoming inhibitory signaling pathways, suggesting a potential for improved cancer treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cells Targeting Immune Checkpoint Pathway Players. Golubovskaya, V.[2022]

The study developed a CAR (CD4CAR) that enables CD8+ T cells to target and eliminate CD4+ T-cell lymphomas, showing effectiveness in both laboratory and patient-derived samples.

In mouse models of aggressive T-cell lymphoma, CD4CAR T cells not only suppressed tumor growth but also significantly extended survival, suggesting their potential as a new treatment option for patients with peripheral T-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical targeting of human T-cell malignancies using CD4-specific chimeric antigen receptor (CAR)-engineered T cells. Pinz, K., Liu, H., Golightly, M., et al.[2018]

Genetically modified T cells targeting CD70 show promise for treating a wide range of hematologic malignancies and some solid tumors, expanding the potential of T-cell therapies beyond B cell-derived cancers.

The study demonstrated that CD70-specific T cells can effectively recognize and kill tumor cells, leading to sustained regression of tumors in mouse models, indicating their potential as a new immunotherapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T cells redirected against CD70 for the immunotherapy of CD70-positive malignancies. Shaffer, DR., Savoldo, B., Yi, Z., et al.[2021]

CD7-CAR T cells, which are modified to avoid fratricide by using naturally occurring CD7- T cells, showed strong antitumor activity against T-cell acute lymphoblastic leukemia (T-ALL) in both laboratory and mouse models.

In a comparison of CD19-CAR T cells, those derived from CD7- T cells demonstrated enhanced antitumor effects, and a higher presence of CD7-low expressing T cells was associated with better patient responses in a clinical study, suggesting a promising avenue for immunotherapy in hematological malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering naturally occurring CD7- T cells for the immunotherapy of hematological malignancies. Freiwan, A., Zoine, JT., Crawford, JC., et al.[2023]

The development of CD7ΔT cells allows for the safe use of CD7-CAR-T therapy by preventing fratricide among T cells, which is a major issue when targeting the CD7 antigen that is present on both normal and malignant T cells.

CD7ΔCD7-CAR-T cells demonstrated strong antitumor activity against CD7-positive tumors in laboratory models, indicating their potential for effective treatment in patients with CD7+ malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cells derived from CD7 nanobody exhibit robust antitumor potential against CD7-positive malignancies. Chen, D., You, F., Xiang, S., et al.[2021]

A novel immunotherapy targeting CD7 in T-cell acute lymphoblastic leukemia (T-ALL) was developed using CAR T cells, which showed over 99% CD7 expression in diagnostic samples, including aggressive subtypes.

To prevent fratricide (self-destruction of T cells), a new method called protein expression blocker (PEBL) was used, allowing CAR T cells to effectively target and kill CD7+ leukemic cells without harming themselves, demonstrating strong anti-leukemic activity in both lab and patient-derived models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blockade of CD7 expression in T cells for effective chimeric antigen receptor targeting of T-cell malignancies. Png, YT., Vinanica, N., Kamiya, T., et al.[2022]

CAR-T cell therapy has shown remarkable efficacy in treating B cell malignancies, including leukemia, lymphoma, and multiple myeloma, with high response rates, but it comes with significant safety concerns.

The most serious side effects of CAR-T therapy are cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which require supportive care and specific treatments like tocilizumab and steroids to manage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy: the Efficacy and Toxicity Balance. Chohan, KL., Siegler, EL., Kenderian, SS.[2023]

CD7-CAR-NK-92MI cells, particularly the bivalent dCD7-CAR-NK-92MI variant, demonstrated strong anti-tumor activity against T-cell acute lymphoblastic leukemia (T-ALL) in both cell lines and primary tumor samples, indicating their potential efficacy as a treatment.

The bivalent CAR-NK cells showed enhanced cytotoxicity and increased secretion of immune response markers like Granzyme B and interferon γ, and they significantly inhibited disease progression in xenograft mouse models, suggesting a promising new approach for T-ALL therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel CD7 chimeric antigen receptor-modified NK-92MI cell line targeting T-cell acute lymphoblastic leukemia. You, F., Wang, Y., Jiang, L., et al.[2020]

CAR T cell therapy has shown great promise in treating certain blood cancers, but it can lead to serious side effects, including potentially fatal toxicities from cytokine release and off-target effects that harm healthy tissues.

Recent strategies to improve safety include modifying CAR structures and incorporating elements like switch molecules and suicide genes to reduce the toxic effects of CAR T cells on normal tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategies for modifying the chimeric antigen receptor (CAR) to improve safety and reduce toxicity in CAR T cell therapy for cancer. Sayadmanesh, A., Yekehfallah, V., Valizadeh, A., et al.[2023]

In a clinical trial involving patients with relapsed and refractory T-lymphoblastic leukemia/lymphoma (T-ALL/LBL), autologous CD7-CAR T cells achieved a high complete remission rate of 87.5%, indicating strong efficacy in treating this aggressive cancer.

The treatment was well-tolerated, with most patients experiencing only mild cytokine release syndrome and no severe toxicities, suggesting a favorable safety profile for this innovative immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous Nanobody-Derived Fratricide-Resistant CD7-CAR T-cell Therapy for Patients with Relapsed and Refractory T-cell Acute Lymphoblastic Leukemia/Lymphoma. Zhang, M., Chen, D., Fu, X., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03690011

Study Details | NCT03690011 | Cell Therapy for High Risk ... 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 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39845313/

The efficacy and safety of CD7 chimeric antigen receptor T ... This study summarizes the currently published clinical research results on CD7 CAR-T cells and evaluates the safety and effectiveness of CD7 CAR-T cell therapy.

3. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1478888/full

The efficacy and safety of CD7 chimeric antigen receptor T- ... Introduction: CD7 chimeric antigen receptor T-cell (CAR-T cell) therapy is an emerging method for treating hematological malignancies, and is ...

4. bloodcancerunited.org bloodcancerunited.org/research/award/novel-cd7-car-t-cells-refractory-t-cell-malignancies-affecting-pediatric-and-aya-patients

Novel CD7 CAR T-cells for refractory T-cell malignancies ... CAR T-cells have been very effective in patients with difficult-to-treat B-cell blood cancers but have lagged behind in T-cell blood cancers.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12327587/

CD7 CAR-T therapy: current developments, improvements, ... CD7 CAR-T therapy is one of the most extensively studied approaches for treating r/r T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11752923/

The efficacy and safety of CD7 chimeric antigen receptor T ... This study summarizes the currently published clinical research results on CD7 CAR-T cells and evaluates the safety and effectiveness of CD7 CAR-T cell therapy.