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

Trial Summary

What is the purpose of this trial?

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. In this study, investigators attach the CD7 chimeric receptor with CD28 added to it to T cells. 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.

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.

What data supports the effectiveness of the treatment CD7-specific CAR T cells for blood cancer?

Research shows that CD7-specific CAR T cells have strong antitumor activity against T-cell acute lymphoblastic leukemia (T-ALL) in lab studies and animal models. These cells can effectively target and kill cancer cells while avoiding damage to normal cells, making them a promising treatment for blood cancers. ^{1 2 3 4 5}

Is CAR T-cell therapy targeting CD7 safe for humans?

CAR T-cell therapy targeting CD7 has shown promising results in treating certain blood cancers, but it also presents safety challenges. The therapy can cause significant side effects, including potential toxicity and adverse effects due to targeting healthy tissues, which researchers are actively working to mitigate. ^{1 2 3 6 7}

What makes CD7.CAR/28zeta CAR T cells unique compared to other treatments for blood cancer?

CD7.CAR/28zeta CAR T cells are unique because they target the CD7 antigen, which is consistently expressed in T-cell acute lymphoblastic leukemia (T-ALL), and use a novel method to prevent fratricide (self-destruction) by blocking CD7 expression on the T cells themselves. This approach enhances the effectiveness of the treatment against T-cell malignancies, which lack effective immunotherapies. ^{2 3 8 9 10}

Research Team

Rayne H. Rouce

Principal Investigator

Pediatrics, Baylor College of Medicine

LaQuisa HIll, MD

Principal Investigator

Baylor College of Medicine

Maksim Mamonkin, PhD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cells derived from CD7 nanobody exhibit robust antitumor potential against CD7-positive malignancies. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Engineering naturally occurring CD7- T cells for the immunotherapy of hematological malignancies. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Blockade of CD7 expression in T cells for effective chimeric antigen receptor targeting of T-cell malignancies. [2022]

4. United States 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

A novel CD7 chimeric antigen receptor-modified NK-92MI cell line targeting T-cell acute lymphoblastic leukemia. [2020]

6. Netherlands 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. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy: the Efficacy and Toxicity Balance. [2023]

8. Singapore pubmed.ncbi.nlm.nih.gov

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

9. England pubmed.ncbi.nlm.nih.gov

Preclinical targeting of human T-cell malignancies using CD4-specific chimeric antigen receptor (CAR)-engineered T cells. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

T cells redirected against CD70 for the immunotherapy of CD70-positive malignancies. [2021]