CD19 CAR-T Cells for Leukemia and Lymphoma

(MULTIPRAT Trial)

Not currently recruiting at 1 trial location

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must not be taking: Corticosteroids

Disqualifiers: Severe infection, GVHD >grade II, others

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

Compensation: Varies

Number of Visits: 1

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine a safe dose of a new cell therapy called CD19 CAR-T cells. This therapy combines T cells (a type of immune cell) with an antibody to target cancer cells in individuals with certain blood cancers, such as leukemia or lymphoma. The trial seeks to prevent infections and cancer relapse after a bone marrow transplant. Participants should have CD19-positive leukemia or lymphoma, be undergoing a bone marrow transplant, and may still have some cancer cells present or have relapsed. As a Phase 1 trial, the 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 requires that you stop taking other investigational antiviral or antitumor therapies for one month before joining. If you are currently on corticosteroids for graft versus host disease, you cannot participate.

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

Research has shown that CD19 CAR T cells, a treatment for blood cancers like leukemia and lymphoma, have a promising safety record. Studies indicate that this treatment is generally safe, with most side effects being manageable. While some individuals might experience mild to moderate side effects, serious complications occur less frequently.

For instance, one study found that CD19 CAR T cells have a manageable safety profile, and many patients demonstrated a good overall survival rate. Although these treatments are still under investigation and not yet FDA-approved for this specific trial, the safety data from previous studies may reassure those considering participation in a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for leukemia and lymphoma, which often rely on chemotherapy or radiation, the CD19 CAR-T cell therapy is a cutting-edge approach that uses the body's own immune cells to fight cancer. This treatment involves engineering T cells to specifically target and destroy cancer cells that express the CD19 protein, offering a more precise attack on the disease. Researchers are excited because this therapy not only has the potential to be more effective in targeting cancer cells but also minimizes damage to healthy cells, reducing some of the harsh side effects associated with traditional cancer treatments. Furthermore, this personalized treatment could provide new hope for patients who have relapsed after standard therapies.

What evidence suggests that this trial's treatments could be effective for leukemia and lymphoma?

Research has shown that CD19-directed CAR T-cell therapies yield promising results for treating certain blood cancers, such as leukemia and lymphoma. In this trial, participants will receive CD19CAR/virus-specific T cells at varying dose levels, based on their group assignment. Studies confirm these therapies can benefit patients with relapsed or hard-to-treat B-cell lymphoma, with significant effects in some cases. Specifically, some trials found that 21% to 29% of patients with chronic lymphocytic leukemia experienced complete remission, meaning the cancer was no longer detectable. Long-term follow-ups revealed that 44% of younger patients had event-free survival (time without cancer returning) and 63% had overall survival (time they lived) at three years. These findings suggest that CD19 CAR T-cells could be a hopeful treatment option for individuals with certain blood and lymph node cancers. ^{1 2 6 7 8}

Who Is on the Research Team?

Carlos Ramos, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for patients of any age and sex with CD19+ B-ALL or B-CLL/NHL undergoing a bone marrow transplant. They must have a life expectancy of at least 6 weeks, be able to consent, and use effective birth control post-treatment. Excluded are those with severe allergies to murine proteins, active GVHD above grade II, pregnancy, lactation, or severe infections.

Inclusion Criteria

I (or my guardian) can understand and agree to the study's terms.

Patients should have been off other investigational antiviral or antitumor therapy for one month prior to entry in this study

Patients with life expectancy greater than or equal to 6 weeks

Exclusion Criteria

Pregnant or lactating

History of hypersensitivity reactions to murine protein-containing products

I am currently on corticosteroids for graft-versus-host disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of CD19 chimeric receptor trivirus specific T cells post-HSCT, with potential for up to 6 additional doses if stable disease or partial response is observed

6 weeks

1 visit (in-person) for initial dose, additional visits for further doses if applicable

Follow-up

Participants are monitored for safety, effectiveness, and long-term side effects of gene transfer

15 years

What Are the Treatments Tested in This Trial?

Interventions

• CD19CAR/virus specific T cells

Trial Overview

The study tests T cells modified with an anti-CD19 chimeric receptor (CD19CAR) against leukemia/lymphoma post-transplant. It aims to find the highest safe dose of these T cells while assessing side effects and their longevity in preventing relapse and infections.

How Is the Trial Designed?

Group I: Group B without disease Experimental Treatment 2 Interventions

CD19+ B cell CLL or NHL undergoing allogeneic HSCT, without detectable disease post-HSCT Patients will receive CD19CAR/virus specific T cells - Dose Level 1: 1.5 x 10\^7/m2 Patients will be evaluated in the clinic and a single dose of CTL will be administered from day +30 post-HSCT. Patients may be premedicated with Benadryl and Tylenol before receiving the injection of cells.

Group II: Group B with disease Experimental Treatment 2 Interventions

CD19+ B cell CLL or NHL undergoing allogeneic HSCT, with minimal residual disease or relapse post-HSCT Patients will receive one of the following dose levels of CD19CAR/virus specific T cells: Dose Level 1: 1.5 x 10\^7/m2 Dose Level 2: 4.5 x 10\^7/m2 Dose Level 3: 1.2 x 10\^8/m2 Patients will be evaluated in the clinic and a single dose of CTL will be administered from day +30 post-HSCT. Patients may be premedicated with Benadryl and Tylenol before receiving the injection of cells. If patients with relapse have a partial response or have stable disease they will be eligible to receive up to 6 further doses of CTLs, each of which will consist of the same number or less than as their first injection.

Group III: Group A without disease Experimental Treatment 2 Interventions

CD19+ B-ALL undergoing allogeneic HSCT, without detectable disease post-HSCT. Patients will receive CD19CAR/virus specific T cells - Dose Level 1: 1.5 x 10\^7/m2 Patients will be evaluated in the clinic and a single dose of CTL will be administered from day +30 post-HSCT. Patients may be premedicated with Benadryl and Tylenol before receiving the injection of cells.

Group IV: Group A with disease Experimental Treatment 2 Interventions

CD19+ B-ALL undergoing allogeneic HSCT, with minimal residual disease or relapse post-HSCT Patients will receive one of the following dose levels of CD19CAR/virus specific T cells: Dose Level 1: 1.5 x 10\^7/m2 Dose Level 2: 4.5 x 10\^7/m2 Dose Level 3: 1.2 x 10\^8/m2 Patients will be evaluated in the clinic and a single dose of CTL will be administered from day +30 post-HSCT. Patients may be premedicated with Benadryl and Tylenol before receiving the injection of cells. If patients with relapse have a partial response or have stable disease they will be eligible to receive up to 6 further doses of CTLs, each of which will consist of the same number or less than as their first injection.

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Published Research Related to This Trial

Two patients who received CD19-targeted CAR T cell therapy developed lymphoma, highlighting a potential safety concern associated with this treatment.

This case raises important questions about the long-term effects and monitoring of patients undergoing CAR T cell therapy, particularly regarding the risk of secondary malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unforeseen Development of Lymphoma Derived from piggyBac CAR T Cells. [2021]

Adoptive cellular therapy using CD19 CAR T cells has shown remarkable efficacy in achieving remission in 67-90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), indicating a promising treatment option for this high-risk group.

While CD19 CAR T-cell therapy can lead to significant toxicities such as cytokine release syndrome and neurologic dysfunction, these effects are generally manageable with supportive care, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-redirected chimeric antigen receptor-modified T cells: a promising immunotherapy for children and adults with B-cell acute lymphoblastic leukemia (ALL). Tasian, SK., Gardner, RA.[2020]

In a study of 50 patients receiving CD19 CAR-T cell therapy, 36% experienced infectious complications, with a median time to infection of 225 days, indicating that infections can occur well after treatment.

Severe infections were common, with 54.8% leading to significant health issues, including hospitalization and even death in 6% of patients, highlighting the need for ongoing monitoring and improved antimicrobial prophylaxis strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infectious complications among CD19 CAR-T cell therapy recipients: A single-center experience. Walker, B., Zimmer, AJ., Stohs, EJ., et al.[2023]

Anti-CD19 CAR T-cell therapy has shown remarkable efficacy in treating relapsed or refractory aggressive B-cell lymphomas, leading to durable remissions in patients who previously had no effective treatment options.

Three CAR T-cell therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) are approved for use, each differing in their design, manufacturing processes, and safety profiles, highlighting the need for personalized approaches in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 CAR T-Cell Therapy for B-Cell Non-Hodgkin Lymphoma. Abramson, JS.[2021]

CAR T cell therapy targeting CD19 has shown remarkable efficacy, achieving complete remission in up to 90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), compared to a 30% response rate with traditional chemotherapy.

The therapy involves genetically modifying T cells to express a chimeric antigen receptor, allowing them to effectively target and eliminate cancer cells, although it is important to note that there are unique toxicities associated with this treatment that require careful management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-Targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B-cell acute lymphoblastic leukemia. Davila, ML., Brentjens, RJ.[2023]

CD19 is a highly effective target for CAR T-cell therapies, showing significant responses in patients with relapsed B-cell malignancies, particularly chronic lymphocytic leukemia and acute lymphoblastic leukemia.

While treatment with CD19-CAR T cells can lead to severe systemic inflammatory reactions, these are generally reversible with proper medical care, highlighting the importance of monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-CAR trials. Ramos, CA., Savoldo, B., Dotti, G.[2022]

CAR-T cell therapy has shown significant success in treating CD19-positive B-cell cancers, but this review explores its potential in other blood cancers, particularly Hodgkin's lymphoma and acute myeloid leukemia.

The focus on hematologic malignancies beyond CD19 highlights the expanding applications of CAR-T cell technology, suggesting it may be effective for a broader range of blood cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T cells beyond CD19, UnCAR-Ted territory. Leick, MB., Maus, MV.[2020]

CAR T-cells are engineered T-cells that target the CD19 antigen, showing promising initial results in treating various B-cell malignancies, including acute lymphocytic leukaemia and chronic lymphocytic leukaemia.

While the treatment shows potential, there are significant differences in patient responses and notable side effects that require careful management, highlighting the need for personalized approaches in therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. Heijink, DM., Kater, AP., Hazenberg, MD., et al.[2017]

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