CD19 CAR-T Cells for Leukemia and Lymphoma

(MULTIPRAT Trial)

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

68 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment CD19 CAR-T Cells for Leukemia and Lymphoma?

CD19 CAR-T cells have shown remarkable results, inducing complete remissions in up to 90% of patients with relapsed or chemotherapy-resistant B-cell acute lymphoblastic leukemia, a type of blood cancer. This is a significant improvement compared to the 30% response rate expected with traditional chemotherapy. ^{1 2 3 4 5}

Is CD19 CAR-T cell therapy safe for humans?

CD19 CAR-T cell therapy can cause serious side effects like cytokine release syndrome (a severe immune reaction) and neurological issues, but these are generally manageable with supportive care. Some patients may experience infections or other complications, but ongoing research is focused on improving safety measures. ^{2 6 7 8 9}

How is the CD19 CAR-T cell treatment different from other treatments for leukemia and lymphoma?

CD19 CAR-T cell treatment is unique because it uses genetically modified T cells to specifically target and attack cancer cells expressing the CD19 protein, which is common in B-cell leukemias and lymphomas. This approach can lead to high remission rates in patients who do not respond to traditional chemotherapy, making it a promising option for difficult-to-treat cases. ^{1 2 3 4 10}

What is the purpose of this trial?

Subjects are having a bone marrow or SCT for either a type of cancer of the blood called Leukemia or a cancer of the lymph nodes called non- Hodgkin's Lymphoma. Although a transplant can cure leukemia or lymphoma, some people will relapse. In those who relapse, current treatment cures only a very small percentage. Although giving patients a dose of donor immune cells before relapse can prevent relapse of the leukemia or lymphoma, DLI can also cause a serious complication called graft versus host disease (GVHD). This is a gene transfer research study using special immune cells which are specific for these cancer cells. The body has different ways of fighting infection and disease. This study combines 2 of those ways, antibodies and T cells. T cells (CTLs or cytotoxic T cells) are infection-fighting blood cells that can kill cells, including tumor cells. Antibodies and T cells have been used to treat patients with cancers; they have shown promise, but haven't been strong enough to cure most patients. The antibody used in this study is called anti-CD19. This antibody sticks to leukemia cells because of a substance on the outside of these cells called CD19. For this study, the anti-CD19 antibody has been changed so that instead of floating free in the blood it is now joined to T cells. When an antibody is joined to a T cell in this way it's called a chimeric receptor. In the laboratory, investigators found that T cells that are trained to recognize common viruses can stay in the blood stream for many years. By joining the anti-CD19 antibody to CTLs that recognize viruses, they believe that they will also be able to make a cell that can last a long time in the body, provide protection from viruses, and recognize and kill leukemia. The CTLs which we will join the anti-CD19 antibody to attack 3 viruses (trivirus-specific CTLs), CMV, EBV, and adenovirus. Studies have shown that trivirus-specific CTLs grown from the stem cell donor can be given safely to transplant recipients and can stop these viruses from causing severe infections. These CD19 chimeric receptor trivirus specific T cells are an investigational product not approved by the FDA. The purpose of this study is to find the biggest dose of chimeric T cells that is safe, to assess the side effects, to see how long the T cells last and to evaluate whether this therapy might help prevent infections and relapse in people with CD19+ leukemia or lymphoma having a SCT.

Research Team

Carlos Ramos, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

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

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

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. [2017]

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

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

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

CAR-T cells beyond CD19, UnCAR-Ted territory. [2020]

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

CD19-CAR trials. [2022]

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

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

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

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

7. England 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). [2020]

8. Denmark pubmed.ncbi.nlm.nih.gov

Infectious complications among CD19 CAR-T cell therapy recipients: A single-center experience. [2023]

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

CD19 chimeric antigen receptor T cell therapy in leukemia xenograft mouse: Anti-leukemic efficacy, kinetics, and 4-week single-dose toxicity. [2023]

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

In Search of an Ideal CAR-T Cell Antigen Target. [2022]