Stem Cell + CAR T-Cell Therapy for Blood Cancers

Overseen By Clinical Trial Recruitment Navigator

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Joshua Sasine, MD, PhD

Must not be taking: Corticosteroids, Immunosuppressive drugs

Disqualifiers: Uncontrolled infection, Cardiac disease, Seizure disorder, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 60 days

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The study is designed to examine the feasibility and safety of collecting autologous hematopoietic stem cells (HSCs) to be combined with CAR T-cell therapy for patients with relapsed/refractory (r/r) hematological disease. The study will evaluate feasibility of collecting the target dose of HSCs from at least 50% of enrolled patients. The study will assess safety based on incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in the first 60 days post CAR T dosing, and also through the collection of adverse events (AEs) and serious adverse events (SAEs) as well as the durability of response after treatment with HSCs with CAR T. The study follows an open-label, single-center and single non-randomized cohort design. 20 subjects with r/r hematological malignancies will be enrolled and treated to evaluate the feasibility and preliminary safety of collecting autologous HSCs and combining them with CAR T-cell therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking corticosteroids and other immunosuppressive drugs at doses of 5 mg/day or more of prednisone (a type of steroid) or equivalent. There is a washout period (time without taking certain medications) of 10 days before leukapheresis (a procedure to collect blood cells) and 10 days before receiving CAR T-cell therapy.

What data supports the effectiveness of the treatment Stem Cell + CAR T-Cell Therapy for Blood Cancers?

Research shows that CAR T-cell therapy, which is part of this treatment, has been effective in treating blood cancers like B-cell malignancies by targeting specific cancer cells. Studies have demonstrated that CAR T-cells can lead to long-term remission in patients with advanced blood cancers, even when other treatments have failed. ^{1 2 3 4 5}

Is Stem Cell + CAR T-Cell Therapy generally safe for humans?

CAR T-Cell therapy, including products like Kymriah, has shown promise in treating blood cancers but can cause serious side effects. Common issues include cytokine release syndrome (a severe immune reaction), neurological problems, and blood cell deficiencies. While these therapies are advancing, managing these side effects is crucial for safe treatment. ^{6 7 8 9 10}

What makes the Stem Cell + CAR T-Cell Therapy unique for blood cancers?

This treatment is unique because it combines autologous hematopoietic stem cells (patient's own stem cells) with CAR T-cell therapy, which uses modified T-cells to specifically target and attack cancer cells. This approach is particularly promising for patients with blood cancers where other treatments have failed, offering a personalized and powerful immunotherapy option. ^{1 3 11 12 13}

Research Team

Joshua Sasine, MD, PhD

Principal Investigator

Cedars-Sinai Medical Center

Eligibility Criteria

Adults aged 18-85 with certain blood cancers that have come back or haven't responded to treatment can join. They must be healthy enough for the procedure, not have had recent heart issues or transplants, and can't be pregnant or breastfeeding. Participants need to agree to birth control use and follow study procedures.

Inclusion Criteria

Women who can have children must take a pregnancy test before the study starts.

My condition worsened after the last treatment or didn't improve significantly.

It's been over 2 weeks or 5 half-lives since my last cancer treatment.

Exclusion Criteria

I currently have or might have an infection that isn't under control or needs IV drugs.

Any medical condition likely to interfere with assessment of feasibility or safety of study treatment

I have not received a live vaccine in the last 6 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Collection and Preparation

Collection of autologous hematopoietic stem cells (HSCs) to be combined with CAR T-cell therapy

Up to 10 days

Multiple visits for collection and preparation

Treatment

Participants receive CAR T-cell therapy and are monitored for safety, including incidence of CRS and ICANS

60 days

Regular monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment, including response rate and recovery assessments

52 weeks

Periodic follow-up visits

Long-term Follow-up

Assessment of progression-free survival (PFS) and overall survival (OS) for up to 3 years

Up to 3 years

Treatment Details

Interventions

• Autologous Hematopoietic Stem Cells with Chimeric Antigen Receptor (CAR) T-Cell Therapy

Trial Overview The trial is testing if it's possible and safe to collect a person's own stem cells and add them to CAR T-cell therapy in patients whose blood cancer has returned after treatment or hasn’t improved. It will track how well this works in 20 people over the first two months by looking at side effects like CRS and ICANS.

Participant Groups

Group I: CAR T Therapy with Autologous Hematopoietic Stem Cells (aHSCs) Experimental Treatment 1 Intervention

Autologous Hematopoietic Stem Cells with Chimeric Antigen Receptor (CAR) T-Cell Therapy is already approved in European Union, United States for the following indications:

Approved in European Union as Kymriah for:

• B-cell acute lymphoblastic leukemia (ALL) in patients up to 25 years of age
• Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy

Approved in United States as Kymriah for:

• B-cell acute lymphoblastic leukemia (ALL) in patients up to 25 years of age
• Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy
• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy

Who Is Running the Clinical Trial?

Joshua Sasine, MD, PhD

Lead Sponsor

Trials

1

Recruited

20+

Findings from Research

CD19-targeted CAR-T therapy shows a high efficacy in treating refractory B-cell malignancies, with a complete remission rate of 55% and a partial remission rate of 25% based on a meta-analysis of 19 studies involving 391 patients.

While the treatment is effective, it is associated with manageable side effects, including fever (62%), hypotension (22%), and acute renal failure (24%), with no reported deaths due to toxicity, indicating a need for improved safety strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive Immunotherapy for B-cell Malignancies Using CD19- Targeted Chimeric Antigen Receptor T-Cells: A Systematic Review of Efficacy and Safety. Hao, L., Li, T., Chang, LJ., et al.[2019]

Adoptive T-cell therapy (ACT) using chimeric antigen receptors (CARs) has shown promise in treating hematological malignancies, particularly B-cell cancers, by enhancing T-cell signaling and persistence.

Second and third generation CARs, which include various costimulatory molecules, have demonstrated improved antitumor activity in both laboratory and clinical settings, indicating their potential effectiveness in cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive T-cell therapy of B-cell malignancies: conventional and physiological chimeric antigen receptors. Liu, L., Sun, M., Wang, Z.[2020]

CAR T cell therapy has become an important treatment for certain blood cancers, with three types of anti-CD19 CAR-T cells already approved for use in the Czech Republic, and more trials underway for targeting other cancer-specific antigens.

While the management of CAR-T cell therapy has improved, including updated guidelines for early toxicity, long-term follow-up is essential due to potential late toxicities, highlighting the need for ongoing research to enhance efficacy and reduce side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical aspects of CAR-T cell therapy. Jana, M., Tomáš, J., Michal, K., et al.[2022]

Cellular therapies like autologous and allogeneic hematopoietic cell transplantation (HCT) and CAR T cell therapy have shown long-term remission in advanced blood cancers, with CAR T therapy offering a targeted approach against malignancies that is effective even in patients who do not respond to traditional chemotherapy.

While allogeneic HCT provides immune-mediated protection against cancer, it can also harm normal cells, whereas CAR T therapy allows for precise targeting of cancer cells without the need for matching donor cells, though both therapies come with unique toxicities and challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T Cell Therapy versus Hematopoietic Stem Cell Transplantation: An Evolving Perspective. Goldsmith, SR., Ghobadi, A., Dipersio, JF., et al.[2023]

Chimeric antigen receptor (CAR) T cell therapy is a promising treatment for hematological malignancies, as these genetically engineered T cells can specifically target and recognize tumor-associated antigens.

Current studies indicate that CAR-T cells are being explored for their efficacy in treating various blood cancers, including leukemia and lymphomas, although the review also emphasizes the importance of understanding potential adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell treatment in hematologic malignancies. Goker, H., Malkan, UY., Demiroglu, H., et al.[2017]

CAR-T cell therapy shows promise in treating relapsed or refractory malignancies, particularly in hematological cancers like acute B-cell lymphoblastic leukemia and B-cell lymphomas, with ongoing research into its application for solid tumors.

This systematic review aims to comprehensively assess the safety and efficacy of CAR-T cell therapy by analyzing various studies, focusing on outcomes such as complete response rates and adverse events, to better understand its potential risks and benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in patients with haematological and solid malignancies: protocol for a systematic review and meta-analysis. Grigor, EJM., Fergusson, DA., Haggar, F., et al.[2019]

CAR-T cell therapies are becoming important treatments for blood cancers, with four products already available on the market and over 500 ongoing trials worldwide.

CAR-NK cell therapies are emerging as promising alternatives to CAR-T therapies, potentially reducing side effects and allowing for the use of cells from different donors, which could improve treatment accessibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status and perspective of CAR-T and CAR-NK cell therapy trials in Germany. Albinger, N., Hartmann, J., Ullrich, E.[2023]

CAR T cells have shown significant clinical effectiveness in treating blood cancers, but their success in solid tumors has been less impressive, highlighting the need for further research in this area.

While CAR T cell therapy can lead to serious side effects like cytokine release syndrome and neurological toxicity, some theoretical risks have not yet been observed in clinical settings, emphasizing the importance of managing known toxicities for safe treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity and management in CAR T-cell therapy. Bonifant, CL., Jackson, HJ., Brentjens, RJ., et al.[2023]

CAR-T cell therapy shows significant efficacy in treating hematological malignancies, but it is associated with high rates of hematological toxicity, with 80% of patients experiencing any grade of neutropenia, 61% thrombocytopenia, and 68% anemia based on a meta-analysis of 52 studies involving 2004 patients.

Severe hematological toxicities (grade ≥3) were notably high, with 60% experiencing neutropenia, 33% thrombocytopenia, and 32% anemia, particularly in younger patients and those with a history of multiple prior therapies, highlighting the need for careful monitoring and intervention to prevent life-threatening complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects in hematologic malignancies treated with chimeric antigen receptor (CAR) T cell therapy: a systematic review and Meta-analysis. Luo, W., Li, C., Zhang, Y., et al.[2022]

CAR T-cell therapy has shown promising results in treating hematological malignancies, but it is associated with various toxicities, particularly cytopenias that can occur at different time frames: early (<30 days), short-term (30-90 days), and prolonged (>90 days).

Understanding the causes and management of cytopenias is crucial for patient care and resource utilization, highlighting the need for a clinical guide to address these hematological toxicities associated with CAR T-cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T-OPENIA: Chimeric antigen receptor T-cell therapy-associated cytopenias. Taneja, A., Jain, T.[2022]

CAR-T-cell therapy is an innovative treatment for patients with blood cancers, but it often leads to immune-mediated toxicities that can complicate patient care.

Effective management of these toxicities requires early intervention with supportive care and medications like tocilizumab or corticosteroids, along with the need for better biomarkers to identify at-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identifying and managing CAR T-cell-mediated toxicities: on behalf of an Italian CAR-T multidisciplinary team. Martino, M., Macheda, S., Aguglia, U., et al.[2022]

Chimeric antigen receptor-modified T cells (CAR-Ts) are a promising new treatment for hematological malignancies, showing powerful efficacy against tumor cells by targeting specific cancer-associated antigens.

The review discusses the CAR-T manufacturing process and highlights ongoing clinical trials for various blood cancers, including acute lymphoblastic leukemia and multiple myeloma, indicating a growing interest and development in this area of immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy for hematological malignancies: Current status and new insights in chimeric antigen receptor T cells. Allegra, A., Innao, V., Gerace, D., et al.[2018]

In a systematic review of 45 studies involving 3,591 patients, CAR T-cell therapy was associated with a high incidence of infections, with overall infection rates at 33.8% and severe infections at 16.2%.

Most infections were bacterial or viral, with respiratory tract infections being the most common, while invasive fungal infections were rare, and the infection-related mortality rate was low at 1.8%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of infection in patients with hematological malignancies receiving CAR T-cell therapy: systematic review and meta-analysis. Telli Dizman, G., Aguado, JM., Fernández-Ruiz, M.[2022]

References

1. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Adoptive Immunotherapy for B-cell Malignancies Using CD19- Targeted Chimeric Antigen Receptor T-Cells: A Systematic Review of Efficacy and Safety. [2019]

2. Ireland pubmed.ncbi.nlm.nih.gov

Adoptive T-cell therapy of B-cell malignancies: conventional and physiological chimeric antigen receptors. [2020]

3. Czech Republic pubmed.ncbi.nlm.nih.gov

Practical aspects of CAR-T cell therapy. [2022]

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

Chimeric Antigen Receptor T Cell Therapy versus Hematopoietic Stem Cell Transplantation: An Evolving Perspective. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell treatment in hematologic malignancies. [2017]

6. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in patients with haematological and solid malignancies: protocol for a systematic review and meta-analysis. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Current status and perspective of CAR-T and CAR-NK cell therapy trials in Germany. [2023]

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

Toxicity and management in CAR T-cell therapy. [2023]

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

Adverse effects in hematologic malignancies treated with chimeric antigen receptor (CAR) T cell therapy: a systematic review and Meta-analysis. [2022]

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

CAR-T-OPENIA: Chimeric antigen receptor T-cell therapy-associated cytopenias. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Identifying and managing CAR T-cell-mediated toxicities: on behalf of an Italian CAR-T multidisciplinary team. [2022]

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

Adoptive immunotherapy for hematological malignancies: Current status and new insights in chimeric antigen receptor T cells. [2018]

13. England pubmed.ncbi.nlm.nih.gov

Risk of infection in patients with hematological malignancies receiving CAR T-cell therapy: systematic review and meta-analysis. [2022]