Geriatric Assessments and Interventions for Lymphoma and Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Disqualifiers: Prior CAR-T therapy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 102

Duration: 30 days post-CAR-T infusion

164 Participants Needed

Trial Summary

What is the purpose of this trial?

This clinical trial compares the effectiveness of geriatric assessment (GA) guided interventions to accelerate functional recovery after chimeric antigen receptor T-cell (CAR-T) therapy compared to standard of care (SOC) in patients 60 years and older with B-cell non-Hodgkin lymphoma (NHL) or multiple myeloma (MM). A large number of patients diagnosed with cancer are over the age of 60, yet most cancer treatments are developed for younger patients. Therefore, older patients may be less likely to be offered stronger treatments, such as CAR-T therapy, due to possible side effects. Geriatric assessment is a multi-dimensional health assessment tool combining patient reported and objective measures covering physical function, mental processes (cognitive), and nutrition. Pre-treatment assessments may identify weaknesses in older adults and may guide interventions for physical therapy, cognitive changes and nutrition to decrease CAR-T therapy side effects and improve care in older adults with NHL or MM.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the treatment CAR-T Therapy for lymphoma and multiple myeloma?

Research shows that CAR-T therapies like Tisagenlecleucel and Axicabtagene ciloleucel are highly effective in treating certain types of B-cell leukemia and lymphoma, which are similar to the conditions being studied in this trial. These therapies have been approved for use in relapsed or refractory cases, indicating their potential effectiveness. ^{1 2 3 4 5}

Is CAR-T cell therapy safe for humans?

CAR-T cell therapies, like axicabtagene ciloleucel and tisagenlecleucel, have been approved for use and have shown good results, but they can also cause side effects. Managing these side effects is important, and ongoing research aims to reduce them in the future. ^{1 6 7 8 9}

How is CAR-T therapy different from other treatments for lymphoma and multiple myeloma?

CAR-T therapy is unique because it involves modifying a patient's own T-cells (a type of immune cell) to better recognize and attack cancer cells, which is different from traditional treatments like chemotherapy that target cancer cells directly. This personalized approach can be particularly effective for patients with relapsed or refractory lymphoma and multiple myeloma, offering a new option when other treatments have failed. ^{1 4 8 10 11}

Research Team

Andrew S. Artz

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for people aged 60 or older with B-cell non-Hodgkin lymphoma or multiple myeloma who are about to receive FDA-approved CAR-T therapy. They must understand English or Spanish, be able to consent, and their doctor must agree they can join. Those who've had prior CAR-T therapy or have conditions that make the study unsafe cannot participate.

Inclusion Criteria

I can attend at least one visit before starting my intensive treatment preparation.

Ability to provide informed consent

Patient's physician must agree for patient participation. A physician may elect to provide blanket agreement for participation of any eligible CAR-T patient under their care

Exclusion Criteria

Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Any condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures

I have previously received CAR-T therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment Optimization

Geriatric assessment and trimodality optimization including physical therapy, cognitive education, and nutritional guidance before lymphodepleting chemotherapy

Up to start of lymphodepletion

Multiple visits for optimization activities

Treatment

Patients receive CAR-T therapy with ongoing interventions based on geriatric assessment

30 days post-CAR-T infusion

At least 2 times a week while inpatient, and at least once every other week outpatient

Follow-up

Participants are monitored for safety, effectiveness, and quality of life after treatment

Up to 1 year

Follow-up at day 100 and then up to 1 year

Treatment Details

Interventions

• CAR-T Therapy
• Cognitive Intervention
• Comprehensive Geriatric Assessment
• Nutritional Intervention
• Physical Therapy
• Questionnaire Administration

Trial Overview The GOCART Study tests if special assessments and interventions based on geriatric health (covering physical function, cognition, nutrition) can help older adults recover faster after CAR-T therapy compared to standard care. It aims to tailor treatments better suited for patients' age-related needs.

Participant Groups

Group I: Arm I (PT, cognitive education, nutrition education) Experimental Treatment 5 Interventions

Patients undergo GA before lymphodepleting chemotherapy and recommendations based on assessment results communicated to treating physicians. Patients receive PT and delirium prevention education prior to lymphodepletion, at least once before CAR-T therapy, at least 2 times a week while inpatient, and at least once every other week outpatient up to day 30. Additionally, patients receive personalized nutritional guidance from a registered dietician prior to lymphodepletion, prior to CAR-T therapy and at least once a week up to day 30.

Group II: Arm II (standard of care) Active Control 2 Interventions

Patients undergo GA and receive standard of care throughout study.

CAR-T Therapy is already approved in United States, European Union for the following indications:

Approved in United States as Kymriah for:

• B-cell precursor acute lymphoblastic leukemia (ALL)
• Relapsed or refractory large B-cell lymphoma
• Diffuse large B-cell lymphoma (DLBCL)

Approved in European Union as Kymriah for:

• B-cell precursor acute lymphoblastic leukemia (ALL)
• Relapsed or refractory large B-cell lymphoma
• Diffuse large B-cell lymphoma (DLBCL)

Approved in United States as Yescarta for:

• Relapsed or refractory large B-cell lymphoma
• Diffuse large B-cell lymphoma (DLBCL)

Approved in European Union as Yescarta for:

• Relapsed or refractory large B-cell lymphoma
• Diffuse large B-cell lymphoma (DLBCL)

Approved in United States as Tecartus for:

• Relapsed or refractory mantle cell lymphoma
• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL)

Approved in European Union as Tecartus for:

• Relapsed or refractory mantle cell lymphoma
• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL)

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

A survey of 41 experienced clinicians revealed that many do not consider a history of malignancy or prior treatments as contraindications for CAR T-cell therapy, indicating a broader eligibility for patients than previously thought.

There is significant variability in follow-up care models after CAR T therapy, with most clinicians recommending frequent hospital visits in the initial month, highlighting the need for standardized guidelines in patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An international survey on the management of patients receiving CAR T-cell therapy for haematological malignancies on behalf of the Chronic Malignancies Working Party of EBMT. Hayden, PJ., Sirait, T., Koster, L., et al.[2021]

Tisagenlecleucel and axicabtagene ciloleucel are groundbreaking CAR-T cell therapies that have shown high effectiveness in treating relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) and certain types of B-cell non-Hodgkin lymphomas.

This review highlights the challenges faced by physicians in administering these therapies and discusses future directions for research and treatment in the field of immune and cellular therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19 chimeric antigen receptor-T cells in B-cell leukemia and lymphoma: current status and perspectives. Mohty, M., Gautier, J., Malard, F., et al.[2022]

CAR T cell therapy, specifically with tisagenlecleucel and axicabtagene ciloleucel, has been authorized in Europe for treating certain types of blood cancers, showing efficacy in relapsed/refractory acute lymphoblastic leukemia and diffuse large B-cell lymphoma.

The recommendations provided focus on managing medium-term complications like cytopenias and B-cell aplasia, emphasizing the importance of supportive care for patients undergoing this innovative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Medium-term follow-up of patients treated with chimeric antigen receptor T cells (CAR T cells): Recommendations of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. Alsuliman, T., Drieu La Rochelle, L., Campidelli, A., et al.[2022]

In a study of 72 adult patients with relapsed or refractory non-Hodgkin lymphoma treated with tisagenlecleucel, 94.4% received the therapy in an outpatient setting, demonstrating that this approach is both safe and feasible.

The overall response rate was 43%, with a complete response in 34.7% of patients, and serious adverse events like grade 3-4 cytokine release syndrome were not observed, indicating a manageable safety profile for outpatient CAR T therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Tisagenlecleucel in Lymphoma Patients With Predominant Management in an Ambulatory Setting. Nasta, SD., Hughes, ME., Namoglu, EC., et al.[2022]

CAR T-cell therapies, such as tisagenlecleucel (Kymriah™) and axicabtagene ciloleucel (Yescarta™), are effective treatments for relapsed/refractory B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma, utilizing genetically modified T cells that target the CD19 antigen.

These therapies are classified as 'living drugs' because they involve the genetic engineering of a patient's own T cells, highlighting the importance of proper collection and manufacturing processes for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[How to perform leukapheresis for procurement of the staring material used for commercial CAR T-cell manufacturing: A consensus from experts convened by the SFGM-TC]. Carnoy, S., Beaumont, JL., Kanouni, T., et al.[2021]

CAR-T cell therapies, specifically axicabtagene ciloleucel and tisagenlecleucel, have significantly improved outcomes for patients with relapsed or refractory aggressive B-cell lymphomas, with approvals based on pivotal trials demonstrating their efficacy after multiple prior treatments.

Despite their similar CAR technologies, differences in manufacturing and clinical trial designs exist between these therapies, highlighting the need for ongoing monitoring of patient responses and potential long-term side effects in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials. Westin, JR., Kersten, MJ., Salles, G., et al.[2022]

Cytokine release syndrome (CRS) is the most common adverse reaction reported after CAR-T therapy, with significantly higher reports for axicabtagene ciloleucel compared to tisagenlecleucel, indicating a need for careful monitoring of this side effect.

The study analyzed 1426 reports of adverse drug reactions from real clinical settings, supporting the overall safety profile of CAR-T therapies while confirming CRS as a major concern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of chimeric antigen receptor T-cell immunotherapies (CAR-T) in clinical practice. Bonaldo, G., Montanaro, N., AlbertoVaccheri, ., et al.[2021]

Two CAR T cell therapies, Tisagenlecleucel and Axicabtagene ciloleucel, have been approved for treating specific types of blood cancers, including B-cell acute lymphoblastic leukemia and large B-cell lymphoma, in patients who have not responded to other treatments.

This review emphasizes the importance of recognizing and managing the toxicities associated with CAR T cell therapies, while also suggesting future strategies to reduce these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cell Toxicity: Current Management and Future Directions. Yáñez, L., Sánchez-Escamilla, M., Perales, MA.[2020]

Chimeric antigen receptor (CAR) T-cell therapy, such as tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta), is an effective treatment for relapsed/refractory B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma, utilizing genetically modified T-cells that target the CD19 antigen.

This collaborative work provides practical guidance for healthcare centers on how to select patients for these commercially available CAR T-cell therapies, ensuring appropriate use and maximizing treatment benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Eligibility of patients for CAR T-cell: Expert opinion-based collaborative work by the SFGM-TC]. Beauvais, D., Bachy, E., Baruchel, A., et al.[2021]

In a study involving 82 patients (41 elderly aged 70+ and 41 younger), CAR-T cell therapy showed comparable efficacy and safety profiles between elderly and younger patients with relapsed/refractory diffuse large B-cell lymphoma, with no significant differences in severe side effects or response rates.

Despite similar treatment outcomes, elderly patients experienced worsening disability and cancer-related symptoms post-therapy, highlighting the need for longer rehabilitation to address these issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity and efficacy of chimeric antigen receptor T-cell therapy in patients with diffuse large B-cell lymphoma above the age of 70 years compared to younger patients - a matched control multicenter cohort study. Ram, R., Grisariu, S., Shargian-Alon, L., et al.[2022]

Anti-BCMA CAR-T therapy shows a high overall response rate of 93% in older adults (≥65 years) with relapsed/refractory multiple myeloma, which is comparable to the 86% response rate in younger patients, based on a systematic review of 14 studies involving 558 patients.

While older adults experience similar efficacy to younger patients, they have higher rates of immune cell-effector-associated neurotoxicity syndrome (ICANS) at 15%, indicating a need for careful monitoring of neurotoxicity in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of anti-BCMA CAR-T cell therapy in older adults with multiple myeloma: A systematic review and meta-analysis. Akhtar, OS., Sheeba, BA., Azad, F., et al.[2023]

References

1. France pubmed.ncbi.nlm.nih.gov

An international survey on the management of patients receiving CAR T-cell therapy for haematological malignancies on behalf of the Chronic Malignancies Working Party of EBMT. [2021]

2. England pubmed.ncbi.nlm.nih.gov

CD19 chimeric antigen receptor-T cells in B-cell leukemia and lymphoma: current status and perspectives. [2022]

3. France pubmed.ncbi.nlm.nih.gov

[Medium-term follow-up of patients treated with chimeric antigen receptor T cells (CAR T cells): Recommendations of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. [2022]

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

Outcomes of Tisagenlecleucel in Lymphoma Patients With Predominant Management in an Ambulatory Setting. [2022]

5. France pubmed.ncbi.nlm.nih.gov

[How to perform leukapheresis for procurement of the staring material used for commercial CAR T-cell manufacturing: A consensus from experts convened by the SFGM-TC]. [2021]

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

Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Safety profile of chimeric antigen receptor T-cell immunotherapies (CAR-T) in clinical practice. [2021]

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

CAR T Cell Toxicity: Current Management and Future Directions. [2020]

9. France pubmed.ncbi.nlm.nih.gov

[Eligibility of patients for CAR T-cell: Expert opinion-based collaborative work by the SFGM-TC]. [2021]

10. Italy pubmed.ncbi.nlm.nih.gov

Toxicity and efficacy of chimeric antigen receptor T-cell therapy in patients with diffuse large B-cell lymphoma above the age of 70 years compared to younger patients - a matched control multicenter cohort study. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and efficacy of anti-BCMA CAR-T cell therapy in older adults with multiple myeloma: A systematic review and meta-analysis. [2023]