TAA-Specific Cytotoxic T-Lymphocytes for Multiple Myeloma

(TACTAM Trial)

Recruiting at 2 trial locations

Overseen By Premal Lulla, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must be taking: Lenalidomide, Thalidomide, Pomalidomide, Checkpoint inhibitors

Must not be taking: Systemic corticosteroids

Disqualifiers: Severe infection, Active HIV, Pregnant, others

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

Compensation: Varies

Number of Visits: 14

Duration: 8-32 weeks

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new therapy that uses the body's own immune cells, called TAA-specific CTLs (Tumor-Associated Antigen-Specific Cytotoxic T-Lymphocytes), to target proteins on cancer cells in multiple myeloma and related conditions. The trial aims to find the safest dose, understand potential side effects, and determine if this therapy can help manage these conditions. It is open to patients with high-risk monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma, or multiple myeloma who have already tried one treatment. 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.

Do I need to stop my current medications for the trial?

You need to stop any investigational therapy for one month and conventional therapy for at least 48 hours before joining the study, except for certain medications like lenalidomide, thalidomide, pomalidomide, or immune checkpoint inhibitors.

Is there any evidence suggesting that TAA-specific CTLs are likely to be safe for humans?

Research has shown that a type of immune cell treatment, called TAA-specific CTLs, has been tested in patients with conditions similar to multiple myeloma. In these studies, the treatment was generally safe. It targets proteins on cancer cells, potentially sparing normal cells and reducing unwanted side effects.

Reports from these studies indicate that patients tolerated the treatment well, with few serious side effects and mostly mild reactions. This suggests that TAA-specific CTLs could be a safe option for patients with multiple myeloma or related conditions like MGUS and smoldering myeloma. However, as this is a new therapy, further research is needed to confirm its long-term safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Researchers are excited about TAA-specific cytotoxic T-lymphocytes (CTLs) for multiple myeloma because they offer a targeted approach that differs from the typical treatments like chemotherapy, immunomodulatory drugs, and proteasome inhibitors. Unlike these standard options that broadly attack cancer cells and sometimes healthy cells, TAA-specific CTLs are engineered to recognize and kill cancer cells by targeting tumor-associated antigens (TAAs) unique to myeloma. This precision potentially leads to fewer side effects and more effective outcomes. Additionally, for patients with high-risk MGUS or smoldering myeloma, TAA-specific CTLs might provide a proactive treatment strategy, which is not typically available with current standard care.

What evidence suggests that TAA-specific CTLs might be an effective treatment for multiple myeloma?

Research suggests that a specific type of immune cell, known as TAA-specific cytotoxic T lymphocytes (CTLs), could be a promising treatment for multiple myeloma and similar conditions. In this trial, participants will be divided into different groups to receive TAA-specific CTLs. Earlier studies showed that patients with multiple myeloma who received these special immune cells had a stronger immune response against their cancer. These T cells target proteins primarily found on cancer cells, aiming to destroy them. Other research has shown that using several small protein pieces can enhance immune responses against tumors. While these findings are encouraging, more research is needed to confirm the effectiveness of this treatment for multiple myeloma. ^{1 3 6 7 8}

Who Is on the Research Team?

Premal Lulla, MD

Principal Investigator

Baylor College of Medicine/Houston Methodist Hospital

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Multiple Myeloma, high-risk MGUS, or smoldering myeloma. Participants must have had at least one prior treatment if they have Multiple Myeloma and should expect to live more than six weeks. They need a certain level of blood oxygen, liver function, and kidney function to join. Pregnant women can't participate; others must use effective birth control.

Inclusion Criteria

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

I am 18 or older with high risk MGUS or smoldering myeloma.

I am 18 or older with high risk MGUS/smoldering myeloma or have multiple myeloma and received treatment.

Exclusion Criteria

You have an ongoing HIV infection at the time of blood collection.

I am currently suffering from a severe infection.

I have taken corticosteroids within 2 days before receiving a CTL infusion.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive TAA-specific CTLs with initial two doses given two weeks apart, followed by up to six additional doses at monthly intervals if disease is stable or decreased

8-32 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with blood tests and imaging studies conducted at specified intervals

1 year

Regular visits (in-person) and annual contact for up to 5 years

Long-term follow-up

Participants are contacted annually to evaluate disease response long-term

4 additional years

What Are the Treatments Tested in This Trial?

Interventions

• TAA-specific CTLs

Trial Overview The study tests TAA-specific CTLs (immune cells) against five cancer cell proteins in patients with multiple myeloma or related conditions. The goal is to find the highest safe dose of these cells, understand side effects, and see if this therapy helps prevent disease progression.

How Is the Trial Designed?

Group I: Group C Experimental Treatment 1 Intervention

Patients with high risk MGUS or smoldering myeloma receiving a fixed dose TAA-Specific CTLs

Group II: Group B Experimental Treatment 1 Intervention

Patients receiving TAA-Specific CTLs as adjunctive therapy following autologous or syngeneic transplant for myeloma

Group III: Group A Experimental Treatment 1 Intervention

Patients receiving TAA-specific CTLs as therapy for Myeloma

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Harris County Hospital District

Collaborator

Trials

7

Recruited

410+

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+

Published Research Related to This Trial

Hybrid cell lines created from EBV B-lymphoblastoid cells and myeloma cells successfully stimulated the production of antigen-specific, cytotoxic T-lymphocytes in peripheral blood lymphocytes from multiple myeloma patients, indicating a potential new approach for immunotherapy.

This study highlights that these hybrid cell lines can effectively target tumor-associated antigens (TAAs) like hTERT, MUC1, MAGE-C1, and CS1, which are commonly expressed in multiple myeloma, suggesting they could enhance the effectiveness of adoptive immunotherapy for this challenging cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro Generation of Cytotoxic T Cells With Potential for Adoptive Tumor Immunotherapy of Multiple Myeloma. Khalaf, WS., Garg, M., Mohamed, YS., et al.[2020]

Cytotoxic T lymphocytes (CTLs) play a crucial role in fighting cancer by recognizing tumor-specific antigens, which are presented by cells in the body.

The review discusses the development of peptide-based vaccines that target these tumor-associated antigens, highlighting their potential to enhance the immune response against cancer and improve CTL therapy in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Tumor antigen-specific cytotoxic T lymphocytes and cancer immunotherapy - review]. Liu, Y.[2016]

A new method has been developed to generate cytotoxic T lymphocytes (CTLs) that can target a variety of nonviral tumor-associated antigens in Hodgkin and non-Hodgkin lymphoma, potentially expanding treatment options for EBV-negative tumors.

This approach successfully produced CTLs from all nine healthy donors and five out of eight lymphoma patients, demonstrating its effectiveness across different human leukocyte antigen (HLA) types and suggesting a promising avenue for immunotherapy in a broader range of lymphoma cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytotoxic T lymphocytes simultaneously targeting multiple tumor-associated antigens to treat EBV negative lymphoma. Gerdemann, U., Katari, U., Christin, AS., et al.[2021]

In a study involving 12 chronic lymphocytic leukemia (CLL) patients, MDM2-specific T cells were successfully generated in 7 patients, demonstrating the potential of MDM2 as a tumor-associated antigen for immunotherapy.

The study found that the ability of antigen-presenting cells (APCs) to secrete IFN-gamma was a key factor in generating effective MDM2-specific T cells, highlighting the importance of APC functionality in developing targeted immune responses against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MDM2 is recognized as a tumor-associated antigen in chronic lymphocytic leukemia by CD8+ autologous T lymphocytes. Mayr, C., Bund, D., Schlee, M., et al.[2020]

Tumor-associated antigen-specific cytotoxic T lymphocytes (TAA-CTL) were safely generated and infused into patients with multiple myeloma and non-Hodgkin lymphoma, with no significant adverse reactions reported during the treatment.

In a small group of 7 patients, TAA-CTL therapy showed promising efficacy, as 5 patients experienced positive clinical effects, and an increase in specific immune responses was observed 2-3 weeks post-infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Research of Dendritic Cell-Mediated Tumor-Associated Antigen-Specific Cytotoxic T Lymphocytes in the Treatment of Multiple Myeloma and Non-Hodgkin Lymphoma]. Li, XH., Xue, L., Xu, H., et al.[2020]

This study successfully identified and expanded myeloma-specific precursor cytotoxic T cells (pCTL) from a patient with multiple myeloma in complete remission, demonstrating a novel approach to targeting cancer cells.

The isolated CD8+ cytotoxic T-cell clone (CT5) showed specific recognition and cytotoxicity against the patient's myeloma cells while sparing other healthy cells, indicating a potential for targeted immunotherapy in multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation of human lymphocyte antigens class I-restricted cytotoxic T lymphocytes against autologous myeloma cells. Pellat-Deceunynck, C., Jego, G., Harousseau, JL., et al.[2006]

Myeloma cells are more susceptible to destruction by WT1-specific cytotoxic T lymphocytes (CTLs) compared to lymphoma cells, despite similar levels of WT1 expression, indicating a unique sensitivity in myeloma cells.

The study suggests that the effectiveness of CTL-mediated cytotoxicity is influenced by the extent of membrane damage caused by perforin, making WT1 a promising target for immunotherapy in multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myeloma cells are highly sensitive to the granule exocytosis pathway mediated by WT1-specific cytotoxic T lymphocytes. Azuma, T., Otsuki, T., Kuzushima, K., et al.[2013]

An autologous T cell therapy targeting multiple tumor-associated antigens (mTAAs) was tested in 21 patients with high-risk, relapsed or refractory multiple myeloma, showing good tolerance with only two cases of transient grade III adverse events.

Patients receiving this therapy experienced longer than expected progression-free survival, with some achieving objective responses, indicating that this approach may provide a promising long-term benefit for difficult-to-treat multiple myeloma cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and clinical effects of administering a multiantigen-targeted T cell therapy to patients with multiple myeloma. Lulla, PD., Tzannou, I., Vasileiou, S., et al.[2021]

In a first-in-human trial involving 15 patients with relapsed or refractory solid tumors, tumor-associated antigen cytotoxic T cells (TAA-Ts) were administered safely without any dose-limiting toxicities, demonstrating a promising new therapeutic approach.

Of the evaluable patients, 73% showed stable disease or better at day 45 post-infusion, with 6 patients remaining progression-free for a median of 13.9 months, indicating that TAA-Ts can effectively stabilize disease and prolong time to progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy of Relapsed and Refractory Solid Tumors With Ex Vivo Expanded Multi-Tumor Associated Antigen Specific Cytotoxic T Lymphocytes: A Phase I Study. Hont, AB., Cruz, CR., Ulrey, R., et al.[2020]

Citations

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Tumor-Associated Antigen-Specific Cytotoxic T ... This study is for patients that have a cancer called Multiple Myeloma, monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SM).

2. clinicaltrial.be clinicaltrial.be/en/details/74518?per_page=100&recruiting=1&enrolling_by_invitation=0&active_not_recruiting=0&not_yet_recruiting=0&completed=0&only_recruiting=1&only_eligible=0

Tumor-Associated Antigen-Specific Cytotoxic T- ... ... TAA-specific CTLs. This dose Was determined based on data obtained from patients who have multiple myeloma and have received these cells.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02291848?tab=history&a=1

Record History | ver. 1: 2014-11-12 | NCT02291848 A phase of research to describe clinical trials that gather more information about a drug's safety and effectiveness by studying different populations and ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3839582/

Myeloma-specific multiple peptides able to generate ... The efficacy of peptide vaccines may be enhanced by stimulating immune cells with multiple peptides derived from distinct tumor-associated antigens.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2018.36.5_suppl.218

T cell responses to tumor associated antigens in multiple ... Conclusions: Our data suggests oncolytic measles virotherapy boosted the cytotoxic T lymphocyte response against tumor associated antigens in ...

6. trialx.com trialx.com/clinical-trials/listings/225581/tumor-associated-antigen-specific-cytotoxic-t-lymphocytes-for-multiple-myeloma/

Tumor-Associated Antigen-Specific Cytotoxic T ... This study is for patients that have a cancer called Multiple Myeloma, monoclonal gammopathy of undetermined significance (MGUS) or smoldering ...

7. ctsearchsupport.org ctsearchsupport.org/clinical-trials/tumor-associated-antigen-specific-cytotoxic-t-lymphocytes-for-multiple-myeloma

Tumor-associated antigen (TAA) cytotoxic T lymphocytes ... To find out:The highest dose of TAA CTLs that is safe to giveIf TAA CTLs are safe and work well to treat multiple myeloma.

8. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/50/NCT03093350/Prot_SAP_000.pdf

TUMOR-ASSOCIATED ANTIGEN (TAA)-SPECIFIC ... TUMOR-ASSOCIATED ANTIGEN (TAA)-SPECIFIC CYTOTOXIC T LYMPHOCYTES. ADMINISTERED IN PATIENTS WITH BREAST CANCER (TACTIC). PRINCIPAL INVESTIGATORS. Ann M. Leen ...