NK Cell Therapy + Mogamulizumab for T-Cell Lymphoma/Leukemia

Overseen By Thomas Needham

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: John Reneau

Must not be taking: Immunosuppressants, Live-virus vaccines

Disqualifiers: Active CNS lymphoma, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for treating certain blood cancers, specifically cutaneous T-cell lymphoma and adult T-cell leukemia/lymphoma. It combines two treatments: natural killer cells, a type of immune cell, and mogamulizumab (Poteligeo), a drug that inhibits cancer cell growth. The trial aims to determine the optimal dose and evaluate the effectiveness of these treatments in combination. Individuals with these specific cancers that have recurred or not responded to previous treatments may be suitable candidates for this study. 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 new treatment approach.

Will I have to stop taking my current medications?

The trial requires that all cancer therapies, including radiation, topical steroids, and chemotherapy, be stopped at least 1 week or 3 half-lives before starting the study, except for certain corticosteroids. Participants can continue medications for other conditions if there is evidence of T-cell lymphoma progression while on these medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that mogamulizumab is generally well-tolerated in past studies. Some patients have experienced side effects, but these are often manageable. For instance, in one study, 60% of patients did not complete the full treatment, suggesting some challenges, though this does not necessarily indicate serious safety issues for everyone.

Regarding third-party natural killer (NK) cells, direct information on their safety is limited. However, NK cells have shown promise in fighting cancer due to their role in the immune system. As this is an early trial, more data is needed to confirm their tolerability.

This combination treatment is still under study to determine the best dose and understand any potential side effects. Participants should be aware that while mogamulizumab has a known safety profile, the combination with NK cells remains under investigation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for T-cell lymphoma/leukemia because it combines mogamulizumab, a monoclonal antibody, with infusions of third-party natural killer (NK) cells, which is a novel approach. Most standard treatments focus on chemotherapy and radiation, but this therapy uses NK cells to potentially enhance the body's ability to target and destroy cancer cells more effectively. Additionally, mogamulizumab specifically targets the CCR4 receptor on cancer cells, which is different from conventional therapies that don't target specific receptors. This combination not only aims to improve treatment efficacy but also promises a more targeted attack on cancer cells, potentially leading to better outcomes with fewer side effects.

What evidence suggests that this trial's treatments could be effective for T-cell lymphoma/leukemia?

In this trial, participants will receive a combination of treatments, including mogamulizumab and third-party natural killer cells. Research has shown that mogamulizumab, which targets specific cancer cells, effectively treats relapsed cutaneous T-cell lymphoma. Studies indicate that it can reduce cancer in the blood and skin, with 49.2% and 27.4% of patients experiencing improvements lasting six months or more. Additionally, early research on using donor-derived natural killer cells suggests they are safe and may help treat cancer. Combining mogamulizumab with these natural killer cells might enhance the body's ability to fight T-cell lymphoma and leukemia by boosting the immune response against cancer. ^{1 4 5 6 7}

Who Is on the Research Team?

John C Reneau, MD, PhD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 with relapsed or refractory cutaneous T-cell lymphoma or adult T-cell leukemia/lymphoma, who've had at least one prior systemic therapy. Participants must have adequate organ function and performance status, not be pregnant, and free from severe allergies to monoclonal antibodies or certain infections. Those with a history of other cancers may join if they've been disease-free for two years.

Inclusion Criteria

Absolute neutrophil count >= 1000/mm^3

I can understand and willingly sign a consent form.

Able to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria

Any illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety

My lymphoma has spread to my brain or spinal cord.

I am experiencing moderate to severe symptoms from a transplant reaction.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive mogamulizumab IV, fludarabine IV, and cyclophosphamide IV, followed by NK cell infusion every 2 weeks for six infusions total

12 weeks

Multiple visits for infusions

Follow-up

Participants are monitored for safety and effectiveness after treatment

28-35 days

Follow-up visits every 3 months for 2 years

Long-term follow-up

Participants are monitored for progression free survival and overall survival

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Mogamulizumab
• Third-Party Natural Killer Cells

Trial Overview The trial is testing the combination of third-party natural killer cells and mogamulizumab to determine the best dose and assess potential benefits/side effects in treating specific lymphomas that are resistant to standard treatments. It's an early-phase study exploring how this immunotherapy can help control cancer growth.

How Is the Trial Designed?

Group I: Treatment (mogamulizumab, chemotherapy, NK cells) Experimental Treatment 6 Interventions

Patients receive mogamulizumab IV over 60 minutes on day -7 and fludarabine IV and cyclophosphamide IV on days -5 to -3. Patients receive NK cell infusion on day 0. Patients then receive mogamulizumab IV over 60 minutes on days 0, 7, 14, and 28, then every 2 weeks thereafter in the absence of disease progression or unacceptable toxicity.

Mogamulizumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Poteligeo for:

• Mycosis fungoides
• Sézary syndrome

Approved in United States as Poteligeo for:

• Mycosis fungoides
• Sézary syndrome

Approved in Canada as Poteligeo for:

• Mycosis fungoides
• Sézary syndrome

Approved in Japan as Poteligeo for:

• Adult T-cell leukemia-lymphoma
• Cutaneous T-cell lymphoma

Who Is Running the Clinical Trial?

John Reneau

Lead Sponsor

Trials

4

Recruited

90+

Published Research Related to This Trial

A study of 441 patients with aggressive B-cell lymphomas revealed that a homozygous deletion of the NKG2C gene is linked to a three-fold increase in prevalence among patients compared to healthy controls, and is associated with poorer outcomes, including significantly reduced progression-free survival (PFS).

The presence of the HLA-E*01:01 allele was found to be more common in B-NHL patients and correlated with higher rates of complete remission, suggesting that genotyping for NKG2C and HLA-E could help identify risk levels and predict responses to immunotherapy in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic Variants of the NKG2C/HLA-E Receptor-Ligand Axis Are Determinants of Progression-Free Survival and Therapy Outcome in Aggressive B-Cell Lymphoma. Wagner, B., Dührsen, U., Hüttmann, A., et al.[2020]

Chimeric antigen receptor (CAR) T cells have shown great success in treating B-lymphoid cancers, but their production is costly and they can cause significant toxicity, limiting their use to specialized centers.

Natural killer (NK) cells present a promising alternative for cancer treatment due to their strong antitumor activity, safety in allogeneic settings, and potential for off-the-shelf availability, making them a viable option for broader cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive cell therapy using engineered natural killer cells. Rezvani, K.[2022]

Mogamulizumab, an anti-CCR4 receptor antibody, shows promising antitumor activity in treating aggressive T-cell neoplasms like adult T-cell leukemia/lymphoma (ATL) at lower doses compared to other monoclonal antibodies.

Clinical trials indicate that mogamulizumab is effective and well tolerated in patients with relapsed/refractory ATL, leading to its recent regulatory approval in Japan and ongoing evaluations in the U.S. and Europe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mogamulizumab for the treatment of adult T-cell leukemia/lymphoma. de Lartigue, J.[2017]

Natural killer (NK) cells are being explored as a promising strategy to enhance anti-cancer therapies, particularly in their ability to target and kill tumor cells while also producing important immune signals like interferon gamma.

Despite advances in NK cell therapy, challenges remain in treating NK leukemias and lymphomas, which are rare but difficult to manage due to the lack of effective treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in anti-tumor efficacy and malignant transformation of human natural killer cells. VanDeusen, JB., Caligiuri, MA.[2019]

In a study involving 30 patients with advanced leukemia, the use of CTLA4Ig before donor lymphocyte infusion (DLI) led to a significant increase in mature NK cells, which are important for fighting leukemia, while also reducing the risk of acute graft-versus-host disease (GVHD) and nonrelapse mortality (NRM).

The overall survival rate at 18 months was 79%, indicating that CTLA4Ig primed DLI not only enhances NK cell activity but also supports better outcomes in leukemia treatment with fewer side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CTLA4Ig Primed Donor Lymphocyte Infusion: A Novel Approach to Immunotherapy after Haploidentical Transplantation for Advanced Leukemia. Jaiswal, SR., Bhakuni, P., Joy, A., et al.[2020]

The phase I study involving 12 subjects with acute myeloid leukemia or relapsed/refractory multiple myeloma demonstrated that NKG2D-CAR T cells were safe, with no dose-limiting toxicities or significant adverse events observed, indicating a favorable safety profile for this treatment approach.

While no objective tumor responses were achieved, there were transient improvements in hematologic parameters in one AML patient, suggesting potential for disease stability, but further modifications to enhance CAR T-cell expansion and effectiveness may be necessary for better clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of Autologous CAR T Cells Targeting NKG2D Ligands in Patients with AML/MDS and Multiple Myeloma. Baumeister, SH., Murad, J., Werner, L., et al.[2021]

Mogamulizumab, a monoclonal antibody targeting CC chemokine receptor 4, demonstrated significant efficacy in a patient with refractory peripheral T-cell lymphoma (PTCL) who had relapsed after autologous stem cell transplantation.

The treatment with mogamulizumab was well-tolerated, showing no severe adverse events, highlighting its potential as a novel therapeutic option for difficult-to-treat PTCL cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mogamulizumab treatment of refractory peripheral T-cell lymphoma following autologous stem cell transplantation: A case report. Fujita, Y., Nakaya, A., Fujita, S., et al.[2020]

Mogamulizumab is an FDA-approved monoclonal antibody that targets the CCR4 receptor, showing significant improvement in progression-free survival for patients with relapsed or refractory mycosis fungoides or Sézary syndrome compared to vorinostat.

While mogamulizumab offers a new treatment option for T-cell lymphomas, it is associated with serious adverse events such as infusion reactions and increased risk of graft-versus-host disease in certain settings, highlighting the need for careful patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mogamulizumab: An Anti-CC Chemokine Receptor 4 Antibody for T-Cell Lymphomas. Moore, DC., Elmes, JB., Shibu, PA., et al.[2020]

In a study of 13 patients with cutaneous T-cell lymphoma (CTCL), mogamulizumab treatment led to significant reductions in T cells, with a 57% decrease in total CD3+ T cells and up to 75% in aberrant T cell populations after four treatment cycles.

The reduction in aberrant T cells was noticeable after just one dose of mogamulizumab, indicating its potential effectiveness, although no clear correlation was found between the decrease in aberrant T cells and treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of mogamulizumab on the aberrant T cell population in the peripheral blood - A monocentric retrospective analysis. Gosmann, J., Bielefeld, A., Schmitz, FJ., et al.[2023]

Recent clinical trials have shown that the combination of VCAP-AMP-VECP and mogamulizumab significantly improves complete response rates in aggressive adult T-cell leukemia (ATL), with a higher response rate of 52% compared to 33% for VCAP-AMP-VECP alone.

Mogamulizumab has demonstrated promising efficacy for relapsed ATL and peripheral T-cell lymphomas (PTCLs), indicating its potential as a new treatment option for these challenging malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disease-oriented treatment of T/NK-cell lymphomas. Tobinai, K.[2017]

Pretransplantation use of mogamulizumab (Mog) in patients with aggressive adult T-cell leukemia/lymphoma (ATLL) significantly increased the risk of severe acute graft-versus-host disease (GVHD) and refractoriness to treatment, indicating potential safety concerns.

Patients who received Mog before allogeneic hematopoietic stem-cell transplantation (allo-HSCT) had a higher one-year nonrelapse mortality rate (43.7% vs. 25.1%) and lower overall survival (32.3% vs. 49.4%) compared to those who did not, suggesting that Mog may negatively impact clinical outcomes in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pretransplantation Anti-CCR4 Antibody Mogamulizumab Against Adult T-Cell Leukemia/Lymphoma Is Associated With Significantly Increased Risks of Severe and Corticosteroid-Refractory Graft-Versus-Host Disease, Nonrelapse Mortality, and Overall Mortality. Fuji, S., Inoue, Y., Utsunomiya, A., et al.[2021]

CAR-T cell therapy has shown success in treating blood cancers but is limited by risks like graft-versus-host disease and lengthy production times.

CAR-NK cell therapies offer a promising alternative as they can be produced as off-the-shelf products, potentially providing a safer and more efficient treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-NK for tumor immunotherapy: Clinical transformation and future prospects. Wang, W., Jiang, J., Wu, C.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8157723/

Safety and efficacy profile of mogamulizumab (Poteligeo) in ... Based on present evidence, we believed that mogamulizumab had clinically meaningful antitumor activity with acceptable toxicity which is a novel therapy in ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e18603

Efficacy and manageable toxicity of mogamulizumab in a ... Mogamulizumab, a CCR4-targeting monoclonal antibody, is FDA-approved for relapsed cutaneous T-cell lymphoma and has shown efficacy in Japanese ...

3. kkna.kyowakirin.com kkna.kyowakirin.com/media-center/new-data-from-mavoric-trial-sheds-light-on-key-characteristics-of-long-term-poteligeo-mogamulizumab-kpkc-responders-with-specific-subtypes-of-cutaneous-t-cell-lymphoma/

New Data from MAVORIC Trial Sheds Light on Key ... Responses in blood and skin lasting ≥6 months were seen in 49.2% and 27.4% of mogamulizumab-treated patients, respectively, compared with 5.6% and 7.5% with ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/hon.3292

Safety and effectiveness of mogamulizumab in relapsed or ... The ORR among subtypes matched that of previous trials (50.0% for angioimmunoblastic T-cell lymphoma; 18.8% for PTCL-not otherwise specified in ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06698003

A Study of Mogamulizumab to Prevent Adult T-cell ... The purpose of this study is to find out whether the study drug mogamulizumab is effective in preventing the development of adult T-cell leukemia/lymphoma ...

6. kyowakirin.com kyowakirin.com/media_center/news_releases/2020/pdf/e20200131_01.pdf

Kyowa Kirin Announces Final Safety Data of POTELIGEO® ... MAVORIC is the first pivotal trial in cutaneous T-cell lymphoma (CTCL) to use progression free survival (PFS) as a primary endpoint.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6850465/

Safety and effectiveness of mogamulizumab in relapsed or ... In the safety analysis population, the mean number of mogamulizumab administrations was 5.4, and 60% of patients did not complete all eight courses of ...