Immunotherapy for Lymphoma

Overseen By Yago L Nieto

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Active infection, HIV, Hepatitis B/C, others

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

Compensation: Varies

Number of Visits: 35

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new immunotherapy approach for Hodgkin and non-Hodgkin lymphoma that has not responded to other treatments or has returned. The study tests the effects of combining modified immune cells from umbilical cord blood with an antibody called AFM13 (Acimtamig), which may help the immune system target and destroy cancer cells. The trial aims to determine the best dose and understand any side effects. Individuals with CD30 positive lymphoma that is resistant to treatment or has recurred may be suitable candidates for this trial. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received any anti-cancer treatment within the two weeks before starting the trial.

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

Research has shown that the treatments under study, AFM13 and the combination AFM13-NK, have been safe in earlier studies. Specifically, the AFM13-NK cell treatment was well tolerated, with no reports of serious side effects such as severe immune reactions or nerve problems. Patients did not experience the serious immune reactions sometimes seen with other treatments.

Similarly, AFM13 alone has demonstrated safety. Studies have found it to be generally well tolerated, with manageable side effects. This suggests that both AFM13 and AFM13-NK treatments are likely safe options for patients, based on the data collected so far. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments AFM13 and AFM13-NK because these innovative therapies offer a new approach to tackling lymphoma. Unlike traditional treatments that often rely on chemotherapy and radiation, AFM13 leverages the body's immune system by targeting CD30, a specific protein on lymphoma cells, enhancing the immune response against the cancer. AFM13-NK takes it a step further by combining AFM13 with natural killer cells, which are powerful immune cells that can directly attack cancer cells. This combination aims to boost the effectiveness of immunotherapy, potentially leading to more effective and faster results compared to existing options.

What evidence suggests that this trial's treatments could be effective for lymphoma?

Research has shown that AFM13, a type of antibody, yields promising results in treating certain lymphomas, which are cancers of the lymphatic system. Studies have demonstrated that AFM13 works well for patients whose lymphomas returned after treatment or didn't respond to initial treatments. In this trial, participants will receive AFM13 with NK (natural killer) cells, a combination that has shown even better results. Specifically, previous studies found this combination treatment very effective, with 92.9% of patients showing improvement and 66.7% achieving complete remission. These findings suggest that using AFM13 with NK cells could be a powerful way to treat these difficult cancers. ^{1 2 3 5 6}

Who Is on the Research Team?

Yago L. Nieto

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with recurrent or refractory CD30 positive Hodgkin or non-Hodgkin lymphomas who have adequate organ function and performance status. Women of childbearing potential must not be pregnant, breastfeeding, and agree to use contraception. Exclusions include unresolved severe side effects from prior treatments, active infections requiring IV antibiotics, HIV infection, recent major surgery, other active malignancies (except certain skin cancers), and life expectancy under 6 months.

Inclusion Criteria

Serum creatinine clearance >= 50 ml/min, estimated using the Cockcroft-Gault equation.

Alkaline phosphatase (ALP) =< 2 x ULN.

Bilirubin =< 2 x ULN.

Exclusion Criteria

I am HIV positive.

I have been treated with AFM13 before.

I haven't taken any cancer treatment, including trials, in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Patients receive standard of care fludarabine and cyclophosphamide intravenously

3 days

3 visits (in-person)

Treatment

Patients receive AFM13-NK on day 0 and AFM13 on days 7, 14, and 21

3 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Visits at 28 days, 8 weeks, 100 and 180 days, then every 3-6 months

What Are the Treatments Tested in This Trial?

Interventions

• AFM13
• AFM13-NK

Trial Overview The trial is testing modified NK cells combined with the monoclonal antibody AFM13 (AFM13-NK) followed by AFM13 alone in patients with specific types of lymphoma. The goal is to determine the best dose and observe how well this combination helps the immune system attack cancer cells and potentially reduce tumor growth.

How Is the Trial Designed?

Group I: Treatment (AFM13-NK, AFM13) Experimental Treatment 5 Interventions

Patients receive standard of care fludarabine IV over 1 hour and standard of care cyclophosphamide IV over 30-60 minutes on days -5 to -3, AFM13-NK IV over 4 hours on day 0, and then AFM13 IV over 4 hours on days 7, 14, and 21.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

Natural killer/T cell lymphoma (NKTCL) is a rare and aggressive form of lymphoma associated with Epstein-Barr virus, primarily affecting patients in East Asia and Latin America, and current treatments have limited effectiveness for advanced cases.

Immunotherapy, including strategies targeting PD-1/PD-L1 and CTLA-4, as well as CAR T cell therapy, shows promise in improving outcomes for NKTCL patients, highlighting the need for novel treatment approaches in this challenging disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances and challenges of immunotherapies in NK/T cell lymphomas. He, L., Chen, N., Dai, L., et al.[2023]

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]

Immunotherapy has emerged as a promising treatment for natural killer/T-cell lymphoma (NKTCL), showing good clinical results with targeted antibodies like daratumumab and brentuximab vedotin, especially due to the high expression of programmed death-ligand 1 in NKTCL.

Cellular immunotherapy using engineered cytotoxic T lymphocytes targeting specific viral proteins has demonstrated potential for sustained remission, suggesting it could be effective as maintenance therapy after initial treatment or for relapsed cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updating targets for natural killer/T-cell lymphoma immunotherapy. Xue, W., Zhang, M.[2021]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7008

Results from the completed dose-finding part of phase 2 ... Acimtamig in combination with AlloNK shows promising efficacy with a well-managed safety profile with the potential to address an unmet need in pts with R/R HL.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39531538/

A Phase II Study of Acimtamig (AFM13) in Patients with CD30 ... This study evaluated the efficacy of a novel CD30/CD16A bispecific innate cell engager, acimtamig (AFM13), in patients with R/R PTCL.

3. mdanderson.org mdanderson.org/newsroom/nk-cells-complexed-with-bispecific-antibody-yield-high-response-rates-in-patients-with-lymphoma.h00-159775656.html

NK cells complexed with bispecific antibody yield high ... Phase I trial demonstrates AFM13-NK cells are safe and highly effective in heavily pretreated patients. MD Anderson News Release April 04, ...

4. aacrjournals.org aacrjournals.org/clincancerres/article-pdf/31/1/65/3528390/ccr-24-1913.pdf

A Phase II Study of Acimtamig (AFM13) in Patients with CD30 ... Subgroup analyses revealed pro- nounced efficacy in patients with angioimmunoblastic T-cell lymphoma, a subtype characterized by a highly immune ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11701429/

A Phase II Study of Acimtamig (AFM13) in Patients with CD30 ... This study evaluated the efficacy of a novel CD30/CD16A bispecific innate cell engager, acimtamig (AFM13), in patients with R/R PTCL.

6. affimed.com affimed.com/wp-content/uploads/ASH-2023_4855-Moskowitz_AFM13-LuminICE-203-TIP-Poster_10-Nov.pdf

AFM13 in Combination with Allogeneic Natural Killer Cells ... Cohorts 3 and 4 will only start if no more than one Grade 3 or 4 treatment-related adverse event is observed in the first six patients enrolled.