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

30 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment AFM13, Acimtamig, AFM13-NK for lymphoma?

Research shows that natural killer (NK) cells, which are part of the immune system, can be used in cancer treatments to help the body fight tumors. NK cell-based therapies have shown promise in early clinical trials for various cancers, suggesting potential effectiveness for lymphoma as well. ^{1 2 3 4 5}

What makes the drug AFM13 unique for treating lymphoma?

AFM13 is unique because it is a first-in-class tetravalent bispecific antibody that targets both CD30 and CD16A, enhancing the ability of natural killer (NK) cells to attack lymphoma cells. This approach differs from traditional treatments by directly engaging the immune system to fight the cancer. ^{6 7 8 9 10}

What is the purpose of this trial?

This phase I/II trial studies the side effects and best dose of modified umbilical cord blood immune cells (natural killer \[NK\] cells) combined with the antibody AFM13 (AFM13-NK) and AFM13 alone in treating patients with CD30 positive Hodgkin lymphoma or non-Hodgkin lymphoma that has come back (recurrent) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as AFM13, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Giving AFM13 loaded with NK cells followed by AFM13 alone may kill more cancer cells and decrease cancer growth in patients with CD30 positive AFM13-NK Hodgkin and Non-Hodgkin lymphomas.

Research Team

Yago L. Nieto

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Natural killer cell-based immunotherapy in cancer: current insights and future prospects. [2021]

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

Natural killer cell neoplasms. [2019]

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

New developments in anti-tumor efficacy and malignant transformation of human natural killer cells. [2019]

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

The natural killer cell immunotherapy platform: An overview of the landscape of clinical trials in liquid and solid tumors. [2023]

5. China pubmed.ncbi.nlm.nih.gov

NK cell-based immunotherapy for malignant diseases. [2022]

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

AFM13: a first-in-class tetravalent bispecific anti-CD30/CD16A antibody for NK cell-mediated immunotherapy. [2018]

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

Advances and challenges of immunotherapies in NK/T cell lymphomas. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Novel Immunotherapy Options for Extranodal NK/T-Cell Lymphoma. [2020]

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

Daratumumab monotherapy for patients with relapsed or refractory natural killer/T-cell lymphoma, nasal type: an open-label, single-arm, multicenter, phase 2 study. [2021]

10. China pubmed.ncbi.nlm.nih.gov

Updating targets for natural killer/T-cell lymphoma immunotherapy. [2021]