Emapalumab for Non-Hodgkin's Lymphoma

Recruiting at 1 trial location

Overseen By Matthew Frigault, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Marcela V. Maus, M.D.,Ph.D.

Must not be taking: JAK inhibitors, TNF inhibitors

Disqualifiers: Richter's transformation, Active infection, Hepatitis B/C, 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 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 2 days

28 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that at least 2 weeks or 5 half-lives, whichever is shorter, must have passed since any prior systemic therapy before starting the study, except for certain immune therapies which have different requirements. Steroids require a 7-day washout period (time without taking the medication).

What makes the drug Emapalumab unique for treating non-Hodgkin's lymphoma?

Emapalumab is unique because it targets and neutralizes interferon gamma, a protein involved in inflammation, which is different from traditional chemotherapy or immunotherapy approaches that directly target cancer cells. This mechanism may offer a novel way to manage non-Hodgkin's lymphoma, especially in cases where other treatments are not effective. ^{1 2 3 4 5}

What is the purpose of this trial?

This research study involves assessing the impact of emapalumab as preventative management of CAR-T related cytokine release syndrome in participants with Non-Hodgkin's lymphoma (NHL). The research study involves the following study interventions: * Fludarabine and cyclophosphamide (Lymphodepleting Chemotherapy) * Axicabtagene Ciloleucel * Emapalumab

Research Team

Matthew Frigault, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for individuals with various types of Non-Hodgkin's Lymphoma, including Large B-Cell and Follicular Lymphoma. Participants should not have had previous CAR-T therapy or stem cell transplant within a certain time frame, must meet specific blood count criteria, and cannot be pregnant or breastfeeding.

Inclusion Criteria

My large B-cell lymphoma didn't respond to my first chemoimmunotherapy or came back within a year.

At least 1 measurable lesion per Lugano at time of screening

It has been long enough since my last immune therapy to start a new treatment.

Exclusion Criteria

I have a history of hepatitis B or C.

I need specific medications for my autoimmune disease when starting treatment.

Participants who are receiving any other investigational agents for this condition

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Lymphodepleting Chemotherapy

Participants receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine once a day for 3 days

3 days

3 visits (in-person)

Treatment

Participants receive emapalumab and axicabtagene ciloleucel. Emapalumab is given as a single dose on Day -1, and axicabtagene ciloleucel is given once on Day 0

2 days

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment for cytokine release syndrome and other outcomes

24 months

Regular visits (in-person and virtual)

Treatment Details

Interventions

• Emapalumab

Trial Overview The study tests if emapalumab can prevent side effects from CAR-T cell therapy in lymphoma patients. It includes lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by axicabtagene ciloleucel (CAR-T) treatment, then emapalumab administration.

Participant Groups

Group I: Emapalumab Experimental Treatment 4 Interventions

Leukapheresis will happen within approximately 5 days of eligibility confirmation. Emapalumab is given as a single dose on Day -1 by intravenous infusion over about 1 hour. Lymphodepleting Chemotherapy with cyclophosphamide and fludarabine will occur once a day for 3 days (Days -5 through Day -3) by intravenous infusion over about 2-4 hours. Axicabtagene ciloleucel will be given once on Day 0 by intravenous infusion over about 30 minutes.

Emapalumab is already approved in United States for the following indications:

Approved in United States as Gamifant for:

• Primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy

Who Is Running the Clinical Trial?

Marcela V. Maus, M.D.,Ph.D.

Lead Sponsor

Trials

6

Recruited

110+

Swedish Orphan Biovitrum

Industry Sponsor

Trials

103

Recruited

13,300+

Dr. Guido Oelkers

Swedish Orphan Biovitrum

Chief Executive Officer since 2017

PhD in Economics

Dr. Lydia Abad-Franch

Swedish Orphan Biovitrum

Chief Medical Officer since 2023

MD, MBA

Findings from Research

Lenalidomide, thalidomide, and pomalidomide (LTP) can reactivate Epstein-Barr virus (EBV) in infected B-cell lines, with pomalidomide being the most potent, which raises concerns about the potential for increased secondary malignancies in patients treated with these drugs.

The combination of lenalidomide with other treatments, such as dexamethasone or melphalan, significantly enhances EBV reactivation, suggesting that these immunomodulatory agents may disrupt latent EBV infection and potentially contribute to immune suppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide, Thalidomide, and Pomalidomide Reactivate the Epstein-Barr Virus Lytic Cycle through Phosphoinositide 3-Kinase Signaling and Ikaros Expression. Jones, RJ., Iempridee, T., Wang, X., et al.[2023]

The study reveals that the expression levels of UL16-binding protein 1 (ULBP1) are crucial for how effectively gammadelta T cells can recognize and kill lymphoma cells, indicating a specific mechanism of action for these immune cells.

Given the variability of ULBP1 expression in patient biopsies, it could serve as a valuable biomarker to predict the effectiveness of gammadelta T cell-based immunotherapy in treating hematopoietic tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The MHC class Ib protein ULBP1 is a nonredundant determinant of leukemia/lymphoma susceptibility to gammadelta T-cell cytotoxicity. Lança, T., Correia, DV., Moita, CF., et al.[2022]

Vgamma9Vdelta2 T cells can effectively recognize and kill B lymphoma cells, demonstrating their potential as a therapeutic target in treating Non-Hodgkin's lymphomas.

The use of specific synthetic ligands significantly enhances the proliferation and cytotoxic activity of Vgamma9Vdelta2 T cells against B lymphomas, suggesting a promising strategy for improving immunotherapy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthetic phosphoantigens enhance human Vgamma9Vdelta2 T lymphocytes killing of non-Hodgkin's B lymphoma. Sicard, H., Al Saati, T., Delsol, G., et al.[2021]

In a study of 167 non-Hodgkin's lymphoma patients, combining Chinese herbs with chemotherapy resulted in a significantly higher effective rate (91.96%) and improved survival rates compared to chemotherapy alone (72.73%).

The combination therapy not only enhanced immune function, as indicated by increased NK cell activity, but also reduced blood viscosity, with fewer and milder side effects compared to chemotherapy alone, suggesting it is a safe and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical observation on 112 cases with non-Hodgkin's lymphoma treated by Chinese herbs combined with chemotherapy]. Guo, XM., Li, JX., Yang, XF.[2016]

Gammadelta T-cells from patients with gastrointestinal carcinomas showed strong immune responses when stimulated with the nonpeptide antigen 2M3B1PP, comparable to those from healthy individuals, indicating their potential for effective cancer immunotherapy.

These T-cells not only proliferated vigorously but also produced significant amounts of the inflammatory cytokine IFN-gamma and demonstrated potent cytotoxic activity against both allogeneic and autologous tumor cells, suggesting they could be harnessed to target and destroy cancer cells effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity and some immunological properties of gammadelta T-cells from patients with gastrointestinal carcinomas. Murayama, M., Tanaka, Y., Yagi, J., et al.[2017]

References

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

Lenalidomide, Thalidomide, and Pomalidomide Reactivate the Epstein-Barr Virus Lytic Cycle through Phosphoinositide 3-Kinase Signaling and Ikaros Expression. [2023]

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

The MHC class Ib protein ULBP1 is a nonredundant determinant of leukemia/lymphoma susceptibility to gammadelta T-cell cytotoxicity. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Synthetic phosphoantigens enhance human Vgamma9Vdelta2 T lymphocytes killing of non-Hodgkin's B lymphoma. [2021]

4. China pubmed.ncbi.nlm.nih.gov

[Clinical observation on 112 cases with non-Hodgkin's lymphoma treated by Chinese herbs combined with chemotherapy]. [2016]

5. Greece pubmed.ncbi.nlm.nih.gov

Antitumor activity and some immunological properties of gammadelta T-cells from patients with gastrointestinal carcinomas. [2017]