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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called emapalumab (also known as Gamifant) to determine if it can prevent cytokine release syndrome, a condition that can occur after CAR-T therapy. The focus is on individuals with Non-Hodgkin's lymphoma, a type of blood cancer that has not responded well to previous treatments. Participants will also receive other treatments, including chemotherapy and axicabtagene ciloleucel, a type of CAR-T therapy. The trial seeks adults with large B-cell lymphoma that has either returned or not responded to earlier treatments. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

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).

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

Previous studies have shown that emapalumab offers both potential benefits and some risks. For one condition, 53% of patients experienced serious side effects, with infections and stomach bleeding being the most common. However, the FDA has approved emapalumab for other uses, indicating it is considered safe for some patients.

This is a phase 2 study, meaning the treatment has been tested in humans before. The current goal is to learn more about its safety and effectiveness. Phase 2 trials often aim to find the best dose with the fewest side effects.

Prospective participants should know that emapalumab has been used for other conditions, and doctors will closely monitor for any serious side effects. Discuss any concerns with the medical team to understand what this means for participation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Non-Hodgkin's Lymphoma, which often focus on chemotherapy and targeted therapies, Emapalumab is unique because it targets a specific immune pathway. Emapalumab works by inhibiting interferon-gamma, a cytokine involved in inflammation and immune response, which can be overactive in certain cancer conditions. This novel mechanism of action could offer a new therapeutic angle, potentially leading to improved outcomes for patients who may not respond well to current therapies. Researchers are excited about Emapalumab because it represents a shift towards more personalized medicine, aiming to target specific immune dysfunctions in lymphoma.

What evidence suggests that emapalumab might be an effective treatment for Non-Hodgkin's lymphoma?

Research has shown that emapalumab, the investigational treatment in this trial, has been effective in treating similar conditions. For example, in treating macrophage activation syndrome, a related immune disorder, 54% of patients fully recovered, and 82% improved significantly within eight weeks. Emapalumab blocks a protein called interferon gamma, reducing inflammation and the immune response. Although specific data for non-Hodgkin's lymphoma is not available, the drug's ability to manage severe immune reactions suggests it could help prevent cytokine release syndrome (an overreaction of the immune system) in patients receiving CAR-T cell therapy. These findings offer promising support for its potential effectiveness in this trial. ^{1 3 4 5 6}

Who Is on the Research Team?

Matthew Frigault, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

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.

Participants who are receiving any other investigational agents for this condition

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

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1.

sobi.com

sobi.com/en/press-releases/fda-approves-gamifantr-emapalumab-lzsg-first-ever-treatment-adults-and-children-macrophage-activation-syndrome-stills-disease-2342991

FDA approves Gamifant® (emapalumab-lzsg) as first-ever ...

54 percent (21/39) of patients had a complete response at Week 8, and 82% (32/39) achieved clinical MAS remission (VAS ≤1 cm) at Week 8. Safety ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06550141?term=AREA%5BConditionSearch%5D(%22Lymphoma%22)%20AND%20AREA%5BInterventionSearch%5D(%22Antibodies,%20Blocking%22)&rank=1

Emapalumab Prevention of CAR-T Cell Associated Toxicities

This research study involves assessing the impact of emapalumab as preventative management of CAR-T related cytokine release syndrome in participants with ...

3.

gamifant.com

gamifant.com/phlh/results

Primary HLH efficacy data

Gamifant was proven to be effective in a clinical trial · 63% (17/27) overall response rate (ORR) with Gamifant · 70% of patients (19/27) proceeded to HSCT ...

4.

pharmacytimes.com

pharmacytimes.com/view/fda-approves-emapalumab-lzsg-as-first-ever-treatment-for-macrophage-activation-syndrome-in-still-disease

FDA Approves Emapalumab-Lzsg as First-Ever Treatment ...

Clinical trials showed 54% complete response and 82% clinical remission at week 8, confirming emapalumab's efficacy and safety.

5.

gamifantcares.com

gamifantcares.com/studyresults

About Gamifant® (emapalumab-lzsg) | Study results

The safety and effectiveness of Gamifant was studied in a clinical trial for the treatment of primary HLH. The clinical trial looked at: How effective Gamifant ...

6.

gamifant.com

gamifant.com/phlh/safety

Safety Data | Gamifant® (emapalumab-lzsg) For HCPs

Serious adverse reactions were reported in 53% of patients. The most common serious adverse reactions (≥3%) included infections, gastrointestinal hemorrhage ...