Emapalumab for Non-Hodgkin's Lymphoma

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Matthew Frigault, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

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

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}

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

Trial 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 (Monoclonal Antibodies)

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Massachusetts General Hospital Boston, MA

Dana-Farber Cancer Institute Boston, MA

Who Is Running the Clinical Trial?

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

Swedish Orphan Biovitrum Industry Sponsor

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] Lenalidomide, thalidomide, and pomalidomide (LTP) are immunomodulatory agents approved for use in multiple myeloma, but in some settings, especially with alkylating agents, an increase in Hodgkin lymphoma and other secondary primary malignancies (SPM) has been noted. Some of these malignancies have been linked to Epstein-Barr virus (EBV), raising the possibility that immunomodulatory drugs disrupt latent EBV infection.

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] On the path to successful immunotherapy of hematopoietic tumors, gammadelta T cells offer great promise because of their human leukocyte antigen (HLA)-unrestricted targeting of a wide variety of leukemias/lymphomas. However, the molecular mechanisms underlying lymphoma recognition by gammadelta T cells remain unclear. Here we show that the expression levels of UL16-binding protein 1 (ULBP1) determine lymphoma susceptibility to gammadelta T cell-mediated cytolysis. Consistent with this, blockade of NKG2D, the receptor for ULBP1 expressed on all Vgamma9(+) T cells, significantly inhibits lymphoma cell killing. Specific loss-of-function studies demonstrate that the role of ULBP1 is nonredundant, highlighting a thus far unique physiologic relevance for tumor recognition by gammadelta T cells. Importantly, we observed a very wide spectrum of ULBP1 expression levels in primary biopsies obtained from lymphoma and leukemia patients. We suggest this will impact on the responsiveness to gammadelta T cell-based immunotherapy, and therefore propose ULBP1 to be used as a leukemia/lymphoma biomarker in upcoming clinical trials.

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

Synthetic phosphoantigens enhance human Vgamma9Vdelta2 T lymphocytes killing of non-Hodgkin's B lymphoma. [2021] Non-Hodgkin's B lymphomas (NHL) are often resistant to conventional treatments and, until now, immunotherapeutic approaches against NHL only aimed at inducing anti-tumor effectors. Nevertheless, human blood Vgamma9Vdelta2 T lymphocytes represent an abundant pool of cytotoxic tumor-reactive cells. Vgamma9Vdelta2 T cells are strongly activated by natural compounds, from which powerful synthetic ligands have been derived. These synthetic antigens induce efficient Vgamma9Vdelta2 T cell responses in vitro.

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] To seek for the effective therapeutical method in treating non-Hodgkin's lymphoma (NHL).

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

Antitumor activity and some immunological properties of gammadelta T-cells from patients with gastrointestinal carcinomas. [2017] Human gammadelta T-cells expressing Vgamma2Jgamma1.2Vdelta2-TCR recognize microbial pyrophosphomonoesters in an MHC-independent manner and exert cytotoxic activity on a wide variety of tumor cells. In the present study, the immunological properties of gammadelta T-cells derived from patients with gastrointestinal carcinomas were examined and compared with those from healthy adult individuals, aiming to develop a novel cancer immunotherapy using gammadelta T-cells stimulated with one of the nonpeptide antigens, 2-methyl-3-butenyl-1-pyrophosphate (2M3B1PP).