Recruiting
Phase 2

Emapalumab

Sponsor:

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

Code:

NCT06550141

Conditions

Large B-cell Lymphoma

Relapsed Non-Hodgkin Lymphoma

Refractory Non-Hodgkin Lymphoma

Diffuse Large B Cell Lymphoma

Primary Mediastinal Large B-cell Lymphoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Emapalumab

Cyclophosphamide

Fludarabine Phosphate

Axicabtagene Ciloleucel

Study Details

Brief summary:

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

Conditions

Large B-cell Lymphoma

Relapsed Non-Hodgkin Lymphoma

Refractory Non-Hodgkin Lymphoma

Diffuse Large B Cell Lymphoma

Primary Mediastinal Large B-cell Lymphoma

Study ID

NCT06550141

Start date

Sep 18, 2024

Status verified date

Nov, 2025

Completion date

Aug 1, 2027

Anticipated

Primary completion date

Aug 1, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy. Or adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
  • At least 1 measurable lesion per Lugano at time of screening.
  • At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy however steroids only require a 7-day washout.
  • At least 3 half-lives must have elapsed from any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy at the time the subject is planned for leukapheresis (e.g. ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists, etc).
  • Age 18 or older
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
  • Adequate renal, hepatic, pulmonary and cardiac function defined as:

  • ANC ≥1000/uL
  • Platelet count ≥50,000/uL
  • Absolute lymphocyte count ≥100/uL
  • Creatinine clearance (as estimated by Cockcroft Gault or CKD-EPI) ≥ 30 mL/min
  • Serum ALT/AST ≤2.5 per institutional ULN
  • Total bilirubin ≤1.5 mg/dl, except in subjects with Gilbert's syndrome.
  • Cardiac ejection fraction ≥ 40%, no clinically significant pericardial effusion, and no clinically significant ECG findings
  • Baseline oxygen saturation >92% on room air.
  • Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential).
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) or follicular lymphoma unless disease free for at least 3 years.
  • History of Richter's transformation of CLL.
  • Autologous stem cell transplant within 6 weeks of planned axicabtagene ciloleucel infusion.
  • History of allogeneic stem cell transplantation.
  • Presence of uncontrolled fungal, bacterial, viral, or other infection at time of screening.
  • Known history of acute or chronic active hepatitis B or C infection. Subjects with history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America (IDSA) guidelines.

  • Patients should also be negative for latent Tb, CMV (NAT), EBV (NAT) and adenovirus (NAT) by PCR testing.
  • No evidence of active CNS disease regardless of prior CNS history.
  • History or presence of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage within 6 months of enrollment.
  • History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment.
  • History of symptomatic pulmonary embolism within 3 months of enrollment; ongoing anticoagulation is allowed if beyond 3 months.
  • Any medical condition likely to interfere with assessment of safety or efficacy of study treatment.
  • History of allergic reactions or severe immediate hypersensitivity reaction to any of the agents used in this study or compounds of similar chemical or biologic composition.
  • Females who are pregnant or breastfeeding or female or male participants who are not willing to practice birth control from the time of consent through 6 months after the completion of axicabtagene ciloleucel
  • In the investigators judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.
  • History of autoimmune disease requiring ongoing systemic immunosuppression. Steroids are allowed up to 5mg predinosine-equivalent for adrenal insufficiency.
  • Patients anticipated to require canakinumab, JAK inhibitors, TNF inhibitors, and tocilizumab for non-CAR-T management of baseline autoimmune/inflammatory disease at the time of emapalumab initiation.
  • Receipt of a BCG vaccine within 12 weeks prior to Screening.
  • Receipt of a live or attenuated live (other than BCG) vaccine within 4 weeks prior to screeing.
  • Participants who are receiving any other investigational agents for this condition.

Study Design

Enrollment

28 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Emapalumab

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.

Interventions

Emapalumab

An interferon gamma (IFNγ) blocking antibody

Cyclophosphamide

Alkylating agent

Fludarabine Phosphate

Purine antagonist antimetabolite

Axicabtagene Ciloleucel

Autologous treatment

Primary outcome measure

  • Incidence of grade 2+ CRS per ASTCT [ Time Frame: Day -1 to 24 months post treatment ]

Central Contacts and Locations

Central contacts

Matthew Frigault, MD

(617) 643-6175MFRIGAULT@partners.org

Locations

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Contacts

Matthew Frigault, MD

617-643-6175MFRIGAULT@partners.org

Principal Investigator:

Matthew Frigault, MD

More Information

Sponsor

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

Last update posted

Nov 14, 2025

Last verified

Nov, 2025

Keywords

  • Second Line Large B-cell Non-Hodgkin's Lymphoma
  • Third Line Large B-cell Non-Hodgkin's Lymphoma

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Marcela V. Maus, M.D.,Ph.D. on 2025-11-14.