Emapalumab Prevention of CAR-T Cell Associated Toxicities

NCT06550141 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 24-317
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

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; High-grade B-cell Lymphoma; Follicular Lymphoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Incidence of grade 2+ CRS per ASTCT

  Assessed using American Society for Transplantation and Cellular Therapy (ASTCT). All participants will be monitored and assessed for grade 2+ cytokine release syndrome (CRS) for 24 months after post treatment.

  Day -1 to 24 months post treatment

Secondary Outcomes (2)

• Rate and severity of ICANS as per ASTCT

  30 days

• Objective response rate (ORR)

  Day -1 to 24 months post treatment

Other Outcomes (3)

• Duration of response (DOR)

  From First Objective Response until date of first documented disease progression or date of death from any cause, assessed up to 24 months post treatment

• Progression-free Survival (PFS)

  From Day 0 until date of first documented disease progression or date of death from any cause, assessed up to 24 months post treatment

• Overall survival (OS)

  From Day 0 until documented date of death from any cause, assessed up to 24 months post treatment

Study Arms (1)

Emapalumab

EXPERIMENTAL

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.

Drug: Emapalumab; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Drug: Axicabtagene Ciloleucel

Interventions

Emapalumab DRUG

An interferon gamma (IFNγ) blocking antibody

Also known as: Human anti-interferon gamma (IFNγ) monoclonal antibody, Gamifant

Emapalumab

Cyclophosphamide DRUG

Alkylating agent

Emapalumab

Fludarabine Phosphate DRUG

Purine antagonist antimetabolite

Emapalumab

Axicabtagene Ciloleucel DRUG

Autologous treatment

Emapalumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Marcela V. Maus, M.D.,Ph.D.: lead
• Swedish Orphan Biovitrum: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular

Interventions

Emapalumab; Antibodies, Monoclonal; Cyclophosphamide; fludarabine phosphate; axicabtagene ciloleucel

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Matthew Frigault, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matthew Frigault, MD

CONTACT

(617) 643-6175; MFRIGAULT@partners.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: August 5, 2024
• First Posted: August 12, 2024
• Study Start: September 18, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: November 14, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (2)