Emapalumab Prophylaxis of Bispecific T-Cell Engagers (BiTEs) Associated CRS and ICANS

A Phase II Study of the Interferon Gamma Inhibitor Emapalumab for Prophylaxis of Cytokine Release Syndrome and Immune Effector Cell-Associated Neurotoxicity Syndrome in Patients With Lymphoma and Multiple Myeloma Receiving Bispecific T-Cell Engagers

The purpose of this study is to evaluate emapalumab as a prophylactic therapy in preventing cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in patients with hematologic malignancies receiving bispecific antibodies (BsAbs) as outpatient. The primary objectives of this study are to evaluate the efficacy, safety, and feasibility of prophylaxis with the interferon gamma (IFN-У -γ) inhibitor Emapalumab in preventing CRS and/or ICANS in patients receiving bispecific antibody therapy for hematologic malignancies.

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Myeloma; Large B-cell Lymphoma (LBCL)
• Intervention / Treatment: Drug: Emapalumab

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Oscar B. Lahoud, MD; Phone Number: 646-754-8570; Email: Oscar.lahoud@nyulangone.org
• Study Contact Backup: Name: Gabrielle Gargano, BS, CCRC; Phone Number: 718-753-8948; Email: Gabrielle.Gargano@nyulangone.org

Study Locations

• United States
  • New York
    • Brooklyn, New York, United States, 11220
      • NYU Langone Health Perlmutter Cancer Center - Sunset Park
    • Manhattan, New York, United States, 10016
      • NYU Langone Health Perlmutter Cancer Center - Manhattan
    • Mineola, New York, United States, 11501
      • NYU Langone Health - Long Island

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Disease Criteria:

   1. Adult patients (≥18 years) with large B-cell lymphoma (LBCL) that is refractory to first-line chemoimmunotherapy or that relapsed after first-line chemoimmunotherapy not eligible for high-dose therapy/autologous stem cell transplantation (HDT-ASCT) or Chimeric Antigen Receptor T- cell (CAR-T) therapy, or adult patients with relapsed/refractory (R/R) LBCL after two or more lines of systemic therapy, who are planned to receive a commercially approved bispecific antibody therapy (e.g. epcoritamab, glofitamab). This includes:

      • Diffuse large B-cell lymphoma (DLBCL) not otherwise specified,
      • Primary mediastinal large B-cell lymphoma,
      • High-grade B-cell lymphoma,
      • DLBCL arising from follicular lymphoma.
   2. Adult patients with R/R multiple myeloma (MM) who have received multiple lines of therapy and are planned to receive a commercially approved bispecific antibody therapy. These prior therapies will typically include a proteasome inhibitor (e.g., bortezomib, carfilzomib), an immunomodulatory drug (e.g., lenalidomide, pomalidomide), and an anti-CD38 monoclonal antibody (e.g., daratumumab).

2. Treatment Eligibility:

   1. At least measurable disease per Lugano Criteria (for B-cell lymphomas) or per International Myeloma Working Group (IMWG) criteria (for multiple myeloma) at the time of screening.
   2. 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 bispecific antibody therapy, except for systemic inhibitory/stimulatory immune checkpoint therapy. Steroids require only a 7-day washout.
   3. At least 3 half-lives must have elapsed from any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy (e.g., ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists, etc.) before the planned bispecific therapy.

3. Performance Status:

   1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

4. Organ Function:

   1. Adequate renal, hepatic, pulmonary, and cardiac function, defined as:
   2. Absolute neutrophil count (ANC) ≥ 1000/µL,
   3. Platelet count ≥ 50,000/µL,
   4. Hgb > 7, and standard pre-medications are allowed per standard of care guidelines
   5. Patients eligible to receive the bispecifics per institutional guidelines.
   6. Absolute lymphocyte count ≥ 100/µL
   7. Creatinine clearance (as estimated by Cockcroft Gault or CKD-EPI) ≥ 30 mL/min,
   8. Serum ALT/AST ≤ 2.5 times institutional upper limit of normal (ULN),
   9. Total bilirubin ≤ 1.5 mg/dL, except in subjects with Gilbert's syndrome,
   10. Cardiac ejection fraction ≥ 40%, no clinically significant pericardial effusion, and no clinically significant ECG findings (current status)
   11. Baseline oxygen saturation > 92% on room air.

5. Reproductive Status:

   1. 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.
   2. Women of Childbearing Potential (WOCBP) must agree to use one highly effective method of contraception, including hormonal contraceptives (e.g. combined oral contraceptives, patch, vaginal ring, injectables, and implants); intrauterine device (IUD) or intrauterine system (IUS); vasectomy or tubal ligation; and one effective method of contraception, including male condom, female condom, cervical cap, diaphragm or contraceptive sponge or abstain from heterosexual intercourse for the duration of study participation and for six months after the last bispecific antibody dose..
   3. Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment.

6. 6. Consent:

   1. Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

1. Other Malignancies:

   a. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, breast) unless disease-free for at least 2 years.

   b. History of Richter's transformation of chronic lymphocytic leukemia (CLL).

2. Stem Cell Transplantation:

   1. Autologous stem cell transplant within 6 weeks of planned bispecific antibody therapy.
   2. History of allogeneic stem cell transplantation within 6 months of planned bispecific antibody.

3. Infections:

   1. Presence of uncontrolled fungal, bacterial, viral, or other infections at the time of screening.
   2. Patients with uncontrolled hepatitis B or C infection. Subjects with positive Hepatitis B or C serology should be started on appropriate antiviral therapy prior to Emapalumab infusion.
   3. Patients must be negative for tuberculosis (TB). Subjects positive for latent tuberculosis prior to study must be started on or have completed with appropriate treatment prior to emapalumab infusion.
   4. Patients must be negative for active cytomegalovirus (CMV, NAT), Epstein-Barr virus (EBV, NAT), and adenovirus (NAT) by PCR testing.

4. Central nervous system (CNS) Disorders:

   a. Evidence of active CNS disease, regardless of prior CNS history. b. History or presence of CNS disorder such as seizure disorder or cerebrovascular ischemia/hemorrhage within 6 months of enrollment.

5. Cardiac and Pulmonary Events:

   1. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months of enrollment.
   2. History of symptomatic pulmonary embolism within 3 months of enrollment (ongoing anticoagulation is allowed if beyond 3 months).

6. Autoimmune Disease:

   a. History of autoimmune disease requiring ongoing systemic immunosuppression. Steroids are allowed up to 5mg prednisone-equivalent for adrenal insufficiency.

   b. Patients anticipated to require canakinumab, Janus kinase (JAK) inhibitors, Tumor necrosis factor (TNF) inhibitors, or tocilizumab for baseline autoimmune/inflammatory disease at the time of bispecific antibody therapy initiation.

7. Vaccination:

   1. Receipt of a Bacillus Calmette-Guérin (BCG) vaccine within 12 weeks prior to screening.
   2. Receipt of any live or attenuated live vaccine (other than BCG) within 4 weeks prior to screening.

8. Investigational Agents:

   a. Participants receiving any other investigational agents for their condition.

9. Pregnancy or Breastfeeding:

   a. Females who are pregnant or breastfeeding, or participants unwilling to use birth control during the study and for 6 months after bispecific therapy.

10. Inability to Participate:

    1. In the investigator's judgment, subjects unlikely to complete all protocol required study visits or procedures, including follow-up visits, or comply with study participation requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prophylactic Emapalumab; Participants will receive the investigational IFN-У inhibitor Emapalumab prior to the intended standard bispecific antibody therapy for lymphoma and multiple myeloma.	Drug: Emapalumab; 1.0 mg/kg IV one day prior to bispecific antibody therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with cytokine release syndrome (CRS) (grades 2-5, as per ASTCT criteria) and/or immune effector cell-associated neurotoxicity syndrome (ICANS) (grades 2-5, per ASTCT criteria) within 30 days of bispecific antibody administration.	Within 30 days of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to onset of first occurrence of CRS/ICANS by grades 2-5		Within 30 days of treatment
Number of participants with grade 3 or higher CRS		Within 30 days of treatment
Number of participants with grade 3 or higher ICANS		Within 30 days of treatment
Number of participants with any grade non-hematologic adverse events (AEs)		Within 30 days of treatment
Number of participants with grade hematologic AEs		Within 30 days of treatment
Number of participants hospitalized within 30 days of treatment		Within 30 days of treatment
Mean CRS grade	Cytokine release syndrome (CRS) grades range from 2-5, the higher the grade the more severe the event.	Within 30 days of treatment
Mean ICANS grade	Immune effector cell-associated neurotoxicity syndrome (ICANS) grades range from 2-5, the higher the grade the more severe the event.	Within 30 days of treatment

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Oscar B. Lahoud, MD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Estimated): May 11, 2026
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): May 31, 2029

Study Registration Dates

• First Submitted: April 28, 2026
• First Submitted That Met QC Criteria: April 28, 2026
• First Posted (Actual): May 5, 2026

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Emapalumab
• Other Study ID Numbers: 25-00098

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The de-identified participant data from the final research dataset will be shared upon reasonable request beginning 9 to 36 months after publication or as required by a condition of awards or supporting agreements, provided the requesting investigator executes a data use agreement with NYU Langone Health. This instance of data sharing will also require separate IRB review as well as review from NYU Langone's Data Sharing Strategy Board (DSSB). Requests should be directed to: Oscar.lahoud@nyulangone.org. The protocol and statistical analysis plan will be posted on Clinicaltrials.gov only as required by federal regulation or supporting awards and agreements.
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• IPD Sharing Access Criteria: The investigator who proposed to use the data will be granted access upon reasonable request. Requests should be directed to Oscar.lahoud@nyulangone.org. To gain access, data requestors will need to sign a data access agreement. This instance of data sharing will also require separate IRB review as well as review from NYU Langone's DSSB.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No