Emapalumab Prevention of CAR-T Cell Associated Toxicities

NCT ID: NCT06550141

Last Updated: 2025-11-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

28 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-09-18

Study Completion Date

2027-08-01

Brief Summary

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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

Detailed Description

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This is a phase 2 multi-center, open label study that is evaluating the safety and efficacy of emapalumab in preventing toxicities associated with axicabtagene ciloleucel in subjects with second- or third-line large B-cell non-Hodgkin's lymphoma.

A phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.

The U.S. Food and Drug Administration (FDA) has not approved emapalumab for the participants specific disease, but it has been approved for other uses.

The U.S. FDA has approved axicabtagene ciloleucel for the participants specific disease.

This research study procedures include screening for eligibility, study treatment including collection of T cells (leukapheresis), lymphodepleting chemotherapy, treatment with emapalumab and axicabtagene ciloleucel, and follow-up evaluations.

Once study treatment is completed, the participants will be followed for up to 24 months.

It is expected that about 28 people will take part in this research study.

Conditions

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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

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Emapalumab

Intervention Type DRUG

An interferon gamma (IFNγ) blocking antibody

Cyclophosphamide

Intervention Type DRUG

Alkylating agent

Fludarabine Phosphate

Intervention Type DRUG

Purine antagonist antimetabolite

Axicabtagene Ciloleucel

Intervention Type DRUG

Autologous treatment

Interventions

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Emapalumab

An interferon gamma (IFNγ) blocking antibody

Intervention Type DRUG

Cyclophosphamide

Alkylating agent

Intervention Type DRUG

Fludarabine Phosphate

Purine antagonist antimetabolite

Intervention Type DRUG

Axicabtagene Ciloleucel

Autologous treatment

Intervention Type DRUG

Other Intervention Names

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Human anti-interferon gamma (IFNγ) monoclonal antibody Gamifant

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Swedish Orphan Biovitrum

INDUSTRY

Sponsor Role collaborator

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

OTHER

Sponsor Role lead

Responsible Party

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

Sponsor-Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Matthew Frigault, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

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Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status NOT_YET_RECRUITING

Countries

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United States

Central Contacts

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Matthew Frigault, MD

Role: CONTACT

Phone: (617) 643-6175

Email: [email protected]

Facility Contacts

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Matthew Frigault, MD

Role: primary

Caron Jacobson, MD

Role: primary

Other Identifiers

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24-317

Identifier Type: -

Identifier Source: org_study_id