Status:
RECRUITING
Emapalumab Prevention of CAR-T Cell Associated Toxicities
Lead Sponsor:
Marcela V. Maus, M.D.,Ph.D.
Collaborating Sponsors:
Swedish Orphan Biovitrum
Conditions:
Large B-cell Lymphoma
Relapsed Non-Hodgkin Lymphoma
Eligibility:
All Genders
18+ years
Phase:
PHASE2
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 s...
Detailed Description
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 t...
Eligibility Criteria
Inclusion
- 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
- 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.
Key Trial Info
Start Date :
September 18 2024
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
August 1 2027
Estimated Enrollment :
28 Patients enrolled
Trial Details
Trial ID
NCT06550141
Start Date
September 18 2024
End Date
August 1 2027
Last Update
November 14 2025
Active Locations (2)
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1
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
2
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215