RECRUITING

Emapalumab Prevention of CAR-T Cell Associated Toxicities

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

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

A Phase 2 Trial of Emapalumab for the Prevention of CAR-T Cell Associated Toxicities

Quick Facts

Study Start:2024-09-18

Study Completion:2027-08-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06550141

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	* 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.

Inclusion Criteria

Exclusion 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.

* 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.

Contacts and Locations

Study Contact

Matthew Frigault, MD

CONTACT

(617) 643-6175

MFRIGAULT@partners.org

Principal Investigator

Matthew Frigault, MD

PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Study Locations (Sites)

Massachusetts General Hospital

Boston, Massachusetts, 02114

United States

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

United States

Collaborators and Investigators

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

Matthew Frigault, MD, PRINCIPAL_INVESTIGATOR, Massachusetts General Hospital

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-09-18

Study Completion Date2027-08-01

Study Record Updates

Study Start Date2024-09-18

Study Completion Date2027-08-01

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

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