Large B-cell LymphomaPhase 2NCT06550141
Emapalumab Prevention of CAR-T Cell Associated Toxicities
A Phase 2 study testing Emapalumab, Cyclophosphamide and Fludarabine Phosphate in people with Large B-cell Lymphoma and Relapsed Non-Hodgkin Lymphoma, run by Marcela V. Maus, M.D.,Ph.D. at 2 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Large B-cell Lymphoma, Relapsed Non-Hodgkin Lymphoma, Refractory Non-Hodgkin Lymphoma
- What is being tested?
- Emapalumab, Cyclophosphamide and Fludarabine Phosphate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 2 sitesUnited States
- Study dates
- 18 Sep 2024to 1 Aug 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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
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- 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.
Who cannot join
- 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.
- Autologous stem cell transplant within 6 weeks of planned CAR-T 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.
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- 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 CAR-T
- 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.
- 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.
- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Matthew Frigault, MD, 617-643-6175, MFRIGAULT@partners.org
Matthew Frigault, MD
- Not yet recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Caron Jacobson, MD, (617)-632-5847, Caron_Jacobson@DFCI.HARVARD.EDU
About this study
Official title: A Phase 2 Trial of Emapalumab for the Prevention of CAR-T Cell Associated Toxicities
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 or Lisocabtagene Maraleucel
- Emapalumab
Read the 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 FDA Approved, CD19-directed CAR-T 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 and lisocabtagene maraleucel 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 or lisocabtagene maraleucel, 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
- 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
- Being tested
- Emapalumab, Cyclophosphamide, Fludarabine Phosphate, Axicabtagene Ciloleucel, Dexamethasone
- Keywords
- Second Line Large B-cell Non-Hodgkin's Lymphoma, Third Line Large B-cell Non-Hodgkin's Lymphoma
- Medical subject headings
- Lymphoma, Non-Hodgkin, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EmapalumabDrug
Also called Human anti-interferon gamma (IFNγ) monoclonal antibody, Gamifant
An interferon gamma (IFNγ) blocking antibody
CyclophosphamideDrug
Alkylating agent
Purine antagonist antimetabolite
Axicabtagene CiloleucelDrug
Autologous treatment
DexamethasoneDrug
Corticosteroid
Lisocabtagene maraleucelDrug
Autologous treatment
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1a | Experimental | Leukapheresis will happen within approximately 5 days of eligibility confirmation.
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.
Patients will receive emapalumab 3mg/kg on day -1.
FDA Approved CAR-T will be given once on Day 0 by intravenous infusion over about 30 minutes. Receives: Drug: Emapalumab; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Drug: Axicabtagene Ciloleucel |
| Cohort 1b | Experimental | Leukapheresis will happen within approximately 5 days of eligibility confirmation.
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.
FDA Approved CAR-T will be given once on Day 0 by intravenous infusion over about 30 minutes.
Patients will start dexamethasone 10mg PO daily starting on day 0 through day +2.
Patients will receive emapalumab 3mg/kg on day +1. Receives: Drug: Emapalumab; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Drug: Axicabtagene Ciloleucel; Drug: Dexamethasone |
| Cohort 2a | Experimental | Leukapheresis will happen within approximately 5 days of eligibility confirmation.
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.
Patients will receive emapalumab 3mg/kg on day -1.
Lisocabtagene maraleucel will be given once on Day 0 by intravenous infusion over about 30 minutes. Receives: Drug: Emapalumab; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Drug: Lisocabtagene maraleucel |
| Cohort 2b | Experimental | Leukapheresis will happen within approximately 5 days of eligibility confirmation.
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.
Lisocabtagene maraleucel will be given once on Day 0 by intravenous infusion over about 30 minutes.
Patients will start dexamethasone 10mg PO daily starting on day 0 through day +2.
Patients will receive emapalumab 3mg/kg on day +1. Receives: Drug: Emapalumab; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Drug: Dexamethasone; Drug: Lisocabtagene maraleucel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day -1 to 24 months post treatment
Secondary outcomes (2)
Rate and severity of ICANS as per ASTCT
Assessed using American Society for Transplantation and Cellular Therapy (ASTCT). The rate and severity of immune cell associated neurotoxicity syndrome (ICANS) within the first 30 days of infusion.
Measured: 30 days
Objective response rate (ORR)
The incidence of either a complete response or a partial response by Lugano. All subjects that do not meet the criteria for an objective response by the analysis data cutoff date will be considered non-responders.
Measured: Day -1 to 24 months post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2024
- Study start18 Sep 2024
- Primary completion1 Aug 2027 (estimated)
- Study completion1 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Large B-cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Marcela V. Maus, M.D.,Ph.D.
- Sponsor type
- University, hospital or other
- Collaborators
- Swedish Orphan Biovitrum
- Responsible party
- Sponsor-investigator, Marcela V. Maus, M.D.,Ph.D., Massachusetts General Hospital
- Investigators
- Matthew Frigault, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06550141
- Sponsor's protocol ID
- 24-317
- Status last verified
- Oct 2026
- First submitted
- 5 Aug 2024
- Last updated
- 6 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.