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
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).
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.
Single group
Emapalumab
DrugAn interferon gamma (IFNγ) blocking antibody
Cyclophosphamide
DrugAlkylating agent
Fludarabine Phosphate
DrugPurine antagonist antimetabolite
Axicabtagene Ciloleucel
DrugAutologous treatment
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.
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.
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.
Duration of response (DOR)
Among subject who experience an objective response the date of their first objective response to disease progression per Lugano or death regardless of cause. Subjects not meeting the criteria for progression or death by the analysis data cutoff date will be censored at their last evaluable disease assessment date and their response will be noted as ongoing.
Progression-free Survival (PFS)
The time from the axicabtagene ciloleucel infusion date to the date of disease progression per Lugano or death from any cause. Subjects not meeting the criteria for progression by the analysis data cutoff date will be censored at their last evaluable disease assessment date.
Overall survival (OS)
The time from axicabtagene ciloleucel infusion to the date of death. Subjects who have not died by the analysis data cutoff date will be censored at their last contact date.
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Marcela V. Maus, M.D.,Ph.D.
Lead sponsor
Massachusetts General Hospital
Sponsor institution
Swedish Orphan Biovitrum
Collaborator
