Retrospective Study of Immunotherapy Related Toxicities and Factors Impacting Outcomes in Children and Adults With Cancer
- Conditions
- Primary Hemophagocytic LymphohistiocytosisMacrophage Activation Syndrome
- Registration Number
- NCT03827343
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
Immunotherapy is changing the landscape of cancer therapy. Particularly unique to immunotherapy is the toxicity profile, which differs from chemotherapy-based strategies and can be associated with inflammatory responses and/or autoimmune type reactions resulting from activation of the immune system. Referred to as immune related adverse events (irAEs), these adverse events may require systemic immunosuppression or have other consequences and present unique management challenges. Specific to CAR T-cell and other adoptive cell therapies is the constellation of symptoms referred to as cytokine release syndrome (CRS), which can range in severity from mild to severe, and can require both cytokine directed blockade and/or systemic immunosuppression to ameliorate the side effects. While side effects may be unique to each individual immunotherapy, and may also be patient specific, cumulative experience will help to inform toxicity profiles and improve management of side effects and overall outcomes.
Given the number of immunotherapeutic approaches at the NCI, the primary goal of this protocol is to facilitate retrospective chart review of various immunotherapy trials at the NCI used in the treatment of cancer to comprehensively study toxicity profiles. This study will not involve the use of specimens or participant contact. All data that is needed has already been collected on the individual treatment protocols and is available in CRIS records or protocol specific databases.
Data will only be collected from treatment protocols where the PI has given permission for use of the data on the trial the subject was enrolled on. This protocol will be amended to incorporate new research objectives and new protocols as necessary....
- Detailed Description
Immunotherapy is changing the landscape of cancer therapy. Particularly unique to immunotherapy is the toxicity profile, which differs from chemotherapy-based strategies and can be associated with inflammatory responses and/or autoimmune type reactions resulting from activation of the immune system. Referred to as immune related adverse events (irAEs), these adverse events may require systemic immunosuppression or have other consequences and present unique management challenges. Specific to CAR T-cell and other adoptive cell therapies is the constellation of symptoms referred to as cytokine release syndrome (CRS), which can range in severity from mild to severe, and can require both cytokine directed blockade and/or systemic immunosuppression to ameliorate the side effects. While side effects may be unique to each individual immunotherapy, and may also be patient specific, cumulative experience will help to inform toxicity profiles and improve management of side effects and overall outcomes.
Given the number of immunotherapeutic approaches at the NCI, the primary goal of this protocol is to facilitate retrospective chart review of various immunotherapy trials at the NCI used in the treatment of cancer to comprehensively study toxicity profiles. This study will not involve the use of specimens or participant contact. All data that is needed has already been collected on the individual treatment protocols and is available in CRIS records or protocol specific databases. Data will only be collected from treatment protocols where the PI has given permission for use of the data on the trial the subject was enrolled on or from standard of care protocols. This protocol will be amended to incorporate new research objectives and new protocols as necessary.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 500
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To develop a retrospective study to allow for comparison of immunotherapy related toxicity profiles and risk factors across a set of protocols in the NCI. 2 years Summary of immunotherapy related toxicity profiles and risk factors across a set of protocols in the NCI.
- Secondary Outcome Measures
Name Time Method Evaluate infectious complications and their risk factors in patients who receive CAR-T cell therapy for cancer 2 years Summary of infectious complications and their risk factors in patients who receive CAR-T cell therapy for cancer
Evaluate the incidence, risk factors for, and treatment of HLH/MAS (now renamed IEC-HS) in patients who receive CAR-T cell therapy. 2 years Incidence and treatment of HLH/MAS (now renamed IEC-HS) in patients who receive CAR-T cell therapy
Incidence and time to resolution 2 years Incidence of and time to resolution of grade 3 and 4 cytopenias post-CAR T-cell therapy in those who achieve a complete remission.
Overall and relapse free survival 2 years Summary of overall and relapse free survival and transplant associated toxicities for patients undergoing HSCT following CAR-T cell therapy
Incidence of end organ toxicities 2 years Incidence of grade 3 and 4 end organ toxicities experienced within the first 30 days of CAR T-cell therapy and includes associations between pre-CAR organ function as well as post-CAR response to such toxicities as well as validate the CAR-Comorbidity Index as predictive model of CRS severity
Evaluate response and toxicity profile of second CAR T-cell infusions 2 years Summary of factors associated with response to second CAR T-cell infusion
Evaluate impact of race/ethnicity and obesity on CAR T-cell outcomes 2 years Summary of response and toxicity profiles in patients based on race/ethnicity and also in those who are obese compared to those who are not.
Evaluate impact of cryopreservation on outcomes following CAR T-cell infusion 2 years Summary of cryopreservation and patients' outcomes following CAR T-cell infusion
Evaluate outcomes for patients with ALL and Down Syndrome following CAR T-cell therapy 2 years Summary of outcomes of patients with ALL and Down Syndrome who have received CAR T-cell therapy
Evaluate absolute lymphocyte count following lymphodepleting chemotherapy 2 years Summary of absolute lymphocyte count across lymphodepleting regimens
Evaluate relationship between clinical variable and apheresis and manufacturing products 2 years Summary of clinical variables and apheresis and manufacturing products
Evaluate incidence of hypertension, identify risk factors for development of hypertension, summarize medical management in CAR setting, and identify complications 2 years Summary of incidence of hypertension, risk factors, medical management and complications
Describe baseline demographics, prior treatment characteristics and outcomes based on patients who are referred to CAR T-cell program 2 years Summary of demographics, prior treatment and outcomes for patients referred to CAR T-cell program
Incidence of pre-infusion BCA and use of BCA as a prognostic marker for CAR T-cell associated toxicity and efficacy 2 years Incidence of BCA pre-infusion and use as a prognostic marker for CAR T-cell associated toxicity and efficacy
Presence and durability of CD72 expression in both B-ALL and normal B-ALL/hematogones 2 years Summary of CD72 expression in both B-ALL and normal B-ALL/hematogones and evaluate use as prognostic marker for CAR T-cell associated toxicity and efficacy
Evaluate interventions, documentation of care goals, and use of palliative care consultation or other symptom management 2 years Summary of interventions, documentation of care goals, and use of palliative care consultation or other symptom management for patients treated with CAR T-cell therapy
Evaluate the role of manufacturing changes on CAR T-cell outcomes 2 Years Summary of the role of manufacturing changes on CAR T-cell outcomes
Evaluate CAR T-cell related coagulopathies 2 Years Summary of CAR T-cell related coagulopathies
Evaluate long-term outcomes of survivors who received CAR T-cell therapy 2 years Summary of long-term outcomes of survivors who received CAR T-cell therapy
Evaluate the use of anti-cytokine therapy to treat toxicities after CAR T-cell infusion 2 Years Summary of the use of anti-cytokine therapy to treat toxicities after CAR T-cell infusion
Evaluate outcomes of CAR T-cells in patients with extramedullary disease 2 Years Summary of outcomes of CAR T-cells in patients with extramedullary disease
Evaluate cross compare responses and outcomes based on NGS MRD and FC MRD 2 Years Summary of cross compare responses and outcomes based on NGS MRD and FC MRD
Evaluate the impact of clonal hematopoiesis on CAR T-cell outcomes 2 Years Summary of the impact of clonal hematopoiesis on CAR T-cell outcomes
Trial Locations
- Locations (1)
National Cancer Institute (NCI)
🇺🇸Bethesda, Maryland, United States