Retrospective Study of Immunotherapy Related Toxicities and Factors Impacting Outcomes in Children and Adults With Cancer

Study Overview
=================
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.

Official Title
-----------------
Retrospective Study of Immunotherapy Related Toxicities and Factors Impacting Outcomes in Children and Adults With Cancer

Conditions
-----------------
Macrophage Activation Syndrome, Primary Hemophagocytic Lymphohistiocytosis

Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 1 Month
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>Retrospective chart review of children and adults with cancer enrolled on immunotherapy treatment protocols in the NCI. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Summary of immunotherapy related toxicity profiles and risk factors across a set of protocols in the NCI. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate infectious complications and their risk factors in patients who receive CAR-T cell therapy for cancer | Summary of infectious complications and their risk factors in patients who receive CAR-T cell therapy for cancer | 2 years | 
| Evaluate the incidence, risk factors for, and treatment of HLH/MAS in patients who receive CAR-T cell therapy | Incidence and risk factors for, and treatment of HLH/MAS in patients who receive CAR-T cell therapy | 2 years | 
| Incidence and time to resolution | Incidence of and time to resolution of grade 3 and 4 cytopenias post-CAR T-cell therapy in those who achieve a complete remission. | 2 years | 
| Overall and relapse free survival | Summary of overall and relapse free survival and transplant associated toxicities for patients undergoing HSCT following CAR-T cell therapy | 2 years | 
| Incidence of end organ toxicities | 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 | 2 years | 
| Evaluate response and toxicity profile of second CAR T-cell infusions | Summary of factors associated with response to second CAR T-cell infusion | 2 years | 
| Evaluate impact of race/ethnicity and obesity on CAR T-cell outcomes | 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. | 2 years | 
| Evaluate impact of cryopreservation on outcomes following CAR T-cell infusion | Summary of cryopreservation and patients' outcomes following CAR T-cell infusion | 2 years | 
| Evaluate outcomes for patients with ALL and Down Syndrome following CAR T-cell therapy | Summary of outcomes of patients with ALL and Down Syndrome who have received CAR T-cell therapy | 2 years | 
| Evaluate absolute lymphocyte count following lymphodepleting chemotherapy | Summary of absolute lymphocyte count across lymphodepleting regimens | 2 years | 
| Evaluate relationship between clinical variable and apheresis and manufacturing products | Summary of clinical variables and apheresis and manufacturing products | 2 years | 
| Evaluate incidence of hypertension, identify risk factors for development of hypertension, summarize medical management in CAR setting, and identify complications | Summary of incidence of hypertension, risk factors, medical management and complications | 2 years | 
| Describe baseline demographics, prior treatment characteristics and outcomes based on patients who are referred to CAR T-cell program | Summary of demographics, prior treatment and outcomes for patients referred to CAR T-cell program | 2 years | 
| Incidence of pre-infusion BCA and use of BCA as a prognostic marker for CAR T-cell associated toxicity and efficacy | Incidence of BCA pre-infusion and use as a prognostic marker for CAR T-cell associated toxicity and efficacy | 2 years | 
| Presence and durability of CD72 expression in both B-ALL and normal B-ALL/hematogones | 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 | 2 years | 
| Evaluate interventions, documentation of care goals, and use of palliative care consultation or other symptom management | 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 | 2 years | 
| Evaluate long-term outcomes of survivors who received CAR T-cell therapy | Summary of long-term outcomes of survivors who received CAR T-cell therapy | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CAR-T Cell Therapy, Macrophage Activation Syndrome (MAS), Hemophagocytic Lymphohistiocytosis (HLH), Natural History