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

Active, not recruiting
Conditions
Primary Hemophagocytic Lymphohistiocytosis
Macrophage 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
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
Evaluate infectious complications and their risk factors in patients who receive CAR-T cell therapy for cancer2 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 resolution2 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 survival2 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 toxicities2 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 infusions2 years

Summary of factors associated with response to second CAR T-cell infusion

Evaluate impact of race/ethnicity and obesity on CAR T-cell outcomes2 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 infusion2 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 therapy2 years

Summary of outcomes of patients with ALL and Down Syndrome who have received CAR T-cell therapy

Evaluate absolute lymphocyte count following lymphodepleting chemotherapy2 years

Summary of absolute lymphocyte count across lymphodepleting regimens

Evaluate relationship between clinical variable and apheresis and manufacturing products2 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 complications2 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 program2 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 efficacy2 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/hematogones2 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 management2 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 outcomes2 Years

Summary of the role of manufacturing changes on CAR T-cell outcomes

Evaluate CAR T-cell related coagulopathies2 Years

Summary of CAR T-cell related coagulopathies

Evaluate long-term outcomes of survivors who received CAR T-cell therapy2 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 infusion2 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 disease2 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 MRD2 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 outcomes2 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

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