Clinical trial NCT03827343: Retrospective Study of Immunotherapy Related Toxicities and Factors Impacting Outcomes in Children and Adults With Cancer
Official title: Retrospective Study of Immunotherapy Related Toxicities and Factors Impacting Outcomes in Children and Adults With Cancer
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Macrophage Activation Syndrome
Primary Hemophagocytic Lymphohistiocytosis
Keywords: CAR-T Cell Therapy
Macrophage Activation Syndrome (MAS)
Hemophagocytic Lymphohistiocytosis (HLH)
Natural History
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2019-02-01
Enrollment: 500
Sex: ALL
Minimum age (years): 1
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children and adults with cancer enrolled on immunotherapy treatment protocols in the 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.

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.

Primary outcomes:
measure: 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.
timeFrame: 2 years
Secondary outcomes:
measure: Evaluate infectious complications and their risk factors in patients who receive CAR-T cell therapy for cancer
timeFrame: 2 years
measure: Evaluate the incidence, risk factors for, and treatment of HLH/MAS (now renamed IEC-HS) in patients who receive CAR-T cell therapy.
timeFrame: 2 years
measure: Incidence and time to resolution
timeFrame: 2 years
measure: Overall and relapse free survival
timeFrame: 2 years
measure: Incidence of end organ toxicities
timeFrame: 2 years
measure: Evaluate response and toxicity profile of second CAR T-cell infusions
timeFrame: 2 years
measure: Evaluate impact of race/ethnicity and obesity on CAR T-cell outcomes
timeFrame: 2 years
measure: Evaluate impact of cryopreservation on outcomes following CAR T-cell infusion
timeFrame: 2 years
measure: Evaluate outcomes for patients with ALL and Down Syndrome following CAR T-cell therapy
timeFrame: 2 years
measure: Evaluate absolute lymphocyte count following lymphodepleting chemotherapy
timeFrame: 2 years
measure: Evaluate relationship between clinical variable and apheresis and manufacturing products
timeFrame: 2 years
measure: Evaluate incidence of hypertension, identify risk factors for development of hypertension, summarize medical management in CAR setting, and identify complications
timeFrame: 2 years
measure: Describe baseline demographics, prior treatment characteristics and outcomes based on patients who are referred to CAR T-cell program
timeFrame: 2 years
measure: Incidence of pre-infusion BCA and use of BCA as a prognostic marker for CAR T-cell associated toxicity and efficacy
timeFrame: 2 years
measure: Presence and durability of CD72 expression in both B-ALL and normal B-ALL/hematogones
timeFrame: 2 years
measure: Evaluate interventions, documentation of care goals, and use of palliative care consultation or other symptom management
timeFrame: 2 years
measure: Evaluate long-term outcomes of survivors who received CAR T-cell therapy
timeFrame: 2 years
measure: Evaluate cross compare responses and outcomes based on NGS MRD and FC MRD
timeFrame: 2 Years
measure: Evaluate the role of manufacturing changes on CAR T-cell outcomes
timeFrame: 2 Years
measure: Evaluate the impact of clonal hematopoiesis on CAR T-cell outcomes
timeFrame: 2 Years
measure: Evaluate CAR T-cell related coagulopathies
timeFrame: 2 Years
measure: Evaluate the use of anti-cytokine therapy to treat toxicities after CAR T-cell infusion
timeFrame: 2 Years
measure: Evaluate outcomes of CAR T-cells in patients with extramedullary disease
timeFrame: 2 Years
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Cancer Institute (NCI)
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Nirali N Shah, M.D.
role: PRINCIPAL_INVESTIGATOR
References: