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

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....

Study Overview

• Status: Active, not recruiting
• Conditions: Macrophage Activation Syndrome; Primary Hemophagocytic Lymphohistiocytosis

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.

• Study Type: Observational
• Enrollment (Actual): 500

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Cancer Institute (NCI)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Children and adults with cancer enrolled on immunotherapy treatment protocols in the NCI.

Description

• 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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
1; 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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Nirali N Shah, M.D., National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2019
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: January 31, 2019
• First Submitted That Met QC Criteria: January 31, 2019
• First Posted (Actual): February 1, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 21, 2024

More Information

Terms related to this study

• Keywords: Natural History; CAR-T Cell Therapy; Hemophagocytic Lymphohistiocytosis (HLH); Macrophage Activation Syndrome (MAS)
• Additional Relevant MeSH Terms: Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation Syndrome
• Other Study ID Numbers: 999919044; 19-C-N044

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: .All IPD recorded in the medical record will be shared with intramural investigators upon request.
• IPD Sharing Time Frame: Clinical data available during the study and indefinitely.
• IPD Sharing Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No