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

NCT ID: NCT03827343

Last Updated: 2026-01-14

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 500 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-01-23
• Study Completion Date: 2026-12-31

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.

Conditions

Macrophage Activation Syndrome; Primary Hemophagocytic Lymphohistiocytosis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

1

Retrospective chart review of children and adults with cancer enrolled on immunotherapy treatment protocols in the NCI.

No interventions assigned to this group

Eligibility Criteria

Inclusion 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.

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nirali N Shah, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

National Cancer Institute (NCI)

Bethesda, Maryland, United States

Countries

United States

References

Culbert AA, Gava F, Valtis YK, Satta T, Vora S, Rocco JM, Nussenblatt V, Silbert SK, Shalabi H, Yates B, Park JH, Lamble AJ, Rejeski K, Shah NN. Pre-infusion risk factors predict severe infectious complications of CAR T-cell therapy in pediatric and adult patients with B-ALL. J Immunother Cancer. 2025 Sep 14;13(9):e012436. doi: 10.1136/jitc-2025-012436.

Reference Type: DERIVED

PMID: 40953923 (View on PubMed)

Silbert SK, Madan S, Holland EM, Steinberg SM, Little L, Foley T, Epstein M, Sarkisian A, Lee DW, Nikitina E, Kakumanu S, Ruppin E, Shalabi H, Yates B, Shah NN. A comprehensive analysis of adverse events in the first 30 days of phase 1 pediatric CAR T-cell trials. Blood Adv. 2023 Sep 26;7(18):5566-5578. doi: 10.1182/bloodadvances.2023009789.

Reference Type: DERIVED

PMID: 37486616 (View on PubMed)

Holland EM, Yates B, Steinberg SM, Yuan CM, Wang HW, Annesley C, Shalabi H, Stroncek D, Fry TJ, Krueger J, Jacoby E, Hsieh E, Bhojwani D, Gardner RA, Maude SL, Shah NN. Chimeric Antigen Receptor T Cells as Salvage Therapy for Post-Chimeric Antigen Receptor T Cell Failure. Transplant Cell Ther. 2023 Sep;29(9):574.e1-574.e10. doi: 10.1016/j.jtct.2023.06.019. Epub 2023 Jun 30.

Reference Type: DERIVED

PMID: 37394115 (View on PubMed)

Other Identifiers

19-C-N044

Identifier Type: -

Identifier Source: secondary_id

999919044

Identifier Type: -

Identifier Source: org_study_id