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

NCT03827343 | Active Not Recruiting

• 2 other identifiers: 99991904419-C-N044
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

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.

Conditions

Primary Hemophagocytic Lymphohistiocytosis; Macrophage Activation Syndrome

Keywords

CAR-T Cell Therapy; Macrophage Activation Syndrome (MAS); Hemophagocytic Lymphohistiocytosis (HLH); Natural History

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (24)

• Evaluate 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 (now renamed IEC-HS) in patients who receive CAR-T cell therapy.

  2 years

• Incidence and time to resolution

  2 years

• Overall and relapse free survival

  2 years

• Incidence of end organ toxicities

  2 years

Study Arms (1)

1

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

Eligibility Criteria

• Age: 1 Month - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

* 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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Cancer Institute (NCI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 40953923 DERIVED

• 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.

  PMID: 37486616 DERIVED

• 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.

  PMID: 37394115 DERIVED

MeSH Terms

Conditions

Macrophage Activation Syndrome; Lymphohistiocytosis, Hemophagocytic

Condition Hierarchy (Ancestors)

Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Nirali N Shah, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2019
• First Posted: February 1, 2019
• Study Start: January 23, 2019
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-04-29

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.

Locations

US (1)