Macrophage Activation SyndromeNCT03827343
Retrospective Study of Immunotherapy Related Toxicities and Factors Impacting Outcomes in Children and Adults With Cancer
An observational study of Macrophage Activation Syndrome and Primary Hemophagocytic Lymphohistiocytosis, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 month to 120 years
- Conditions the study is for
- Macrophage Activation Syndrome, Primary Hemophagocytic Lymphohistiocytosis
- How many people
- 500 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Jan 2019to 31 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 120 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Cancer Institute (NCI)
Bethesda, Maryland, 20892
About this study
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.
Read the 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.
- Keywords
- CAR-T Cell Therapy, Macrophage Activation Syndrome (MAS), Hemophagocytic Lymphohistiocytosis (HLH), Natural History
- Medical subject headings
- Macrophage Activation Syndrome, Lymphohistiocytosis, Hemophagocytic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Retrospective chart review of children and adults with cancer enrolled on immunotherapy treatment protocols in the NCI. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years
Secondary outcomes (24)
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
Measured: 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.
Incidence and treatment of HLH/MAS (now renamed IEC-HS) in patients who receive CAR-T cell therapy
Measured: 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.
Measured: 2 years
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
Measured: 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
Measured: 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
Measured: 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.
Measured: 2 years
Evaluate impact of cryopreservation on outcomes following CAR T-cell infusion
Summary of cryopreservation and patients' outcomes following CAR T-cell infusion
Measured: 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
Measured: 2 years
Evaluate absolute lymphocyte count following lymphodepleting chemotherapy
Summary of absolute lymphocyte count across lymphodepleting regimens
Measured: 2 years
Evaluate relationship between clinical variable and apheresis and manufacturing products
Summary of clinical variables and apheresis and manufacturing products
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 2 years
Evaluate cross compare responses and outcomes based on NGS MRD and FC MRD
Summary of cross compare responses and outcomes based on NGS MRD and FC MRD
Measured: 2 Years
Evaluate the role of manufacturing changes on CAR T-cell outcomes
Summary of the role of manufacturing changes on CAR T-cell outcomes
Measured: 2 Years
Evaluate the impact of clonal hematopoiesis on CAR T-cell outcomes
Summary of the impact of clonal hematopoiesis on CAR T-cell outcomes
Measured: 2 Years
Evaluate CAR T-cell related coagulopathies
Summary of CAR T-cell related coagulopathies
Measured: 2 Years
Evaluate the use of anti-cytokine therapy to treat toxicities after CAR T-cell infusion
Summary of the use of anti-cytokine therapy to treat toxicities after CAR T-cell infusion
Measured: 2 Years
Evaluate outcomes of CAR T-cells in patients with extramedullary disease
Summary of outcomes of CAR T-cells in patients with extramedullary disease
Measured: 2 Years
To evaluate outcomes of CAR T-cells based on time of infusion
Summary of outcomes of CAR T-cells based on time of infusion
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2019
- Study start23 Jan 2019
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Macrophage Activation SyndromeStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 500 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Srivandana Akshintala, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03827343
- Sponsor's protocol ID
- 999919044
- Other IDs
- 19-C-N044
- Status last verified
- 11 Jun 2026
- First submitted
- 31 Jan 2019
- Last updated
- 8 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD recorded in the medical record will be shared with intramural investigators upon request.
Publications
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.
PubMed 40953923Silbert 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.
PubMed 37486616Holland 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.
PubMed 37394115
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Retrospective Study of Immunotherapy Related Toxicities and Factors Impacting Outcomes in Children and Adults With Cancer
- ClinicalTrials.gov ID
- NCT03827343
- Acronym / sponsor ID
- 999919044
- Keywords
- CAR-T Cell Therapy, Macrophage Activation Syndrome (MAS), Hemophagocytic Lymphohistiocytosis (HLH), Natural History
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 500 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 23 Jan 2019 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 1 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –Retrospective chart review of children and adults with cancer enrolled on immunotherapy treatment protocols in the NCI. |
Who may qualify
- Ages
- 1 month to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Children and adults with cancer enrolled on immunotherapy treatment protocols in the NCI.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
Time frame: 2 years
Summary of immunotherapy related toxicity profiles and risk factors across a set of protocols in the NCI.
24 secondary outcomes
Evaluate infectious complications and their risk factors in patients who receive CAR-T cell therapy for cancer
Time frame: 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.
Time frame: 2 years
Incidence and time to resolution
Time frame: 2 years
Overall and relapse free survival
Time frame: 2 years
Incidence of end organ toxicities
Time frame: 2 years
Evaluate response and toxicity profile of second CAR T-cell infusions
Time frame: 2 years
Evaluate impact of race/ethnicity and obesity on CAR T-cell outcomes
Time frame: 2 years
Evaluate impact of cryopreservation on outcomes following CAR T-cell infusion
Time frame: 2 years
Evaluate outcomes for patients with ALL and Down Syndrome following CAR T-cell therapy
Time frame: 2 years
Evaluate absolute lymphocyte count following lymphodepleting chemotherapy
Time frame: 2 years
Evaluate relationship between clinical variable and apheresis and manufacturing products
Time frame: 2 years
Evaluate incidence of hypertension, identify risk factors for development of hypertension, summarize medical management in CAR setting, and identify complications
Time frame: 2 years
Describe baseline demographics, prior treatment characteristics and outcomes based on patients who are referred to CAR T-cell program
Time frame: 2 years
Incidence of pre-infusion BCA and use of BCA as a prognostic marker for CAR T-cell associated toxicity and efficacy
Time frame: 2 years
Presence and durability of CD72 expression in both B-ALL and normal B-ALL/hematogones
Time frame: 2 years
Evaluate interventions, documentation of care goals, and use of palliative care consultation or other symptom management
Time frame: 2 years
Evaluate long-term outcomes of survivors who received CAR T-cell therapy
Time frame: 2 years
Evaluate cross compare responses and outcomes based on NGS MRD and FC MRD
Time frame: 2 Years
Evaluate the role of manufacturing changes on CAR T-cell outcomes
Time frame: 2 Years
Evaluate the impact of clonal hematopoiesis on CAR T-cell outcomes
Time frame: 2 Years
Evaluate CAR T-cell related coagulopathies
Time frame: 2 Years
Evaluate the use of anti-cytokine therapy to treat toxicities after CAR T-cell infusion
Time frame: 2 Years
Evaluate outcomes of CAR T-cells in patients with extramedullary disease
Time frame: 2 Years
To evaluate outcomes of CAR T-cells based on time of infusion
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2026.
- Derived from this study: PubMed 40953923Culbert 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.
- Derived from this study: PubMed 37486616Silbert 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.
- Derived from this study: PubMed 37394115Holland 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.
- Individual participant dataSharing planned: Yes. All IPD recorded in the medical record will be shared with intramural investigators upon request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Srivandana Akshintala, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Macrophage Activation Syndrome and Primary Hemophagocytic Lymphohistiocytosis, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 8 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03827343, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2026.