Lymphocyte DepletionNCT04273893
Lymphocyte Depletion and Change in Lymphocyte Functionality
A study testing SBRT with additional treatment planning dose optimization and Blood Draws in people with Lymphocyte Depletion, run by University of Virginia at 1 site in United States.
Trial summary
Lymphocytes are a type of white blood cell (WBC) responsible for adaptive immunity. Thoracic tumors are adjacent to many blood/immune rich organs including the great vessels, heart, thoracic-spine, and lymph-node-stations. During radiation treatment the impact to lymphocytes can be significant. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphocyte Depletion
- What is being tested?
- SBRT with additional treatment planning dose optimization and Blood Draws
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Feb 2020to 1 Jun 2025
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willingness and ability to provide written informed consent and to comply with the study protocol.
- Diagnosis of biopsy confirmed non-small cell lung cancer (NSCLC) with planned treatment with SBRT as definitive therapy OR imaging confirmed lung lesion for which SBRT is planned for primary lung cancer (when clinician determines biopsy is not indicated), Registration should occur within 5 business days (before or after) of planning CT.
- Patients must decline surgery or tumor(s) must be considered to be medically inoperable
- Location and size of tumor- Participants must have either:
- peripherally located tumors (> 2 cm in all directions from the proximal bronchial tree; see Figure 2 above) as defined by RTOG 0915, OR
- centrally located tumors (tumor size ≤ 5 cm, tumors within or touching the zone of the proximal bronchial tree or adjacent to mediastinal or pericardial pleura) as defined by RTOG 0813.
Show all 13Show fewer
- Patients with recurrence of prior surgically treated lung cancers are eligible if no further surgery is planned and they otherwise meet the eligibility criteria.
- Measurable disease on chest CT, PET CT, CT simulation at diagnosis ( must be within 8 weeks of SBRT).
- Pre- radiation therapy total lymphocyte count > 0.5k/μL on blood count drawn within 2 weeks prior to registration.
- In the opinion of the treating clinician, patient is medically able to tolerate the study SBRT treatment of 50-60 Gy in 5 fractions.
- ECOG performance status of 0-2.
- Age ≥ 18 years.
- If participant is a woman of childbearing potential (WOCBP), agreement to adhere to contraception requirements from the time of consent through completion of SBRT.
Who cannot join
- Prior history of radiation therapy within 2 years of registration, however radiation therapy for skin cancer is allowed
- Systemic anti-cancer therapy within the last year prior to registration or planned use during or within 6 months following SBRT.
- Major surgery within the last 30 days before registration and/or planned before the completion of the 6 months post SBRT follow up timeframe.
- Subject is a prisoner.
- Subject is a pregnant woman.
- Patient is not medically able to tolerate the study SBRT treatment of 50-60 Gy in 5 fractions or cannot comply with other aspects of the study including serial bloodwork.
- Subject has HIV, AIDS, any type of hepatitis and/or any blood borne infectious disease for which the research lab cannot receive blood samples.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Virginia
Charlottesville, Virginia, 22908
About this study
Official title: A Pilot Randomized Study of Lymphocyte Depletion & Change in Lymphocyte Functionality During Lung Stereotactic Body Radiation (SBRT) Therapy Treatment by Selectively Reducing Irradiation of Immune Rich Organs Compared to Standard of Care Control Group
Lymphocytes are a type of white blood cell (WBC) responsible for adaptive immunity. Thoracic tumors are adjacent to many blood/immune rich organs including the great vessels, heart, thoracic-spine, and lymph-node-stations. During radiation treatment the impact to lymphocytes can be significant. This may cause a decrease in the amount of lymphocytes. A researcher at UVA has created a system to predict and reduce the immune cell reduction following lung SBRT treatments beyond standard of care. The predicted decrease in lymphocytes will be compared to the actual decrease in lymphocytes found in peripheral blood.
Researchers have found a way to give radiation that they think will result in a smaller decrease in lymphocytes after radiation. There will be two groups in this study, about half of the participants will have their radiation designed to decrease radiation to organs with a lot of blood and the other half will receive standard radiation therapy.
Participants are being asked to take part in this study because the participants have been diagnosed with NSCLC and will be receiving a type of radiation therapy called stereotactic body radiation therapy (SBRT) where high doses of radiation will be delivered to the tumor, while minimizing damage to healthy surrounding tissues.
Read the detailed description
Lymphocytes play a crucial role in the body's response to cancer by directly attacking tumors, inhibiting tumor growth and spread, and detecting and potentially eliminating emerging tumors. Tumor-infiltrating lymphocytes (TILs) are commonly found within tumors, and studies have shown that their presence is associated with more favorable outcomes. Radiation therapy (RT), particularly Stereotactic Body Radiation Therapy (SBRT), modulates the immune system by promoting the generation of Cytotoxic T Lymphocytes (CTLs) and enhancing T cell infiltration into tumors. These CTLs may eliminate distant metastases or residual disease (abscopal effect) not targeted by the primary treatment.
Lymphopenia, a known consequence of radiation therapy to virtually every part of the body, was first described in the early 20th century shortly after the discovery of X-rays. It is highly possible that irradiation of blood rich and lymphatic rich organs and bone marrow would reduce the lymphocyte counts significantly.
Additionally, recent data have suggested that lymphocyte subsets exhibit differential sensitivity to radiation, with helper CD4+ T cells being more sensitive than cytotoxic CD8+ T cells in glioblastoma (GBM) treated with RT and temozolomide, and naïve T cells more sensitive than memory T cells in prostate cancer.
Based on existing data on the effects of irradiation on total lymphocyte count and the effects on subsets of T cells, the investigators have created a lymphodepletion predictive algorithm. In this clinical trial, the investigators will test whether optimized SBRT plans lead to lower lymphocyte depletion and whether the algorithm can accurately predict lymphocyte decreases following SBRT. Optimized SBRT plans will meet all standard of care dose-volume objectives for SBRT and for the protection of organs-at-risk (OAR), but will also minimize radiation exposure to circulating blood and lymphatics, including the heart, great-vessels, lymph-node-stations, and thoracic-spine beyond what is currently optimized to reduce the integral dose to circulating blood/lymphocytes. This study will allow us to evaluate the performance of our predictive algorithm for post-SBRT decrease in lymphocyte count and to determine whether additional steps in SBRT planning will deliver lower risk of post-SBRT decreases in lymphocyte count.
- Conditions
- Lymphocyte Depletion
- Being tested
- SBRT with additional treatment planning dose optimization, SBRT with standard of care planning only, Blood Draws
- Keywords
- Lymphocyte Depletion and Change, SBRT, NSCLC, Lung Cancer, radiation therapy, non small cell, Stereotactic body radiation therapy, Treatment related lymphopenia
- Medical subject headings
- Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SBRT with additional treatment planning dose optimizationRadiation
Lung SBRT 50-60Gy in 5 fractions with standard of care planning and additional treatment planning dose optimization criteria to minimize decrease in lymphocyte count beyond dosimetric criteria from RTOG 0915/0813 SBRT trials.
SBRT with standard of care planning onlyRadiation
Lung SBRT 50-60Gy in 5 fractions with standard of care planning (no additional dose optimization beyond SOC)
Blood DrawsDiagnostic test
CBC w/ Diff and additional blood analysis for all participants in both groups. Blood draws will prior to treatment, end of treatment, 4 weeks after treatment, and 6 months after treatment.
| Study group | Role | What they receive |
|---|---|---|
| SBRT Additional treatment planning dose optimization | Experimental | Lung SBRT 50-60Gy in 5 fractions with standard of care planning and additional treatment planning dose optimization criteria to minimize decrease in lymphocyte count beyond dosimetric criteria from RTOG 0915/0813 SBRT trials. Receives: Radiation: SBRT with additional treatment planning dose optimization; Diagnostic Test: Blood Draws |
| SBRT with standard of care planning only | Active comparator | Lung SBRT 50-60Gy in 5 fractions with standard of care planning (no additional dose optimization beyond SOC) Receives: Radiation: SBRT with standard of care planning only; Diagnostic Test: Blood Draws |
What is being measured
The primary outcome is the main question the study is designed to answer.
Impact of Lymphocyte-Sparing SBRT Planning Objectives on Post-SBRT Lymphocyte Count
Mean percentage difference of measured absolute lymphocyte counts between the baseline and at each time points for the two separate arms
Measured: Baseline to End of SBRT (up to 12 days), 4 weeks after SBRT (up to 1.5 months) and 6 months after SBRT (up to 10 months)
Determine if an Algorithm Can Predict the Magnitude of Post SBRT Lymphocyte Depletion Prospectively for Participants With NSCLC
Median of the difference between predicted value and observed measurement of lymphocyte absolute counts.
Measured: Baseline to End of SBRT (up to 12 days), 4 weeks after SBRT (up to 1.5 months) and 6 months after SBRT (up to 10 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2020
- Study start12 Feb 2020
- Primary completion15 May 2023
- Study completion1 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lymphocyte DepletionStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Krishni Wijesooriya, University of Virginia
- Investigators
- Krishni Wijesooriya, PhD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04273893
- Sponsor's protocol ID
- 21718
- Other IDs
- 5R01CA234281-03
- Status last verified
- Dec 2024
- First submitted
- 12 Feb 2020
- Last updated
- 10 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wijesooriya K, Nguyen C, Conaway MR, Read PW, Romano K, Lum LG, Thakur A, Lain DW, McLaughlin CM, Luminais CK, Wood S, Williams G, Chen J, Walker B, Sprouts D, Muller D, Ward K, Dutta S, Sanders J, Cousins D, Asare E, Nesbit E, Chavis YC, Walker KV, Janowski E, Showalter T, Larner JM. First Measurement: Proactive Immune Cell Sparing in Radiation Therapy. medRxiv [Preprint]. 2025 Jan 6:2025.01.05.25320011. doi: 10.1101/2025.01.05.25320011.
PubMed 39830271
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Randomized Study of Lymphocyte Depletion & Change in Lymphocyte Functionality During Lung Stereotactic Body Radiation (SBRT) Therapy Treatment by Selectively Reducing Irradiation of Immune Rich Organs Compared to Standard of Care Control Group
- ClinicalTrials.gov ID
- NCT04273893
- Acronym / sponsor ID
- 21718
- Conditions
- Lymphocyte Depletion
- Keywords
- Lymphocyte Depletion and Change, SBRT, NSCLC, Lung Cancer, radiation therapy, non small cell, Stereotactic body radiation therapy, Treatment related lymphopenia
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 55 participants (actual)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Study start
- 12 Feb 2020 (actual)
- Primary completion
- 15 May 2023 (actual)
- Study completion
- 1 Jun 2025 (estimated)
- First posted
- 18 Feb 2020 (actual)
- Results
- Posted 10 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Lymphocytes are a type of white blood cell (WBC) responsible for adaptive immunity. Thoracic tumors are adjacent to many blood/immune rich organs including the great vessels, heart, thoracic-spine, and lymph-node-stations. During radiation treatment the impact to lymphocytes can be significant. This may cause a decrease in the amount of lymphocytes. A researcher at UVA has created a system to predict and reduce the immune cell reduction following lung SBRT treatments beyond standard of care. The predicted decrease in lymphocytes will be compared to the actual decrease in lymphocytes found in peripheral blood.
Researchers have found a way to give radiation that they think will result in a smaller decrease in lymphocytes after radiation. There will be two groups in this study, about half of the participants will have their radiation designed to decrease radiation to organs with a lot of blood and the other half will receive standard radiation therapy.
Participants are being asked to take part in this study because the participants have been diagnosed with NSCLC and will be receiving a type of radiation therapy called stereotactic body radiation therapy (SBRT) where high doses of radiation will be delivered to the tumor, while minimizing damage to healthy surrounding tissues.
Detailed description
Lymphocytes play a crucial role in the body's response to cancer by directly attacking tumors, inhibiting tumor growth and spread, and detecting and potentially eliminating emerging tumors. Tumor-infiltrating lymphocytes (TILs) are commonly found within tumors, and studies have shown that their presence is associated with more favorable outcomes. Radiation therapy (RT), particularly Stereotactic Body Radiation Therapy (SBRT), modulates the immune system by promoting the generation of Cytotoxic T Lymphocytes (CTLs) and enhancing T cell infiltration into tumors. These CTLs may eliminate distant metastases or residual disease (abscopal effect) not targeted by the primary treatment.
Lymphopenia, a known consequence of radiation therapy to virtually every part of the body, was first described in the early 20th century shortly after the discovery of X-rays. It is highly possible that irradiation of blood rich and lymphatic rich organs and bone marrow would reduce the lymphocyte counts significantly.
Additionally, recent data have suggested that lymphocyte subsets exhibit differential sensitivity to radiation, with helper CD4+ T cells being more sensitive than cytotoxic CD8+ T cells in glioblastoma (GBM) treated with RT and temozolomide, and naïve T cells more sensitive than memory T cells in prostate cancer.
Based on existing data on the effects of irradiation on total lymphocyte count and the effects on subsets of T cells, the investigators have created a lymphodepletion predictive algorithm. In this clinical trial, the investigators will test whether optimized SBRT plans lead to lower lymphocyte depletion and whether the algorithm can accurately predict lymphocyte decreases following SBRT. Optimized SBRT plans will meet all standard of care dose-volume objectives for SBRT and for the protection of organs-at-risk (OAR), but will also minimize radiation exposure to circulating blood and lymphatics, including the heart, great-vessels, lymph-node-stations, and thoracic-spine beyond what is currently optimized to reduce the integral dose to circulating blood/lymphocytes. This study will allow us to evaluate the performance of our predictive algorithm for post-SBRT decrease in lymphocyte count and to determine whether additional steps in SBRT planning will deliver lower risk of post-SBRT decreases in lymphocyte count.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SBRT Additional treatment planning dose optimization | Experimental | Radiation: SBRT with additional treatment planning dose optimization, Diagnostic Test: Blood DrawsLung SBRT 50-60Gy in 5 fractions with standard of care planning and additional treatment planning dose optimization criteria to minimize decrease in lymphocyte count beyond dosimetric criteria from RTOG 0915/0813 SBRT trials. |
| SBRT with standard of care planning only | Active comparator | Radiation: SBRT with standard of care planning only, Diagnostic Test: Blood DrawsLung SBRT 50-60Gy in 5 fractions with standard of care planning (no additional dose optimization beyond SOC) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Willingness and ability to provide written informed consent and to comply with the study protocol.
- Diagnosis of biopsy confirmed non-small cell lung cancer (NSCLC) with planned treatment with SBRT as definitive therapy OR imaging confirmed lung lesion for which SBRT is planned for primary lung cancer (when clinician determines biopsy is not indicated), Registration should occur within 5 business days (before or after) of planning CT.
- Patients must decline surgery or tumor(s) must be considered to be medically inoperable
- Location and size of tumor- Participants must have either:
- Patients with recurrence of prior surgically treated lung cancers are eligible if no further surgery is planned and they otherwise meet the eligibility criteria.
Key exclusion criteria (7 listed)
- Prior history of radiation therapy within 2 years of registration, however radiation therapy for skin cancer is allowed
- Systemic anti-cancer therapy within the last year prior to registration or planned use during or within 6 months following SBRT.
- Major surgery within the last 30 days before registration and/or planned before the completion of the 6 months post SBRT follow up timeframe.
- Subject is a prisoner.
- Subject is a pregnant woman.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SBRT with additional treatment planning dose optimizationLung SBRT 50-60Gy in 5 fractions with standard of care planning and additional treatment planning dose optimization criteria to minimize decrease in lymphocyte count beyond dosimetric criteria from RTOG 0915/0813 SBRT trials. | Radiation | SBRT Additional treatment planning dose optimization |
| SBRT with standard of care planning onlyLung SBRT 50-60Gy in 5 fractions with standard of care planning (no additional dose optimization beyond SOC) | Radiation | SBRT with standard of care planning only |
| Blood DrawsCBC w/ Diff and additional blood analysis for all participants in both groups. Blood draws will prior to treatment, end of treatment, 4 weeks after treatment, and 6 months after treatment. | Diagnostic test | SBRT Additional treatment planning dose optimization, SBRT with standard of care planning only |
Primary outcome
Impact of Lymphocyte-Sparing SBRT Planning Objectives on Post-SBRT Lymphocyte Count
Time frame: Baseline to End of SBRT (up to 12 days), 4 weeks after SBRT (up to 1.5 months) and 6 months after SBRT (up to 10 months)
Mean percentage difference of measured absolute lymphocyte counts between the baseline and at each time points for the two separate arms
Determine if an Algorithm Can Predict the Magnitude of Post SBRT Lymphocyte Depletion Prospectively for Participants With NSCLC
Time frame: Baseline to End of SBRT (up to 12 days), 4 weeks after SBRT (up to 1.5 months) and 6 months after SBRT (up to 10 months)
Median of the difference between predicted value and observed measurement of lymphocyte absolute counts.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39830271Wijesooriya K, Nguyen C, Conaway MR, Read PW, Romano K, Lum LG, Thakur A, Lain DW, McLaughlin CM, Luminais CK, Wood S, Williams G, Chen J, Walker B, Sprouts D, Muller D, Ward K, Dutta S, Sanders J, Cousins D, Asare E, Nesbit E, Chavis YC, Walker KV, Janowski E, Showalter T, Larner JM. First Measurement: Proactive Immune Cell Sparing in Radiation Therapy. medRxiv [Preprint]. 2025 Jan 6:2025.01.05.25320011. doi: 10.1101/2025.01.05.25320011.
- Individual participant dataSharing planned: No
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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.
Krishni Wijesooriya, PhD principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing SBRT with additional treatment planning dose optimization and Blood Draws in people with Lymphocyte Depletion, run by University of Virginia 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?
The sponsor lists 13 inclusion and 7 exclusion criteria. 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 10 Dec 2024. 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?
Yes. Results are posted in the registry (first posted 10 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Impact of Lymphocyte-Sparing SBRT Planning Objectives on Post-SBRT Lymphocyte Count (time frame: Baseline to End of SBRT (up to 12 days), 4 weeks after SBRT (up to 1.5 months) and 6 months after SBRT (up to 10 months)). The study lists 2 primary outcomes in all. 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 NCT04273893, which also lists 1 linked publication.
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 10 Dec 2024.