Hematologic MalignancyNCT04473937

Radiation Post-CAR T in Refractory Lymphoma

A study testing Radiotherapy in people with Hematologic Malignancy and Refractory Lymphoma, run by Massachusetts General Hospital at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

This study is evaluating the safety and efficacy of using radiotherapy in participants who have refractory lymphoma shortly after receiving CAR T cell therapy (axicel or tisacel). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Hematologic Malignancy, Refractory Lymphoma
What is being tested?: Radiotherapy
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 3 participants
Where: 1 siteUnited States
Study dates: 5 Jan 2021to 3 Jul 2023
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

Patients must be able to undergo biopsy. Biopsy will be obtained for patients to exclude possibility of false negative residual FDG avidity on PET/CT that is not substantially increased relative to pre-CAR-T PET/CT. Exceptions are allowed for patients who have clearly progressive disease for whom delaying radiation therapy to obtain a biopsy may worsen outcome (such as cases of cord compression), and for patients for whom the risks of biopsy are high (such as patients with evidence for CNS involvement).
Biopsy-confirmed refractory disease within 30-90 days following commercial axicabtagene ciloleucel or tisagenlecleucel therapy for a hematologic malignancy (these include relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma). Of note, 'refractory' refers to patients who had early refractory disease after CAR-T cell therapy and not to patients who have received CAR-T for refractory disease, but had complete response to CAR-T cell therapy.
At least 1 measurable lesion according to the Lugano criteria1. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy
The following criteria pertain to pattern of progression:
Patients may have one refractory lesion without other residual or progressive disease as per PET/CT
Patients may have more than one refractory lesion, but with evidence for at least partial response of at least one other lesion as per PET/CT

Show all 13Show fewer

Patients with more than one site of refractory disease without evidence for at least partial response of at least one other lesion are eligible if they are:
A. Symptomatic from a refractory lesion (such as cord compression or focal pain) or
B. Have disease that can locally affect the spinal canal or brain if left untreated.
Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for clinically non-significant toxicities such as alopecia and prolonged cytopenias that are not expected to worsen during RT) if there is concern for overlap of anticipated radiation-related toxicity and toxicity from prior therapy due to where the RT field is located.
Age 18 or older
Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2.
Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

Any medical condition likely to interfere with assessment of safety or efficacy of RT
Patients with more than one site of disease without any evidence for response to CAR T cell therapy who are not focally symptomatic due to progressive disease or do not have disease that can locally affect the spinal canal or brain if left untreated
Women of child-bearing potential who are pregnant because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential.
In the investigators judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.

Trial locations and contacts

1 site in 1 country.

United States1 site

Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114

Other trials in United States

About this study

Official title: Radiation Therapy To Enhance CAR T Efficacy Early in Post-CAR T Cell Therapy Refractory Lymphoma: A Pilot Study

This study is evaluating the safety and efficacy of using radiotherapy in participants who have refractory lymphoma shortly after receiving CAR T cell therapy (axicel or tisacel).

Read the detailed description

This research study is a Pilot Study, which is the first time investigators are examining this intervention after administration of CAR T cell therapy. This research study looks to systematically investigate the safety and efficacy of radiotherapy following CAR T cell therapy (axicel or tisacel) in refractory lymphoma. CAR T cell therapy involves genetically modifying T cells to target tumor cells for death. Radiotherapy is a standard treatment offered with refractory lymphoma and uses high-energy x rays, or particles, to destroy or damage cancer cells. Few have received CAR T cell therapy prior to radiation therapy and this study aims to gather more information on radiotherapy following CAR T cell therapy as a treatment option and its potential to improve participants immune system's response to cancer cells as well as its interaction with CAR T cell therapy to better treat refractory lymphoma.

The research study procedures include screening for eligibility, enrollment, biopsy following radiation, post-treatment period, and long-term follow-up.

Participants will receive radiotherapy at a dose and schedule determined by the study doctor.
Participants will be followed for up to 24 months after completion of study treatment.

It is expected that about 20 people will take part in this research study.

Conditions: Hematologic Malignancy, Refractory Lymphoma
Being tested: Radiotherapy
Keywords: Hematologic Malignancy, Refractory Lymphoma, CAR T cell therapy, Radiotherapy
Medical subject headings: Hematologic Neoplasms, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RadiotherapyRadiation
Radiotherapy at pre-determined dose and schedule

Study groups in NCT04473937
Study group	Role	What they receive
Radiotherapy	Experimental	Participants must have received CAR-T infusion within the last 90 days prior to completing a study screening and enrollment process. * Participants will be enrolled within 28 days after screening is complete and radiotherapy will occur within 14 days after study enrollment. * Radiotherapy will be administered based on a dose and schedule pre-determined by the study doctor. Receives: Radiation: Radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0
Rate and severity of radiotherapy-related toxicity as per CTCAE v5.0 (Common Terminology Criteria for Adverse Events) during radiotherapy (RT) or within the first 30 days of completing RT. The number of participants who experienced radiotherapy-related toxicities are listed below.
Measured: 30 days

Secondary outcomes (4)

Duration of Response (DOR)
DOR is defined as the length of time between a subject's first objective response per Lugano criteria (complete response or partial response) and local disease progression per Lugano criteria, or death regardless of cause.
Measured: Up to 2 years
Objective Response Rate (ORR)
ORR is defined as the incidence of either a complete response or a partial response by Lugano criteria. All subjects that do not meet the criteria for an objective response by the analysis data cutoff date will be considered non-responders.
Measured: Up to 2 years
Progression-free Survival (PFS)
PFS is defined as the time from radiotherapy completion date to the date of disease progression per Lugano criteria or death from any cause. Subjects not meeting the criteria for progression by the analysis data cutoff date will be censored at their last evaluable disease assessment date.
Measured: Up to 2 years
Overall Survival
Overall survival is defined as the time from radiotherapy completion to the date of death. Subjects who have not died by the analysis cutoff date will be censored at their last contact date.
Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Jan 20213 Jul 2023

First posted16 Jul 2020
Study start5 Jan 2021
Primary completion9 Oct 2021
Study completion3 Jul 2023

Why it stopped: Futility

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.
Other trials for Hematologic MalignancyStudies of the same condition, open and under way.
More trials run by Massachusetts General HospitalThe 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: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 3 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04473937
Sponsor's protocol ID: 19-861
Status last verified: Sep 2025
First submitted: 13 Jul 2020
Last updated: 24 Sep 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: Yes
Individual data sharing: Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Hematologic Malignancy trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Radiation Therapy To Enhance CAR T Efficacy Early in Post-CAR T Cell Therapy Refractory Lymphoma: A Pilot Study
ClinicalTrials.gov ID: NCT04473937
Acronym / sponsor ID: 19-861
Conditions: Hematologic Malignancy, Refractory Lymphoma
Keywords: Hematologic Malignancy, Refractory Lymphoma, CAR T cell therapy, Radiotherapy
Study type: Interventional
Recruitment status: TerminatedReason stopped: Futility
Enrolment: 3 participants (actual)
Lead sponsor: Massachusetts General HospitalUniversity, hospital or other
Study start: 5 Jan 2021 (actual)
Primary completion: 9 Oct 2021 (actual)
Study completion: 3 Jul 2023 (actual)
First posted: 16 Jul 2020 (actual)
Results: Posted 10 Apr 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study is evaluating the safety and efficacy of using radiotherapy in participants who have refractory lymphoma shortly after receiving CAR T cell therapy (axicel or tisacel).

Detailed description

The research study procedures include screening for eligibility, enrollment, biopsy following radiation, post-treatment period, and long-term follow-up.

Participants will receive radiotherapy at a dose and schedule determined by the study doctor.
Participants will be followed for up to 24 months after completion of study treatment.

It is expected that about 20 people will take part in this research study.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Radiotherapy	Experimental	Radiation: RadiotherapyParticipants must have received CAR-T infusion within the last 90 days prior to completing a study screening and enrollment process. * Participants will be enrolled within 28 days after screening is complete and radiotherapy will occur within 14 days after study enrollment. * Radiotherapy will be administered based on a dose and schedule pre-determined by the study doctor.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

Patients must be able to undergo biopsy. Biopsy will be obtained for patients to exclude possibility of false negative residual FDG avidity on PET/CT that is not substantially increased relative to pre-CAR-T PET/CT. Exceptions are allowed for patients who have clearly progressive disease for whom delaying radiation therapy to obtain a biopsy may worsen outcome (such as cases of cord compression), and for patients for whom the risks of biopsy are high (such as patients with evidence for CNS involvement).
Biopsy-confirmed refractory disease within 30-90 days following commercial axicabtagene ciloleucel or tisagenlecleucel therapy for a hematologic malignancy (these include relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma). Of note, 'refractory' refers to patients who had early refractory disease after CAR-T cell therapy and not to patients who have received CAR-T for refractory disease, but had complete response to CAR-T cell therapy.
At least 1 measurable lesion according to the Lugano criteria1. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy
The following criteria pertain to pattern of progression:
Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for clinically non-significant toxicities such as alopecia and prolonged cytopenias that are not expected to worsen during RT) if there is concern for overlap of anticipated radiation-related toxicity and toxicity from prior therapy due to where the RT field is located.

Key exclusion criteria (4 listed)

Any medical condition likely to interfere with assessment of safety or efficacy of RT
Patients with more than one site of disease without any evidence for response to CAR T cell therapy who are not focally symptomatic due to progressive disease or do not have disease that can locally affect the spinal canal or brain if left untreated
Women of child-bearing potential who are pregnant because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential.
In the investigators judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.

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
RadiotherapyRadiotherapy at pre-determined dose and schedule	Radiation	Radiotherapy

Primary outcome

Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0
Time frame: 30 days
Rate and severity of radiotherapy-related toxicity as per CTCAE v5.0 (Common Terminology Criteria for Adverse Events) during radiotherapy (RT) or within the first 30 days of completing RT. The number of participants who experienced radiotherapy-related toxicities are listed below.

4 secondary outcomes

Duration of Response (DOR)
Time frame: Up to 2 years
Objective Response Rate (ORR)
Time frame: Up to 2 years
Progression-free Survival (PFS)
Time frame: Up to 2 years
Overall Survival
Time frame: Up to 2 years

Results and safety

Results posted to the registry on 10 Apr 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Radiotherapy	3	3

Primary outcome: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0

Time frame: 30 days. Count of participants. Unit: Participants

Measure	Radiotherapy n = 3
Grade 2 dermatitis	1
Grade 1 Dysgeusia	1
Grade 1 Skin hyperpigmentation	1
Grade 1 Skin ulceration	1
Grade 1 Anorexia	1
Grade 1 Neck Edema	1
Grade 1 Fatigue	1
Grade 1 Nausea	1

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: All adverse events are reported from enrollment through 3 months after radiation therapy. After 3 months, targeted adverse events (neurological, hematological, infections, autoimmune disorders, and secondary malignancies) are reported for 6 months after treatment with axicel or tisacel or until disease progression, whichever occurs first. All cause mortality was monitored for up to two years.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Radiotherapy	0 of 3 (0%)	3 of 3 (100%)	3 of 3

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

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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.

Chirayu G Patel, MD, MPH principal investigator

Massachusetts General Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Radiotherapy in people with Hematologic Malignancy and Refractory Lymphoma, run by Massachusetts General Hospital 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 4 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: stopped early, as of the sponsor's last update on 24 Sep 2025. 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 Apr 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?

Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0 (time frame: 30 days). 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 NCT04473937.

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 24 Sep 2025.