Hematologic Malignancy, Refractory Lymphoma
Conditions
Keywords
Hematologic Malignancy, Refractory Lymphoma, CAR T cell therapy, Radiotherapy
Brief 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).
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.
Interventions
RADIATIONRadiotherapy
Radiotherapy at pre-determined dose and schedule
Sponsors
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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 * 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | Up to 2 years | 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. |
| Objective Response Rate (ORR) | Up to 2 years | 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. |
| Progression-free Survival (PFS) | Up to 2 years | 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. |
| Overall Survival | Up to 2 years | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Radiotherapy 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.
Radiotherapy: Radiotherapy at pre-determined dose and schedule | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | Radiotherapy |
|---|---|
| Age, Continuous | 79 years |
| Race/Ethnicity, Customized Caucasian | 2 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
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.
Time frame: 30 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Radiotherapy | Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0 | Grade 1 Dysgeusia | 1 Participants |
| Radiotherapy | Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0 | Grade 1 Skin hyperpigmentation | 1 Participants |
| Radiotherapy | Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0 | Grade 1 Skin ulceration | 1 Participants |
| Radiotherapy | Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0 | Grade 1 Anorexia | 1 Participants |
| Radiotherapy | Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0 | Grade 1 Neck Edema | 1 Participants |
| Radiotherapy | Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0 | Grade 1 Fatigue | 1 Participants |
| Radiotherapy | Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0 | Grade 2 dermatitis | 1 Participants |
| Radiotherapy | Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0 | Grade 1 Nausea | 1 Participants |
| Radiotherapy | Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE Version 5.0 | Total number of participants who experienced one or more RT-related toxicities, as described above | 2 Participants |
Secondary
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.
Time frame: Up to 2 years
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Radiotherapy | Duration of Response (DOR) | 7.33 months |
Secondary
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.
Time frame: Up to 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Radiotherapy | Objective Response Rate (ORR) | 3 Participants |
Secondary
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.
Time frame: Up to 2 years
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Radiotherapy | Overall Survival | 7.33 months |
Secondary
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.
Time frame: Up to 2 years
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Radiotherapy | Progression-free Survival (PFS) | 0.67 months |