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| Name | Class |
|---|---|
| Bristol-Myers Squibb | INDUSTRY |
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The goal of this clinical trial is to learn about treatment for people with B-cell lymphoma that did not respond to treatment or that has gotten worse after treatment. The aim of this trial is to answer the following questions:
This is a pilot study to evaluate the feasibility of low-dose radiation therapy in the bridging period between chimeric antigen receptor (CAR) T-cell collection, manufacturing, and infusion (vein-to-vein) in patients with relapsed and refractory aggressive B-cell lymphoma.
Emerging cellular immunotherapies including CAR T-cell therapy have produced remarkable outcomes for this population. The Food and Drug Administration (FDA) has recently approved lisocabtagene maraleucel (liso-cel) for the management of people with relapsed and refractory B-cell lymphoma. Unfortunately, many patients undergoing liso-cel infusion will suffer progression or relapse with devastating consequences. The object of this study is to identify a novel means to enhance liso-cel activity to improve overall outcomes. The investigators hypothesize that the addition of radiation therapy targeting selected sites as bridging therapy prior to lymphodepleting chemotherapy and liso-cel infusion will be effective at improving responses for patients with relapsed and refractory B-cell lymphoma.
Results from this study will provide key justification to expand this therapeutic approach into a larger phase II clinical trial powered to examine the efficacy of this approach.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single arm | Experimental | Subjects will receive 4 gray (Gy) radiation in 2 fractions in the bridging period following lymphocyte pheresis, prior to lymphodepleting chemotherapy and chimeric antigen receptor (CAR) T-cell infusion. Post CAR T-cell infusion radiation therapy will be allowed as determined by study investigator but prespecified at time of radiation oncology consultation. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bridging radiation therapy | Radiation | Days -20 to -7: Patients will receive 2 fractions of 2 gray (Gy) for a total of 4 Gy received. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Feasibility of the intervention in the proposed study population | The percentage of subjects who receive a chimeric antigen receptor (CAR) T-cell infusion after receiving bridging radiation therapy. A one-sided Binomial test will be conducted to assess whether acceptable percentage (>70% vs <70%) of patients receive CAR T-cell perfusion after undergoing the radiation therapy. | Up to 90 days |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of treatment-emergent adverse events to assess the safety of the proposed intervention | Assessed via the incidence of combined Grade 3 and 4 cytokine release syndrome (CRS) or immune effector cell associated neurotoxicity syndrome (ICANS) events as measured by the American Society of Transplant and Cellular Therapy (ASTCT) consensus grading. The grading scale ranges from Grade 1 to 4, with a higher grade indicating a worse outcome. Assessed from the cumulative CRS and ICANS events occurring by the D+30 visit. |
| Measure | Description | Time Frame |
|---|---|---|
| Prospectively bank serum and peripheral blood mononuclear cells (PBMCs) | Storage for subsequent correlative analyses in future research. No analysis plan is provided. | Up to 270 days |
| Prospectively bank stool samples for future gut microbiome exploratory analyses |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Christopher R D'Angelo, MD | University of Nebraska | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Nebraska Medical Center | Omaha | Nebraska | 68198 | United States |
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| Liso-cel | Biological | Day 0: Patients will receive an infusion of liso-cel CAR T-cell product. Prior to the liso-cell infusion (Days -5 to -3), patients will receive lymphodepleting chemotherapy using fludarabine 30mg/m2 and cyclophosphamide 300mg/m2 per institutional standard procedures. |
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| Post-infusion radiation | Radiation | Days 30 to 80: Patients eligible for post-infusion radiation will receive a total dose of up to 32 Gy. |
|
| Up to 120 days |
| Evaluate the response to the study intervention of radiation and CAR T-cell therapy | Response rate will be assessed via PET/CT (positron emission tomography/computed tomography) using Lugano criteria. Overall response rate (ORR) will be defined as the proportion of patients with either a complete response (CR) or a partial response (PR) at D+100. For ORR, CR, and PR: two-sided exact binomial 95% confidence interval of response rate will be constructed to assess the precision of the point estimate. | Up to 190 days |
| Evaluate progression-free survival (PFS) following the study intervention | PFS will be measured using the Kaplan-Meier method. Disease progression will be measured according to clinical and imaging assessment (Lugano criteria) and will require biopsy confirmation. | Measured from first day of apheresis to death or disease progression, whichever comes first, up to two years |
| Evaluate duration of response (DOR) following CAR T-cell therapy | DOR will be summarized using the Kaplan-Meier method, but only for patients who have achieved a response of at least partial response. DOR is defined by time of first response (D+30 visit) to disease progression, start of new antineoplastic therapy due to efficacy concerns, or death from any cause. | Up to 2 years |
| Evaluate overall survival (OS) following study intervention | OS will be analyzed by the Kaplan-Meier method. Subjects alive at last follow up will be censored. | Up to 2 years |
| Evaluate the rate of prolonged cytopenias following the intervention | The rate of prolonged cytopenias will be measured as a proportion of subjects with Grade 3 or higher hematologic toxicities per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria at the D+100 visit. The 95% confidence interval will be estimated. The CTCAE v5.0 grading system ranges from Grade 0 to 5, with a higher grade indicating a worse outcome. | Up to 190 days |
| Monitor overall safety and toxicity of the intervention | Toxicity will be graded using CTCAE v5.0 guidelines. Grade 3 or higher toxicities will be tabulated using percentages at each follow up. The Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grading system ranges from Grade 0 to 5, with a higher grade indicating a worse outcome. | Up to 270 days |
| Monitor Cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) toxicity events | Cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) toxicity events will be collected for all grades as measured by American Society for Transplantation and Cellular Therapy (ASTCT) consensus criteria. The ASTCT consensus criteria grading system ranges from Grade 1 to 4, with a higher grade indicating a worse outcome. | Up to 270 days |
Sample storage at indicated timepoints. No specific analysis is intended on this protocol |
| Up to 270 days |
| Evaluate in-field versus out-of-field disease progression following radiation therapy | Proportion of individual disease sites with local progression by Lugano criteria defined by within the treated radiation field versus outside the treated radiation field | Up to 270 days |
| ID | Term |
|---|---|
| D054739 | Dendritic Cell Sarcoma, Interdigitating |
| D008224 | Lymphoma, Follicular |
| D008228 | Lymphoma, Non-Hodgkin |
| ID | Term |
|---|---|
| D015620 | Histiocytic Disorders, Malignant |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D015614 | Histiocytosis |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008223 | Lymphoma |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D000076962 | Receptors, Chimeric Antigen |
| D001336 | Automobiles |
| ID | Term |
|---|---|
| D062165 | Receptors, Artificial |
| D011956 | Receptors, Cell Surface |
| D008565 | Membrane Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011948 | Receptors, Antigen, T-Cell |
| D011946 | Receptors, Antigen |
| D011971 | Receptors, Immunologic |
| D018160 | Receptors, Cytoplasmic and Nuclear |
| D018986 | Motor Vehicles |
| D014186 | Transportation |
| D013676 | Technology, Industry, and Agriculture |
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