Enteropathy-Associated T-Cell Lymphoma, Lymphoma, Extranodal NK-T-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Large-Cell, Anaplastic, Lymphoma, T-Cell, Peripheral
Conditions
Keywords
Gray Zone Lymphoma, Immunotherapy, Peripheral T-Cell Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell lymphoma
Brief summary
Background: * Improved treatments for a variety of treatment-resistant, TNFRSF8 (CD30)-expressing malignancies including Hodgkin lymphoma, anaplastic large cell lymphoma, and other CD30- expressing lymphomas are needed. * T cells can be genetically modified to express chimeric antigen receptors (CARs) that specifically target malignancy-associated antigens. * Autologous T cells genetically modified to express CARs targeting the B-cell antigen B-lymphocyte antigen CD19 (CD19) have caused complete remissions in a small number of patients with lymphoma. These results demonstrate that CAR-expressing T cells can have anti-lymphoma activity in humans. * CD30 expression can be easily detected by immunohistochemistry on lymphoma cells, which allows selection of CD30-expressing malignancies for treatment. * CD30 is not known to be expressed by normal cells except for a small number of activated lymphocytes. * We have constructed a novel fully-human anti-CD30 CAR that can specifically recognize CD30-expressing target cells in vitro and eradicate CD30-expressing tumors in mice. * This particular CAR has not been tested before in humans. * Possible toxicities include cytokine-associated toxicities such as fever, hypotension, and neurological toxicities. Elimination of a small number of normal activated lymphocytes is possible, and unknown toxicities are also possible. Objectives: Primary -Determine the safety and feasibility of administering T-cells expressing a novel fully human anti-CD30 CAR to patients with advanced CD30-expressing lymphomas. Eligibility: * Patients must have anaplastic large cell lymphoma, peripheral T-cell lymphoma not otherwise specified, diffuse large B-cell lymphoma not otherwise specified, primary mediastinal B-cell lymphoma, grey zone lymphoma, enteropathy associated T-cell lymphoma, or extranodal natural killer (NK)/T-cell lymphoma, nasal type * Patients must have malignancy that is both measurable on a computed tomography (CT) scan with a largest diameter of at least 1.5 cm and possessing increased metabolic activity detectable by positron emission tomography (PET) scan. Alternatively, patients with lymphoma detected by flow cytometry of bone marrow are eligible. * Patients must have a creatinine of 1.6 mg/dL or less and a normal cardiac ejection fraction. * An Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 is required. * No active infections are allowed including evidence of active human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. At the time of protocol enrollment patients must be seronegative for cytomegalovirus (CMV) by antibody testing or must have a negative blood CMV polymerase chain reaction (PCR). * Absolute neutrophil count greater than or equal to 1000/micro L, platelet count greater than or equal to 55,000/micro L, hemoglobin greater than or equal to 8g/dL * Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less or equal to 3 times the upper limit of the institutional normal unless liver involvement by malignancy is demonstrated. * At least 14 days must elapse between the time of any prior systemic treatment (including corticosteroids above 5 mg/day of prednisone or equivalent corticosteroid dose) and initiation of required leukapheresis. * Clear CD30 expression must be detected on 75% or more of malignant cells from either bone marrow or lymphoma mass by flow cytometry or immunohistochemistry. The patient s malignancy will need to be assessed for CD30 expression by flow cytometry or immunohistochemistry performed at the National Institutes of Health (NIH). If unstained, paraffin-embedded bone marrow or lymphoma sections are available from prior biopsies, these can be used to determine CD30 expression by immunohistochemistry; otherwise, patients will need to come to the NIH for a biopsy to determine CD30 expression. The sample for CD30 expression can come from a biopsy obtained at any time before enrollment, unless the patient has received a prior anti-CD30 monoclonal antibody, in which case the sample must come from a biopsy following completion of the most recent anti-CD30 monoclonal antibody treatment. * Eligible patients with diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma must have received 2 prior treatment regimens at least 1 of which included an anthracycline and an anti-CD20 monoclonal antibody. * Patients who have never had an allogeneic hematopoietic stem cell transplant as well as patients who have had a 9/10 or 10/10 human leukocyte antigen (HLA)-matched sibling or a 9/10 or 10/10 HLA- matched unrelated donor hematopoietic stem cell transplant are potentially eligible. * Women who are pregnant or plan to become pregnant will be excluded.
Detailed description
Background: * Improved treatments for a variety of treatment-resistant, TNFRSF8 (CD30)-expressing malignancies including Hodgkin lymphoma, anaplastic large cell lymphoma, and other CD30- expressing lymphomas are needed. * T cells can be genetically modified to express chimeric antigen receptors (CARs) that specifically target malignancy-associated antigens. * Autologous T cells genetically modified to express CARs targeting the B-cell antigen B-lymphocyte antigen CD19 (CD19) have caused complete remissions in a small number of patients with lymphoma. These results demonstrate that CAR-expressing T cells can have anti-lymphoma activity in humans. * CD30 expression can be easily detected by immunohistochemistry on lymphoma cells, which allows selection of CD30-expressing malignancies for treatment. * CD30 is not known to be expressed by normal cells except for a small number of activated lymphocytes. * We have constructed a novel fully-human anti-CD30 CAR that can specifically recognize CD30-expressing target cells in vitro and eradicate CD30-expressing tumors in mice. * This particular CAR has not been tested before in humans. * Possible toxicities include cytokine-associated toxicities such as fever, hypotension, and neurological toxicities. Elimination of a small number of normal activated lymphocytes is possible, and unknown toxicities are also possible. Objectives: Primary -Determine the safety and feasibility of administering T-cells expressing a novel fully-human anti-CD30 CAR to patients with advanced CD30-expressing lymphomas. Eligibility: * Patients must have anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma not otherwise specified, diffuse large B-cell lymphoma not otherwise specified, primary mediastinal B-cell lymphoma, grey zone lymphoma, enteropathy-associated T-cell lymphoma, or extranodal natural killer (NK)//T-cell lymphoma, nasal type * Patients must have malignancy that is both measurable on a computed tomography (CT) scan with a largest diameter of at least 1.5 cm and possessing increased metabolic activity detectable by positron emission tomography (PET) scan. Alternatively, patients with lymphoma detected by flow cytometry of bone marrow are eligible. * Patients must have a creatinine of 1.6 mg/dL or less and a normal cardiac ejection fraction. * An Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 is required. * No active infections are allowed including evidence of active human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. At the time of protocol enrollment, patients must be seronegative for cytomegalovirus (CMV) by antibody testing or must have a negative blood CMV polymerase chain reaction (PCR). * Absolute neutrophil count greater than or equal to 1000/micro L, platelet count greater than or equal to 55,000/micro L, hemoglobin greater than or equal to 8g/dL * Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less or equal to 3 times the upper limit of the institutional normal unless liver involvement by malignancy is demonstrated. * At least 14 days must elapse between the time of any prior systemic treatment (including corticosteroids above 5 mg/day of prednisone or equivalent corticosteroid dose) and initiation of required leukapheresis. * Clear CD30 expression must be detected on 75% or more of malignant cells from either bone marrow or lymphoma mass by flow cytometry or immunohistochemistry. The patient s malignancy will need to be assessed for CD30 expression by flow cytometry or immunohistochemistry performed at the National Institutes of Health (NIH). If unstained, paraffin-embedded bone marrow or lymphoma sections are available from prior biopsies, these can be used to determine CD30 expression by immunohistochemistry; otherwise, patients will need to come to the NIH for a biopsy to determine CD30 expression. The sample for CD30 expression can come from a biopsy obtained at any time before enrollment, unless the patient has received a prior anti-CD30 monoclonal antibody, in which case the sample must come from a biopsy following completion of the most recent anti-CD30 monoclonal antibody treatment. * Eligible patients with diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma must have received 2 prior treatment regimens at least 1 of which included an anthracycline and an anti-CD20 monoclonal antibody. * Patients who have never had an allogeneic hematopoietic stem cell transplant as well as patients who have had a 9/10 or 10/10 human leukocyte antigen (HLA)-matched sibling or a 9/10 or 10/10 HLA- matched unrelated donor hematopoietic stem cell transplant are potentially eligible. * Women who are pregnant or plan to become pregnant will be excluded. Design: * This is a phase I dose-escalation trial. * Patients will undergo leukapheresis. * T cells obtained by leukapheresis will be genetically modified to express an anti-CD30 CAR. * Patients will receive a lymphocyte-depleting chemotherapy conditioning regimen with the intent of enhancing the activity of the infused anti-CD30 CAR-expressing T cells. * A chemotherapy conditioning regimen of cyclophosphamide and fludarabine will be administered prior to all CAR T-Cell infusions. Fludarabine will be given on the same days as the cyclophosphamide. * Two days after the chemotherapy ends, patients will receive an infusion of anti-CD30-CAR-expressing T cells. * The initial dose level of this dose-escalation trial will be 0.3x10(6) CAR+ T cells/kg of recipient bodyweight for Cohort 1. The initial dose level will be 1 x 10 (6) CAR+T cells/kg for Cohort 2. * The cell dose administered will be escalated until a maximum tolerated dose is determined. * Following the T-cell infusion, there is a mandatory 9-day inpatient hospitalization to monitor for toxicity. * Outpatient follow-up is planned for 2 weeks and 1, 2, 3, 4, 6, 9, and 12 months after the CAR T-cell infusion. Long-term gene-therapy follow-up consisting of yearly visits to a doctor near the patients home for 4 more years and then yearly telephone contact for 10 additional years will be required. * As of Amendment E (Protocol version: 08/03/2018), repeat treatments consisting of the conditioning chemotherapy followed by a CAR T-cell infusion at the maximum tolerated dose (MTD) for the patients cohort are allowed for eligible patients with any best responses except continuing complete remission or progressive malignancy. * Re-enrollment will be allowed for a small number of subjects.
Interventions
BIOLOGICALAnti-Tumor Necrosis Factor (TNF) Receptor Superfamily Member 8 (CD30) Chimeric Antigen Receptor (CAR) T cells
Dose-escalation trial starting dose: 0.3x10\^6 Chimeric Antigen Receptor (CAR)+ T cells/kg (weight based dosing) (up to a maximum dose of 18x10\^6 CAR+ T cells/kg) infuse on day 0
DRUGCyclophosphamide
300 or 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3
DRUGFludarabine
30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 73 Years
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA: Malignancy Criteria: * Patients must have anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma not otherwise specified, diffuse large B-cell lymphoma not otherwise specified, primary mediastinal B-cell lymphoma, grey zone lymphoma, enteropathy-associated T-cell lymphoma, or extranodal natural killer (NK)/T-cell lymphoma, nasal type * Clear TNFRSF8 (CD30) expression must be detected on 75% or more of malignant cells from either bone marrow or lymphoma mass by flow cytometry or immunohistochemistry. The patient's malignancy will need to be assessed for CD30 expression by flow cytometry or immunohistochemistry performed at the National Institutes of Health (NIH). If unstained, paraffin-embedded bone marrow or lymphoma sections are available from prior biopsies, these can be used to determine CD30 expression by immunohistochemistry; otherwise, patients will need to come to the NIH for a biopsy to determine CD30 expression. The sample for CD30 expression can come from a biopsy obtained at any time before enrollment, unless the patient has received a prior anti-CD30 monoclonal antibody, in which case the sample must come from a biopsy following completion of the most recent anti-CD30 monoclonal antibody treatment. * Eligible patients with diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma must have received 2 prior treatment regimens at least 1 of which included an anthracycline and an anti-B-lymphocyte antigen CD20 (CD20) monoclonal antibody. * Patients must have measurable malignancy as defined by at least one of the criteria below. * Lymphoma mass that is measurable (minimum 1.5 cm in largest diameter) by computed tomography (CT) scan is required unless bone marrow lymphoma is detectable. * For a lymphoma mass to count as measurable malignancy, it must have abnormally increased metabolic activity when assessed by positron emission tomography (PET) scan. * For lymphoma with only bone marrow involvement, no mass is necessary, but if a mass is not present, bone marrow malignancy must be detectable by flow cytometry. Other Inclusion Criteria: * Greater than or equal to 18 years of age and less than or equal to age 73. * Able to understand and sign the Informed Consent Document. * Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0-2 * Room air oxygen saturation of 92% or greater * Male patients and must be willing to practice birth control from the time of enrollment on this study and for four months following the final CAR T-cell infusion. Pre-menopausal patients (female patients who have had a menstrual period within the last year) must be willing to practice birth control from the time of enrollment and for one year following the final CAR T cell infusion. * Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune -competence and thus are less responsive to the experimental treatment and more susceptible to its toxicities.) * Seronegative for Human T-cell lymphotropic virus type 1 (HTLV-1). * Negative for hepatitis B surface antigen. Positive hepatitis B tests can be further evaluated by confirmatory tests; and if confirmatory tests are negative, the patient can be enrolled. * Seronegative for hepatitis C antibody unless antigen negative. If hepatitis C antibody test is positive, then patients must be tested for the presence of ribonucleic acid (RNA) by Reverse transcription polymerase chain reaction (RT-PCR) and be Hepatitis C (HCV) RNA negative to be enrolled. * A patient with a prior history of hepatitis B or a prior history of hepatitis C may participate, as long as the patient s viral hepatitis has been treated, and the patient has no detectable Hepatitis B (HBV) deoxyribonucleic acid (DNA) or HCV RNA. * At time of protocol enrollment, the patient should be negative for cytomegalovirus (CMV) by antibody testing or by PCR. In case of disagreement between these 2 CMV tests, the tests will be repeated, and Dept. of Laboratory Medicine consulted. * Absolute neutrophil count greater than or equal to 1000/mm\^3 without the support of filgrastim or other growth factors. * Platelet count greater than or equal to 55,000/mm\^3 * Hemoglobin greater than 8.0 g/dl. Transfusion support is allowed. * Less than 5% malignant cells in the peripheral blood leukocytes * Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less or equal to 3 times the upper limit of the institutional normal unless liver involvement by malignancy is demonstrated. * Serum creatinine less than or equal to 1.6 mg/dL. * Total bilirubin less than or equal to 2.0 mg/dl. * At least 14 days must have elapsed since any prior systemic therapy prior to apheresis and prior to the initiation of chemotherapy (including systemic corticosteroids at doses greater than prednisone 5 mg/day or the equivalent corticosteroid doses). Because this protocol requires collection of autologous blood cells by leukapheresis in order to prepare CAR T cells, systemic anti-malignancy therapy including systemic corticosteroid therapy at doses greater than prednisone 5 mg/day or the equivalent corticosteroid doses is not allowed within 14 days prior to the required leukapheresis. NOTE: Because of the long half-life and potential to affect CAR T-cells, 30 days must elapse from the time of administration of anti-Programmed cell death protein 1 (PD-1) or anti-Programmed death-ligand 1 (PD-L1) antibodies or other agents that in the opinion of the PI can stimulate immune activity and infusion of CAR T-cells. * Normal cardiac ejection fraction (greater than or equal to 50% by echocardiography) and no evidence of hemodynamically significant pericardial effusion as determined by an echocardiogram within 4 weeks of the start of the treatment protocol. * Patients must not take corticosteroids at doses higher than 5 mg/day of prednisone or the equivalent for 14 days before apheresis, and for 14 days prior to the conditioning chemotherapy regimen. * Patients must be willing to undergo endotracheal intubation, mechanical ventilation, dialysis, cardiopulmonary resuscitation (CPR), and electrical defibrillation. Patients must be willing to receive vasopressor drugs and all other standard intensive care unit interventions. Any living will must be amended to allow these interventions, or the patient will not eligible. * Patients who have been treated on other protocols of genetically-modified T-cells at the National Institutes of Health (NIH) only are potentially eligible under these conditions: * At least 6 months have elapsed since the last genetically-modified T-cell therapy that the patient received and there is no evidence of replication-competent retroviruses (evidence must be provided from prior NIH gene-therapy protocol Principal Investigator) and persisting genetically-modified T cells are not detectable in the patient's blood (evidence must be provided by prior NIH gene-therapy protocol Principal Investigator). Additional Inclusion Criteria Pertinent Only for Patients with Prior Allogeneic Transplantation: * Recipients must have received an 9/10 or 10/10 HLA-matched sibling allogeneic hematopoietic stem cell transplant, or a 9/10 or 10/10 HLA-matched unrelated donor (URD) allo-HSCT for an eligible CD30+ lymphoma. * Donor T cell engraftment after allo-Hematopoietic stem-cell transplantation (HSCT)(\>90% donor chimerism of the T-cell compartment). * Patients must be at least 90 days post-transplant. * Patients must be off all systemic immunosuppressive drugs including corticosteroids at doses of greater than 5 mg/day prednisone or equivalent, if given for treatment of graft versus host disease, for at least 28 days prior to protocol enrollment and must remain off immunosuppressive drugs while enrolled on the protocol. Patients must not be taking any systemic steroids at doses greater than 5 mg/day prednisone or equivalent at all for 14 days prior to apheresis and initiation of chemotherapy. Topical corticosteroid preparations applied to the skin such as solutions, creams, and ointments are allowed. Inhaled corticosteroids are allowed, and corticosteroid eye drops are allowed. * Prior donor lymphocyte infusions (DLIs) are not necessary. * Either no evidence of graft versus host (GVHD) or minimal clinical evidence of acute GVHD and chronic GVHD while off of systemic immunosuppressive therapy for at least 28 days. Minimal clinical evidence of acute GVHD defined as grade 0 to I acute GVHD 109 Minimal evidence of chronic GVHD is defined as mild global score chronic GVHD (as defined by the 2005 NIH consensus project) or no chronic GVHD .107 Subjects with disease that is controlled to stage I acute GVHD or to mild global score chronic GVHD with local topical cutaneous steroids will be eligible for enrollment.
Exclusion criteria
* Patients with Hodgkin lymphoma are no longer eligible for participation (as of amendment G, Protocol version: 08/12/2019). * Patients that require urgent therapy due to tumor mass effects or spinal cord compression. * Patients with lymphoma masses 10.0 cm or larger in longest diameter will not be eligible. * Patients that have active hemolytic anemia. * Patients who are currently taking any medications for systemic anticoagulation other than aspirin will not be eligible. * Patients with second malignancies in addition to their lymphoma are not eligible if the second malignancy has required treatment (including maintenance therapy) within the past 4 years or is not in complete remission. There are two exceptions to this criterion: successfully treated non-metastatic basal cell or squamous cell skin carcinoma. * Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Women of child-bearing potential are defined as all women except women who are postmenopausal or who have had a hysterectomy. Postmenopausal will be defined as women over the age of 55 who have not had a menstrual period in at least 1 year. * Active uncontrolled systemic infections (defined as infections causing fevers and infections requiring intravenous antibiotics when the intravenous antibiotics have been administered for less than 72 hours); active coagulation disorders or other major uncontrolled medical illnesses of the cardiovascular, respiratory, endocrine, renal, gastrointestinal, genitourinary or immune system; history of myocardial infarction; history of idiopathic ventricular tachycardia or ventricular fibrillation in the past 12 months or history of ventricular tachycardia or ventricular fibrillation (VT/VF) associated with VT/VF risk factors (e.g., QT prolongation and cardiomyopathy); active cardiac arrhythmias (Active atrial fibrillation is not allowed, but resolved atrial fibrillation is allowed.); active obstructive or restrictive pulmonary disease; or active autoimmune diseases such as rheumatoid arthritis. * Patients will not be seen for screening appointments or enrolled on the protocol if they have been hospitalized within the 7 days prior to the screening appointment or the date of protocol enrollment. * Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease) , unless the immunodeficiency has been cured by allogeneic stem cell transplant. * Systemic corticosteroid therapy at doses greater than 5 mg/day of prednisone or the equivalent dose is not allowed within 14 days prior to the required leukapheresis, or the initiation of the conditioning chemotherapy regimen. Corticosteroid creams, ointments, and eye drops are allowed. * History of severe immediate hypersensitivity reaction to any of the agents used in this study. * Patients with current central nervous system (CNS) involvement by malignancy (either by imaging or cerebrospinal fluid involvement or biopsy-proven). * Patients currently taking anticoagulants.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose of Anti-Tumor Necrosis Factor (TNF) Receptor Superfamily Member 8 (CD30) Chimeric Antigen Receptor (CAR) in Participants With Advanced CD30-expressing Lymphomas | 4-5 weeks after first dose | Maximum tolerated dose is defined as the dose at which a maximum of 1 of 6 participants has a dose-limiting toxicity (DLT). A DLT is defined as toxicities occurring within 30 days of CAR T-cell infusion. DLT's are Grade 3 or Grade 4 toxicities possibly, probably, or definitely related to either the anti-CD30 CAR T cells or the fludarabine and cyclophosphamide chemotherapy conditioning regimen and lasting more than 7 days. A DLT will only be considered in participants who have received CAR T-cell infusions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | From time of infusion until 1 month after infusion | Peak percentage and the percentage 1 month after infusion of peripheral blood mononuclear cells (PBMC) that expressed the Chimeric Antigen Receptor (CAR) T-cells assessed by polymerase chain reaction (PCR). |
| Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response | Responses will be assessed as long as the patient is on-study at the following time-points: 1, 2, 3, 4, 6, 9, and 12 months after CAR T-cell infusion. Then responses were assessed every 6 months up until 3 years after CAR T-cell infusion. | Response was measured using the Cheson et al. Revised Response Criteria for Malignant Lymphoma, Journal of Clinical Oncology 2007 and Recommendations for Initial Evaluation, Staging, and Response Assessment of Non-Hodgkin Lymphoma: The Lugano Classification Journal of Clinical Oncology, 2014). Complete Response (CR) is complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. Partial Response (PR) is ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. Progressive Disease (PD) ≥ 50% increase from nadir in the sum of the products of at least two lymph nodes, or appearance of a new lesion greater than 1.5 cm in any axis even if other lesions are decreasing in size. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | Date treatment consent signed to date off study, approximately 11 months and 26 days, 7 months and 10 days, 39 months and 7 days, 17 months and 3 days, 6 months and 15 days, and 1 month and 7 days for each group respectively. | Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. |
| Number of Participants With a Dose Limiting Toxicity (DLT) | 30 days within CAR T-cell infusion | A DLT is defined as toxicities occurring within 30 days of CAR T-cell infusion. DLT's are Grade 3 or Grade 4 toxicities possibly, probably, or definitely related to either the anti-CD30 CAR T cells or the fludarabine and cyclophosphamide chemotherapy conditioning regimen and lasting more than 7 days. A DLT will only be considered in participants who have received CAR T-cell infusions. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose Escalation Cohort 1 Dose Level 1 - 0.3x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg Participants who have not had an allogeneic hematopoietic stem cell transplant. 0.3x10\^6 Chimeric Antigen Receptor (CAR) T cells per kg of recipient bodyweight
Starting dose: 0.3x10\^6 Chimeric Antigen Receptor (CAR)+ T cells/kg (weight based dosing) infuse on day 0 and Cyclophosphamide: 300 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 and Fludarabine: 30 mg/m\^2 IV infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3 | 3 |
| Dose Escalation Cohort 1 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg Participants who have not had an allogeneic hematopoietic stem cell transplant. 1.0x10\^6 Chimeric Antigen Receptor (CAR) T cells per kg of recipient bodyweight
1.0x10\^6 Chimeric Antigen Receptor (CAR)+ T cells/kg (weight based dosing) infuse on day 0 and Cyclophosphamide: 300 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 and Fludarabine: 30 mg/m\^2 IV infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3 | 3 |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg Participants who have not had an allogeneic hematopoietic stem cell transplant. 3.0x10\^6 Chimeric Antigen Receptor (CAR) T cells per kg of recipient bodyweight
3.0x10\^6 Chimeric Antigen Receptor (CAR)+ T cells/kg (weight based dosing) infuse on day 0 and Cyclophosphamide: This chemotherapy dose was changed part-way through the protocol, thus 4 participants received 500 mg/m\^2 and 3 participants received 300 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 and Fludarabine: 30 mg/m\^2 IV infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3. | 7 |
| Dose Escalation Cohort 1 Dose Level 4 - 9.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg Participants who have not had an allogeneic hematopoietic stem cell transplant. 9.0x10\^6 Chimeric Antigen Receptor (CAR) T cells per kg of recipient bodyweight
9.0x10\^6 Chimeric Antigen Receptor (CAR)+ T cells/kg (weight based dosing) infuse on day 0 and Cyclophosphamide: 500 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 and Fludarabine: 30 mg/m\^2 IV infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3 | 5 |
| Dose Escalation Cohort 2 Dose Level 1 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg Participants who have had an Human Leukocyte Antigen (HLA)-matched sibling or an 8/8-HLA-matched unrelated donor transplant.
1.0x10\^6 Chimeric Antigen Receptor (CAR) T cells per kg of recipient bodyweight
1.0 x10\^6 Chimeric Antigen Receptor (CAR)+ T cells/kg (weight based dosing) infuse on day 0 and Cyclophosphamide: 300 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 and Fludarabine: 30 mg/m\^2 IV infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3 | 3 |
| Dose Escalation Cohort 2 Dose Level 2 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg Participants who have had an Human Leukocyte Antigen (HLA)-matched sibling or an 8/8 HLA-matched unrelated donor transplant.
3.0x10\^6 Chimeric Antigen Receptor (CAR) T cells per kg of recipient bodyweight
3.0x10\^6 Chimeric Antigen Receptor (CAR)+ T cells/kg (weight based dosing) infuse on day 0 and Cyclophosphamide: 300 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 and Fludarabine: 30 mg/m\^2 IV infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3 | 1 |
| Cohort 1 No Level Assigned - Enrolled But Not Treated Participants in this group were enrolled but not treated. | 1 |
| Cohort 2 No Level Assigned - Enrolled But Not Treated Participants in this group were enrolled but not treated. | 1 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Chemotherapy was started and not finished & no Chimeric Antigen Receptor T-cells were administered. | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Did not receive treatment. | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Enrolled and removed from study with no treatment | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Dose Escalation Cohort 1 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Dose Escalation Cohort 1 Dose Level 4 - 9.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Dose Escalation Cohort 2 Dose Level 1 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Dose Escalation Cohort 2 Dose Level 2 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Cohort 1 No Level Assigned - Enrolled But Not Treated | Dose Escalation Cohort 1 Dose Level 1 - 0.3x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Cohort 2 No Level Assigned - Enrolled But Not Treated | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 7 Participants | 5 Participants | 3 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 24 Participants |
| Age, Continuous | 42.97 years STANDARD_DEVIATION 9.59 | 39.87 years STANDARD_DEVIATION 14.8 | 27.94 years STANDARD_DEVIATION 13.63 | 28.9 years STANDARD_DEVIATION 7.29 | 43.8 years STANDARD_DEVIATION 0 | 31.4 years STANDARD_DEVIATION 0 | 36.13 years STANDARD_DEVIATION 6.49 | 26.1 years STANDARD_DEVIATION 0 | 36.17 years STANDARD_DEVIATION 12.02 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 7 Participants | 5 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 3 Participants | 6 Participants | 4 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 20 Participants |
| Region of Enrollment United States | 3 participants | 7 participants | 5 participants | 3 participants | 1 participants | 1 participants | 3 participants | 1 participants | 24 participants |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 8 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 4 Participants | 3 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 7 | 0 / 5 | 0 / 3 | 0 / 1 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 7 / 7 | 5 / 5 | 3 / 3 | 1 / 1 |
| serious Total, serious adverse events | 0 / 3 | 1 / 3 | 5 / 7 | 3 / 5 | 0 / 3 | 1 / 1 |
Outcome results
Primary
Maximum Tolerated Dose of Anti-Tumor Necrosis Factor (TNF) Receptor Superfamily Member 8 (CD30) Chimeric Antigen Receptor (CAR) in Participants With Advanced CD30-expressing Lymphomas
Maximum tolerated dose is defined as the dose at which a maximum of 1 of 6 participants has a dose-limiting toxicity (DLT). A DLT is defined as toxicities occurring within 30 days of CAR T-cell infusion. DLT's are Grade 3 or Grade 4 toxicities possibly, probably, or definitely related to either the anti-CD30 CAR T cells or the fludarabine and cyclophosphamide chemotherapy conditioning regimen and lasting more than 7 days. A DLT will only be considered in participants who have received CAR T-cell infusions.
Time frame: 4-5 weeks after first dose
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Maximum Tolerated Dose of Anti-Tumor Necrosis Factor (TNF) Receptor Superfamily Member 8 (CD30) Chimeric Antigen Receptor (CAR) in Participants With Advanced CD30-expressing Lymphomas | 3 million CAR T-cells/kg |
Secondary
Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response
Response was measured using the Cheson et al. Revised Response Criteria for Malignant Lymphoma, Journal of Clinical Oncology 2007 and Recommendations for Initial Evaluation, Staging, and Response Assessment of Non-Hodgkin Lymphoma: The Lugano Classification Journal of Clinical Oncology, 2014). Complete Response (CR) is complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. Partial Response (PR) is ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. Progressive Disease (PD) ≥ 50% increase from nadir in the sum of the products of at least two lymph nodes, or appearance of a new lesion greater than 1.5 cm in any axis even if other lesions are decreasing in size. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time frame: Responses will be assessed as long as the patient is on-study at the following time-points: 1, 2, 3, 4, 6, 9, and 12 months after CAR T-cell infusion. Then responses were assessed every 6 months up until 3 years after CAR T-cell infusion.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Participants | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response | Complete Response | 0 Participants |
| All Participants | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response | Partial Response | 2 Participants |
| All Participants | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response | Stable Disease | 1 Participants |
| All Participants | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response | Progressive Disease | 0 Participants |
| Dose Escalation Cohort 1 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response | Stable Disease | 2 Participants |
| Dose Escalation Cohort 1 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response | Partial Response | 0 Participants |
| Dose Escalation Cohort 1 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response | Complete Response | 1 Participants |
| Dose Escalation Cohort 1 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response | Progressive Disease | 0 Participants |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response | Progressive Disease | 0 Participants |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response | Stable Disease | 4 Participants |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response | Partial Response | 3 Participants |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response | Complete Response | 0 Participants |
| Dose Escalation Cohort 1 Dose Level 4 - 9.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response | Complete Response | 0 Participants |
| Dose Escalation Cohort 1 Dose Level 4 - 9.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response | Progressive Disease | 1 Participants |
| Dose Escalation Cohort 1 Dose Level 4 - 9.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response | Partial Response | 2 Participants |
| Dose Escalation Cohort 1 Dose Level 4 - 9.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response | Stable Disease | 2 Participants |
| Dose Escalation Cohort 2 Dose Level 1 - 0.3x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response | Stable Disease | 2 Participants |
| Dose Escalation Cohort 2 Dose Level 1 - 0.3x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response | Progressive Disease | 0 Participants |
| Dose Escalation Cohort 2 Dose Level 1 - 0.3x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response | Partial Response | 1 Participants |
| Dose Escalation Cohort 2 Dose Level 1 - 0.3x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response | Complete Response | 0 Participants |
| Dose Escalation Cohort 2 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response | Partial Response | NA Participants |
| Dose Escalation Cohort 2 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response | Stable Disease | NA Participants |
| Dose Escalation Cohort 2 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response | Progressive Disease | NA Participants |
| Dose Escalation Cohort 2 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response | Complete Response | NA Participants |
Secondary
Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells
Peak percentage and the percentage 1 month after infusion of peripheral blood mononuclear cells (PBMC) that expressed the Chimeric Antigen Receptor (CAR) T-cells assessed by polymerase chain reaction (PCR).
Time frame: From time of infusion until 1 month after infusion
Population: Participants #8, and 23 were not assigned to a dose level since they didn't receive chemo or cells. Participant # 5 first enrolled as #3 did not result in cell infusion and was re-enrolled with a new number for cell infusion. This is the same for #18 who was first enrolled as #16.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #4 - Peak percentage of CAR+ cells among peripheral blood mononuclear cells | 0.257878064 peak percentage |
| All Participants | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #4 - %CAR+ cells among peripheral blood mononuclear cells 1 month after infusion | NA peak percentage |
| All Participants | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #2 - %CAR+ cells among peripheral blood mononuclear cells 1 month after infusion | NA peak percentage |
| All Participants | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #1 - %CAR+ cells among peripheral blood mononuclear cells 1 month after infusion | NA peak percentage |
| All Participants | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #1 - Peak percentage of CAR+ cells among peripheral blood mononuclear cells | 2.505994998 peak percentage |
| All Participants | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #2 - Peak percentage of CAR+ cells among peripheral blood mononuclear cells | 1.003513397 peak percentage |
| Dose Escalation Cohort 1 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #5 - Peak percentage of CAR+ cells among peripheral blood mononuclear cells | 5.692026394 peak percentage |
| Dose Escalation Cohort 1 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #6 - Peak percentage of CAR+ cells among peripheral blood mononuclear cells | 0.066168665 peak percentage |
| Dose Escalation Cohort 1 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #5 - %CAR+ cells among peripheral blood mononuclear cells 1 month after infusion | 0.036582556 peak percentage |
| Dose Escalation Cohort 1 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #7 - Peak percentage of CAR+ cells among peripheral blood mononuclear cells | 0.875579553 peak percentage |
| Dose Escalation Cohort 1 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #7 - %CAR+ cells among peripheral blood mononuclear cells 1 month after infusion | 0.002843526 peak percentage |
| Dose Escalation Cohort 1 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #6 - %CAR+ cells among peripheral blood mononuclear cells 1 month after infusion | 0.010607229 peak percentage |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #14 - %CAR+ cells among peripheral blood mononuclear cells 1 month after infusion | 2.361884069 peak percentage |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #11 - Peak percentage of CAR+ cells among peripheral blood mononuclear cells | 25.06555951 peak percentage |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #12 - Peak percentage of CAR+ cells among peripheral blood mononuclear cells | 2.061723582 peak percentage |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #13 - Peak percentage of CAR+ cells among peripheral blood mononuclear cells | 0.951813793 peak percentage |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant 14 - Peak percentage of CAR+ cells among peripheral blood mononuclear cells | 3.770199852 peak percentage |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #15 - Peak percentage of CAR+ cells among peripheral blood mononuclear cells | 21.6416809 peak percentage |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #18 - Peak percentage of CAR+ cells among peripheral blood mononuclear cells | 6.193353177 peak percentage |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #26 - Peak percentage of CAR+ cells among peripheral blood mononuclear cells | 25.56426658 peak percentage |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #11 - %CAR+ cells among peripheral blood mononuclear cells 1 month after infusion | NA peak percentage |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #12 - %CAR+ cells among peripheral blood mononuclear cells 1 month after infusion | 2.061723582 peak percentage |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #13 - %CAR+ cells among peripheral blood mononuclear cells 1 month after infusion | NA peak percentage |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #15 - %CAR+ cells among peripheral blood mononuclear cells 1 month after infusion | 1.584343701 peak percentage |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #18 - %CAR+ cells among peripheral blood mononuclear cells 1 month after infusion | 6.193353177 peak percentage |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #26 - %CAR+ cells among peripheral blood mononuclear cells 1 month after infusion | NA peak percentage |
| Dose Escalation Cohort 1 Dose Level 4 - 9.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #25 - %CAR+ cells among peripheral blood mononuclear cells 1 month after infusion | 18.33580648 peak percentage |
| Dose Escalation Cohort 1 Dose Level 4 - 9.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #22 - Peak percentage of CAR+ cells among peripheral blood mononuclear cells | 29.40752103 peak percentage |
| Dose Escalation Cohort 1 Dose Level 4 - 9.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #24 - Peak percentage of CAR+ cells among peripheral blood mononuclear cells | 22.45790377 peak percentage |
| Dose Escalation Cohort 1 Dose Level 4 - 9.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #20 - Peak percentage of CAR+ cells among peripheral blood mononuclear cells | 3.484185735 peak percentage |
| Dose Escalation Cohort 1 Dose Level 4 - 9.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #21 - Peak percentage of CAR+ cells among peripheral blood mononuclear cells | 51.30355798 peak percentage |
| Dose Escalation Cohort 1 Dose Level 4 - 9.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #21 - %CAR+ cells among peripheral blood mononuclear cells 1 month after infusion | 8.51303351 peak percentage |
| Dose Escalation Cohort 1 Dose Level 4 - 9.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #22 - %CAR+ cells among peripheral blood mononuclear cells 1 month after infusion | 11.65873475 peak percentage |
| Dose Escalation Cohort 1 Dose Level 4 - 9.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #25 - Peak percentage of CAR+ cells among peripheral blood mononuclear cells | 55.04760657 peak percentage |
| Dose Escalation Cohort 1 Dose Level 4 - 9.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #24 - %CAR+ cells among peripheral blood mononuclear cells 1 month after infusion | 0.289276145 peak percentage |
| Dose Escalation Cohort 1 Dose Level 4 - 9.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #20 - %CAR+ cells among peripheral blood mononuclear cells 1 month after infusion | 1.110480727 peak percentage |
| Dose Escalation Cohort 2 Dose Level 1 - 0.3x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #17 - Peak percentage of CAR+ cells among peripheral blood mononuclear cells | 9.701843954 peak percentage |
| Dose Escalation Cohort 2 Dose Level 1 - 0.3x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #9 - Peak percentage of CAR+ cells among peripheral blood mononuclear cells | 10.425784436 peak percentage |
| Dose Escalation Cohort 2 Dose Level 1 - 0.3x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #9 - %CAR+ cells among peripheral blood mononuclear cells 1 month after infusion | 0.145937491 peak percentage |
| Dose Escalation Cohort 2 Dose Level 1 - 0.3x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | #10 - %CAR+ cells among peripheral blood mononuclear cells 1 month after infusion | 0.006382466 peak percentage |
| Dose Escalation Cohort 2 Dose Level 1 - 0.3x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #17 - %CAR+ cells among peripheral blood mononuclear cells 1 month after infusion | 0.09701347 peak percentage |
| Dose Escalation Cohort 2 Dose Level 1 - 0.3x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant 10 - Peak percentage of CAR+ cells among peripheral blood mononuclear cells | 1.173870125 peak percentage |
| Dose Escalation Cohort 2 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participant #19 - Peak percentage of CAR+ cells among peripheral blood mononuclear cells | NA peak percentage |
| Dose Escalation Cohort 2 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells | Participants #19 - %CAR+ cells among peripheral blood mononuclear cells 1 month after infusion | NA peak percentage |
Other Pre-specified
Number of Participants With a Dose Limiting Toxicity (DLT)
A DLT is defined as toxicities occurring within 30 days of CAR T-cell infusion. DLT's are Grade 3 or Grade 4 toxicities possibly, probably, or definitely related to either the anti-CD30 CAR T cells or the fludarabine and cyclophosphamide chemotherapy conditioning regimen and lasting more than 7 days. A DLT will only be considered in participants who have received CAR T-cell infusions.
Time frame: 30 days within CAR T-cell infusion
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| All Participants | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 3 definitely related | 0 Participants |
| All Participants | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 3 possibly related | 0 Participants |
| All Participants | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 4 definitely related | 0 Participants |
| All Participants | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 3 probably related | 0 Participants |
| All Participants | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 4 probably related | 0 Participants |
| All Participants | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 4 possibly related | 0 Participants |
| Dose Escalation Cohort 1 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 4 probably related | 0 Participants |
| Dose Escalation Cohort 1 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 3 definitely related | 0 Participants |
| Dose Escalation Cohort 1 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 3 possibly related | 0 Participants |
| Dose Escalation Cohort 1 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 4 possibly related | 0 Participants |
| Dose Escalation Cohort 1 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 4 definitely related | 0 Participants |
| Dose Escalation Cohort 1 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 3 probably related | 0 Participants |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 3 probably related | 0 Participants |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 3 possibly related | 0 Participants |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 3 definitely related | 0 Participants |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 4 possibly related | 0 Participants |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 4 probably related | 0 Participants |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 4 definitely related | 0 Participants |
| Dose Escalation Cohort 1 Dose Level 4 - 9.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 4 possibly related | 1 Participants |
| Dose Escalation Cohort 1 Dose Level 4 - 9.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 3 possibly related | 0 Participants |
| Dose Escalation Cohort 1 Dose Level 4 - 9.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 3 definitely related | 0 Participants |
| Dose Escalation Cohort 1 Dose Level 4 - 9.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 3 probably related | 0 Participants |
| Dose Escalation Cohort 1 Dose Level 4 - 9.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 4 definitely related | 0 Participants |
| Dose Escalation Cohort 1 Dose Level 4 - 9.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 4 probably related | 1 Participants |
| Dose Escalation Cohort 2 Dose Level 1 - 0.3x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 3 possibly related | 0 Participants |
| Dose Escalation Cohort 2 Dose Level 1 - 0.3x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 4 probably related | 0 Participants |
| Dose Escalation Cohort 2 Dose Level 1 - 0.3x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 4 possibly related | 0 Participants |
| Dose Escalation Cohort 2 Dose Level 1 - 0.3x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 4 definitely related | 0 Participants |
| Dose Escalation Cohort 2 Dose Level 1 - 0.3x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 3 definitely related | 0 Participants |
| Dose Escalation Cohort 2 Dose Level 1 - 0.3x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 3 probably related | 0 Participants |
| Dose Escalation Cohort 2 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 3 definitely related | 0 Participants |
| Dose Escalation Cohort 2 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 4 possibly related | 0 Participants |
| Dose Escalation Cohort 2 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 3 possibly related | 0 Participants |
| Dose Escalation Cohort 2 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 4 probably related | 0 Participants |
| Dose Escalation Cohort 2 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 4 definitely related | 0 Participants |
| Dose Escalation Cohort 2 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With a Dose Limiting Toxicity (DLT) | Grade 3 probably related | 0 Participants |
Other Pre-specified
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time frame: Date treatment consent signed to date off study, approximately 11 months and 26 days, 7 months and 10 days, 39 months and 7 days, 17 months and 3 days, 6 months and 15 days, and 1 month and 7 days for each group respectively.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Participants | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | 3 Participants |
| Dose Escalation Cohort 1 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | 3 Participants |
| Dose Escalation Cohort 1 Dose Level 3 - 3.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | 7 Participants |
| Dose Escalation Cohort 1 Dose Level 4 - 9.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | 5 Participants |
| Dose Escalation Cohort 2 Dose Level 1 - 0.3x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | 3 Participants |
| Dose Escalation Cohort 2 Dose Level 2 - 1.0x10^6 Chimeric Antigen Receptor (CAR) T Cells Per kg | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) | 1 Participants |