Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Non-Hodgkin
Conditions
Keywords
Pediatric, JCAR017, CAR-T, CART, CD19, ALL, NHL, DLBCL, BL, PMBCL, Cell Therapy, LisoCell, Young Adults, Lymphoproliferative disorders, Immune system diseases, Leukemia, Lymphoma, lymphatic diseases
Brief summary
This is a Phase 1/2, open-label, single arm, multicohort study to evaluate the safety and efficacy of JCAR017 in pediatric subjects aged ≤ 25 years with CD19+ r/r B-ALL and B-NHL. Phase 1 will identify a recommended Phase 2 dose (RP2D). Phase 2 will evaluate the efficacy of JCAR017 RP2D in the following three disease cohorts: Cohort 1 (r/r B-ALL), Cohort 2 (MRD+ B-ALL) and Cohort 3 (r/r B-NHL, \[DLBCL, BL, or PMBCL\]). A Simon's Optimal two-stage study design will be applied to Cohort 1 and 2 in Phase 2.
Detailed description
This is a Phase 1/2, open-label, single arm, multicohort study incorporating Simon's Optimal two-stage design to evaluate the safety and efficacy of JCAR017 in pediatric subjects aged ≤ 25 years with CD19+ r/r B-ALL and B-NHL. In the Phase 1, up to 5 dose levels will be of JCAR017 will be evaluated. Enrollment will commence in pediatric subjects with r/r B-ALL at Dose Level 1 (DL1) of 0.05x10\^6 CAR+ T cells/kg (maximum DL1 of 5x10\^6 JCAR017 CAR+ T cells \[non-weight adjusted\]). If this dose is confirmed to be safe and tolerable, additional subjects will be enrolled at higher dose(s) up to 0.75 x10\^6 CAR+ T cells/kg (maximum of 75x10\^6 JCAR017 CAR+ T cells \[non-weight adjusted\]) with the aim to identify the RP2D. Dose escalation/de-escalation will follow a modified toxicity probability interval (mTPI-2) algorithm. A Safety Review Committee (SRC) will recommend the Phase 2 dose (defined as RP2D) based on an integrated assessment of the safety, PK and preliminary efficacy information from at least 10 pediatric subjects treated at the RP2D. In Phase 2, a minimum of 71 additional subjects (\< 18 years of age) will be enrolled into one of the 3 cohorts listed below. The sample size for Cohorts 1 and 2 is calculated according to Simon's Optimal two-stage design. The 10 or more pediatric subjects treated at the RP2D in Phase 1 will form part of the sample size (ie, Cohort 1 and Cohort 2). Therefore, the protocol intends to treat 81 primary endpoint evaluable pediatric subjects in Phase 2, if warranted by the evaluation of results at the completion of the first stage of the study in each cohort. * Cohort 1 (r/r B-ALL): 48 evaluable pediatric subjects (13 subjects in Stage 1 and 35 in Stage 2) * Cohort 2 (MRD+ B-ALL): 23 evaluable pediatric subjects (9 subjects in Stage 1 and 14 subjects in Stage 2) * Cohort 3 (r/r B-NHL \[DLBCL, BL, or PMBCL\]): 10 evaluable pediatric subjects. Due to the very low incidence rate and therefore expected low subject accrual, there is no formal sample size for this arm. Up to 20 additional B-ALL subjects between 18 and 25 years of age may be enrolled in Phase 2. Following treatment with JCAR017 subjects will then enter the post-treatment period for disease progression/relapse, safety, CAR T cell persistence, and survival up to 24 months after administration of JCAR017. Efficacy will be assessed both locally and by an Independent Review Committee. Response assessments will be based on bone marrow and blood morphologic criteria, physical examination findings, along with laboratory assessments of cerebral spinal fluid (CSF) and bone marrow MRD (B-ALL only) assessments. B-NHL subjects will also have radiographic disease assessment by CT/MRI scans and tumor biopsies, if accessible. Post-study follow-up for survival, relapse, long-term toxicity, and lentiviral vector safety will continue under a separate long-term follow-up protocol for up to 15 years after the JCAR017 infusion as per health authority regulatory guidelines. An Independent Data Monitoring Committee will monitor the study conduct.
Interventions
DRUGJCAR017
JCAR017
DRUGLymphodepleting
Lymphodepleting
DRUGFludarabine
Fludarabine
DRUGCyclophosphamide
Cyclophosphamide
Sponsors
Celgene
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 25 Years
Healthy volunteers
No
Inclusion criteria
Subjects must satisfy the following criteria to be enrolled in the study: 1. Phase 1: Subject \< 18 years of age and weighs ≥ 6 kg at the time of signing the informed consent form (ICF)/informed assent form (IAF). Phase 2: Subject ≤ 25 years of age and weighs ≥ 6 kg at the time of signing the ICF/IAF. 2. Subject (when applicable, parental/legal representative) must understand and voluntarily provide permission to the ICF/IAF prior to conducting any study-related assessments/procedures. 3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements. 4. Investigator considers the subject is appropriate for adoptive T cell therapy. 5. Evidence of CD19 expression via flow cytometry (peripheral blood or bone marrow) or immunohistochemistry (bone marrow biopsy) 6. Subject has a Karnofsky score of ≥ 50 (subjects ≥ 16 years of age) or a Lansky score ≥ 50 (subjects \< 16 years of age). 7. Diagnosis of B-cell ALL or B-cell NHL as defined below: Phase 1: Subjects with r/r B-ALL, defined as morphological evidence of disease in BM (5% or greater lymphoblast by morphology) and either of the following: * First or greater marrow relapse, or * Any marrow relapse after allogeneic HSCT, or * Primary refractory defined as not achieving a CR or a CRi after 2 or more separate induction regimens (or chemo-refractory as not achieving CR/CRi after 1 cycle of standard chemotherapy for relapsed leukemia), or * Ineligible for allogeneic HSCT Note: Subjects will be included regardless of MRD status. Phase 2: Subjects with one of the following: * Cohort 1: r/r B-ALL, defined as morphological evidence of disease in BM (5% or greater lymphoblast by morphology) and either: * First or greater marrow relapse, or * Any marrow relapse after allogeneic HSCT, or * Primary refractory defined as not achieving a CR or a CRi after 2 or more separate induction regimens (or chemo-refractory as not achieving CR/CRi after 1 cycle of standard chemotherapy for relapsed leukemia), or * Ineligible for allogeneic HSCT. * Cohort 2: MRD+ B-ALL, defined as: * \< 5% lymphoblasts by morphology with, * MRD detected by a validated assay at a frequency of 1 x10-4 or greater in BM cells. Subjects eligible for enrollment in Cohort 2 are those with MRD positive morphologic CR2 after re-induction when these subjects had previously experienced an early relapse (\< 36 months) after first-line chemotherapy. Subjects who are in MRD+ morphologic CR3 and later, regardless of time to relapse in earlier lines, are also eligible. Subjects who are in morphologic relapse at screening (r/r B-ALL) and become MRD+ after bridging chemotherapy are also eligible for treatment in Cohort 2. * Cohort 3: r/r B-NHL (DLBCL, BL or PMBCL), defined as measurable disease after 1 or more lines of chemotherapy and/or having failed HSCT or being ineligible for HSCT. Note: B-NHL subjects with secondary CNS lymphoma involvement are eligible however subject selection must consider clinical risk factors for severe neurological AEs and alternative treatment options. Subjects should only be enrolled if the Investigator considers the potential benefit outweighs the risk for the subject. 8. Subjects with Philadelphia chromosome positive ALL are eligible if they are intolerant to or have failed one or more lines of tyrosine-kinase inhibitor (TKI) therapy or if TKI therapy is contraindicated. 9. Adequate organ function, defined as: * Adequate BM function to receive LD chemotherapy as assessed by the Investigator. * Subject with adequate renal function, which is defined as: Serum creatinine based on age/gender as described below. Subjects that do not meet the criteria but who have a creatinine clearance or radioisotope glomerular filtration rate (GFR) \> 70 mL/min/1.73 m2 are eligible.• Alanine aminotransferase (ALT) ≤ 5 x upper limit of normal (ULN) and total bilirubin \< 2.0 mg/dL (or \< 3.0 mg/dL for subjects with Gilbert's syndrome or leukemic/lymphomatous infiltration of the liver). * Adequate pulmonary function, defined as ≤ Grade 1 dyspnea according to Common Toxicity Criteria for Adverse Events (CTCAE) and oxygen saturation (SaO2) ≥ 92% on room air. * Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) ≥ 40% as assessed by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) within 4 weeks prior to leukapheresis. 10. Adequate vascular access for leukapheresis procedure. 11. Participants must agree to use effective contraception
Exclusion criteria
The presence of any of the following will exclude a subject from enrollment: 1. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study. 2. Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study. 3. Subject has any condition that confounds the ability to interpret data from the study. 4. Subject with a history of another primary malignancy that has not been in remission for at least 2 years prior to enrollment. 5. Subjects who have received previous CD19-targeted therapy must have CD19-positive disease confirmed since completing the prior CD19-targeted therapy. 6. Prior CAR T cell or other genetically-modified T cell therapy. 7. Subject with a previous history of or active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection. 8. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment at the time of leukapheresis or JCAR017 infusion. 9. Subject has presence of acute or chronic graft-versus-host disease (GVHD). 10. Subject with active autoimmune disease requiring immunosuppressive therapy. 11. Subject has cardiac disorders (CTCAE version 4.03 Grade 3 or 4) within the past 6 months. 12. Subject with a concomitant genetic syndrome, with the exception of Down's syndrome. 13. Subject with active CNS disease and significant neurological deterioration. Subjects with CNS-2 or CNS-3 involvement are eligible provided they are asymptomatic and do not have significant neurological deterioration and, in the opinion of the study investigator, the CNS disease burden can be controlled until JCAR017 infusion. 14. Subject with a history or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, cerebral edema, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis. 15. Subject is pregnant or nursing. 16. Subject has used the following: * Therapeutic doses of corticosteroids (defined as \> 0.4 mg/kg maximum 20 mg/day prednisone or equivalent) within 7 days prior to leukapheresis or 72 hours prior to JCAR017 infusion. Physiologic replacement, topical, and inhaled steroids are permitted. * Low-dose chemotherapy (eg, vincristine, rituximab, cyclophosphamide ≤ 300 mg/m2) given after leukapheresis to maintain disease control must be stopped ≥ 7 days prior to LD chemotherapy. * Cytotoxic chemotherapeutic agents that are not considered lymphotoxic within 1 week prior to leukapheresis. Oral anticancer agents are allowed if at least 3 half-lives have elapsed prior to leukapheresis. * Lymphotoxic chemotherapeutic agents (eg, cyclophosphamide, ifosfamide, bendamustine) within 2 weeks prior to leukapheresis. * Experimental agents within 4 weeks prior to leukapheresis unless no response or PD is documented on the experimental therapy and at least 3 half-lives have elapsed prior to leukapheresis. * Immunosuppressive therapies within 4 weeks prior to leukapheresis and JCAR017 infusion (eg, calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as antitumor necrosis factor \[TNF\], anti-IL-6, or anti-IL-6R). * Donor lymphocyte infusions (DLI) within 6 weeks prior to JCAR017 infusion. * Radiation within 6 weeks prior to leukapheresis. Subjects must have PD in irradiated lesions or have additional non-irradiated lesions to be eligible. Radiation to a single lesion, if additional non-irradiated, measurable lesions are present, is allowed up to 2 weeks prior to leukapheresis. * Allogeneic HSCT within 90 days prior to leukapheresis. 17. Tumor invasion of venous or arterial vessels (B-NHL subjects only). 18. Deep Venous Thrombosis (DVT) or Pulmonary Embolism (PE) within 3 months prior to leukapheresis. Subjects with DVT or PE that occurred longer than 3 months prior to leukapheresis, who still require ongoing therapeutic levels of anti-coagulation therapy, are also excluded. 19. Existence of CD19-negative clone(s) of leukemia cells
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events up to 30 Days Post JCAR017 Infusion | From first JCAR017 infusion (Day 1) to 30 days after JCAR017 infusion | An AE is defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. Treatment Emergent Adverse Events (TEAEs) are defined as any AE occurring or worsening on the day of the JCAR017 infusion until 30 days post-treatment (JCAR017 infusion) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or greater. |
| Number of Participants With Dose Limiting Toxicities | From first JCAR017 infusion (Day 1) to 28 days after JCAR017 infusion | A DLT was defined as: * Death not related to disease progression * Grade (Gr) 4 (Life-threatening) neurotoxicity * Gr 3 (Severe) neurotoxicity of greater than 7 days * Gr 3 neurotoxicity does not revert to baseline within 28 days of the start date of the Grade 3 event * Seizures of grade that do not resolve within 7 days * Gr 4 cytokine release syndrome (CRS) that does not resolve to Grade ≤ 3 within 3 days * Gr 3 CRS that does not resolve to Grade ≤ 2 within 7 days * Any increase in aspartate aminotransferase (AST) or ALT \> 3 × ULN and concurrent increase in total bilirubin \> 2 × ULN that is unrelated to CRS and has no other probable reason to explain the combination of increases * Any cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary, or neurologic Gr 3 or 4 event not pre-existing or not due to the underlying malignancy * Any other Gr 3 or 4 event deemed unexpected by the Investigator and considered a DLT upon evaluation by the safety review committee |
| Concentration of JCAR017 in Peripheral Blood at Day 28 Post JCAR017 Infusion | At day 28 post JCAR017 infusion | Concentration of JCAR017 in Peripheral Blood was assessed by droplet digital polymerase chain reaction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils/Leukocytes; Eosinophils/Leukocytes; Lymphocytes/Leukocytes; Neutrophils/Leukocytes; Monocytes/Leukocytes | Baseline and at Day 28 | Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy. |
| Change From Baseline at Day 28 in Hematology Laboratory Parameters- Erythrocytes | Baseline and at Day 28 | Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy. |
| Change From Baseline at Day 28 in Hematology Laboratory Parameters- Hematocrit | Baseline and at Day 28 | Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy. |
| Change From Baseline at Day 28 in Hematology Laboratory Parameters- Hemoglobin | Baseline and at Day 28 | Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy. |
| Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Alanine Aminotransferase; Alkaline Phosphatase; Aspartate Aminotransferase; Lactate Dehydrogenase | Baseline and at Day 28 | Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy. |
| Change From Baseline at Day 28 in Laboratory Parameters- Albumin; Protein | Baseline and at Day 28 | Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy. |
| Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Baseline and at Day 28 | Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy. |
| Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bilirubin; Creatinine; Direct Bilirubin; Urate | Baseline and at Day 28 | Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy. |
| Number of Participants With Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion | From first JCAR017 infusion (Day 1) to 90 days after JCAR017 infusion | An AE is defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. Treatment Emergent Adverse Events (TEAEs) are defined as any AE occurring or worsening on the day of the JCAR017 infusion until 90 days post-treatment (JCAR017 infusion) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or greater. The following scale for grading was used - Grade 3 = Severe, Grade 4 = Life-Threatening. |
| Overall Response Rate (ORR) | Up to Day 56 | ORR is defined as the percentage of participants who achieved either a complete response (CR) or complete response with incomplete blood recovery (CRi) on Day 28 that is confirmed on Day 56. Response assessment was performed according to the 2019 Comprehensive Cancer Network (NCCN) response criteria guidelines for pediatric acute lymphoblastic leukemia (ALL). CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. CRi is defined as meeting all criteria for CR except platelets \< 100,000/μL or ANC is \< 1000/μL. |
| Duration of Response (DOR) | From first response (either CR or CRi) until progressive disease (PD), disease relapse, or death from any cause, whichever occurs first (Up to approximately 14 months) | DOR is defined as time from first response (either CR or CRi) until progressive disease (PD), disease relapse, or death from any cause, whichever occurs first. Response assessment was performed according to the 2019 Comprehensive Cancer Network (NCCN) response criteria guidelines for pediatric ALL. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. CRi is defined as meeting all criteria for CR except platelets \< 100,000/μL or ANC is \< 1000/μL. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease. |
| Relapse Free Survival (RFS) | Up to approximately 15 months | RFS is defined as time from conforming JCAR017 infusion to the first progressive disease (PD), relapsed disease or death from any cause, whichever occurs first. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease. Relapsed disease is defined as Reappearance of blasts in the blood or bone marrow (\> 5%) or \> 1% with previous/supportive molecular findings or in any extramedullary site after a CR. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. |
| Event Free Survival (EFS) | From conforming JCAR017 infusion to PD, relapsed disease, start of a new anticancer therapy including Hematopoietic Stem Cell Transplant (HSCT) or death from any cause, whichever occurs first (Up to approximately 15 months) | EFS is defined as time from conforming JCAR017 infusion to progressive disease (PD), relapsed disease, start of a new anticancer therapy including HSCT or death from any cause, whichever occurs first. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease. Relapsed disease is defined as Reappearance of blasts in the blood or bone marrow (\> 5%) or \> 1% with previous/supportive molecular findings or in any extramedullary site after a CR. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. Only responders are included in he analysis. Censored participants were also analyzed. |
| Overall Survival (OS) | From the date of first confirming JCAR017 infusion to the date of death due to any reason (Up to approximately 24 months) | OS is defined as the interval from the date of first confirming JCAR017 infusion to the date of death due to any reason. |
| Minimal Residual Response (MRD) Negative Response Rate | Up to Day 56 | Minimal Residual Disease (MRD) Negative Response Rate is defined as the percentage of participants achieving either a CR or CRi with a MRD negative bone marrow on Day 28, confirmed on Day 56. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. CRi is defined as meeting all criteria for CR except platelets \< 100,000/μL or ANC is \< 1000/μL. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease. Disease assessments recorded on or after start of a new anticancer therapy, including HSCT, will not be considered, nor will disease assessments reported after a PD or relapse has been observed. |
| Number of Participants Who Achieved a Response After JCAR017 Infusion and Then Proceeded to Hematopoietic Stem Cell Transplant | Up to approximately 24 months | Number of participants who undergo HSCT after receiving a JCAR017 infusion and achieving a response are presented. The time of proceeding to HSCT is defined as the time of commencing the conditioning regimen as required for HSCT. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. CRi is defined as meeting all criteria for CR except platelets \< 100,000/μL or ANC is \< 1000/μL. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease. |
| Number of Participants With Manufacturing Success of JCAR017 Product | From screening to JCAR017 infusion (day -35 to day 1) | Successful product was defined as JCAR017 product was generated and able to be QC released (including nonconforming product) for infusion. Unsuccessful product is defined as no JCAR017 product could be generated after two manufacturing attempts using a single apheresis product for starting material or product was unable to be QC released for infusion. |
| Number of Participants With Serious Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion | From first JCAR017 infusion (Day 1) to 90 days after JCAR017 infusion | Serious adverse events (SAE) are defined as any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/ birth defect; constitutes an important medical event. Treatment Emergent Adverse Events (TEAEs) are defined as any AE occurring or worsening on the day of the JCAR017 infusion until 90 days post-treatment (JCAR017 infusion) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or greater. |
| Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Baseline and at Day 28 | Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy. |
Countries
France, Germany, Italy, Netherlands, Spain, United States
Participant flow
Pre-assignment details
The study was terminated and hence participants were not enrolled in Phase 2 cohorts (r/r B-ALL; MRD+ B-ALL; r/r B-NHL).
Participants by arm
| Arm | Count |
|---|---|
| 0.05 x 10^6 CAR+ T Cells/kg Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.05 x 10\^6 CAR+ T cells per kilogram (kg) post leukapheresis. | 9 |
| 0.15 x 10^6 CAR+ T Cells/kg Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.15 x 106 CAR+ T cells/kg post leukapheresis. | 8 |
| 0.50 x 106 CAR+T Cells/kg Participants with CD19+ relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) were infused with 0.50 x 106 CAR+T cells/kg post leukapheresis. | 3 |
| Not Assigned Participants only underwent leukapheresis. | 1 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Lymphodepleting Chemotherapy | Progressive Disease | 1 | 0 | 0 | 0 |
| Pre-Treatment Period | Death | 0 | 1 | 0 | 1 |
| Pre-Treatment Period | Failure to meet treatment criteria | 0 | 0 | 2 | 0 |
| Pre-Treatment Period | Study Drug Manufacturing Failure | 1 | 0 | 0 | 0 |
| Treatment Period (JCAR017 Infusion) | Death | 1 | 0 | 0 | 0 |
| Treatment Period (JCAR017 Infusion) | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Treatment Period (JCAR017 Infusion) | Other Reason | 1 | 0 | 0 | 0 |
| Treatment Period (JCAR017 Infusion) | Progressive Disease | 1 | 0 | 0 | 0 |
| Treatment Period (JCAR017 Infusion) | Study Terminated by Sponsor | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Not Assigned | 0.05 x 10^6 CAR+ T Cells/kg | 0.50 x 106 CAR+T Cells/kg | 0.15 x 10^6 CAR+ T Cells/kg |
|---|---|---|---|---|---|
| Age, Customized >= 12 to < 18 years | 3 participants | 1 participants | 1 participants | 0 participants | 1 participants |
| Age, Customized >= 6 to < 12 years | 9 participants | 0 participants | 5 participants | 1 participants | 3 participants |
| Age, Customized < 6 years | 9 participants | 0 participants | 3 participants | 2 participants | 4 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 1 Participants | 4 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 0 Participants | 4 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 14 Participants | 0 Participants | 6 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Female | 11 Participants | 0 Participants | 5 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 10 Participants | 1 Participants | 4 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 9 | 4 / 8 | 1 / 3 | 1 / 1 |
| other Total, other adverse events | 7 / 7 | 6 / 6 | 1 / 1 | 0 / 0 |
| serious Total, serious adverse events | 5 / 7 | 3 / 6 | 1 / 1 | 0 / 0 |
Outcome results
Primary
Concentration of JCAR017 in Peripheral Blood at Day 28 Post JCAR017 Infusion
Concentration of JCAR017 in Peripheral Blood was assessed by droplet digital polymerase chain reaction.
Time frame: At day 28 post JCAR017 infusion
Population: The PK Analysis Set include all participants who received JCAR017 infusion and have at least one measurable JCAR017 concentration. Participants available at specific timepoints have been analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.05 x 10^6 CAR+ T Cells/kg | Concentration of JCAR017 in Peripheral Blood at Day 28 Post JCAR017 Infusion | 1131.821 copies per microgram | Geometric Coefficient of Variation 64.658 |
| 0.15 x 10^6 CAR+ T Cells/kg | Concentration of JCAR017 in Peripheral Blood at Day 28 Post JCAR017 Infusion | 1457.591 copies per microgram | Geometric Coefficient of Variation 75.558 |
| 0.50 x 106 CAR+T Cells/kg | Concentration of JCAR017 in Peripheral Blood at Day 28 Post JCAR017 Infusion | 2847.910 copies per microgram | — |
Primary
Number of Participants With Dose Limiting Toxicities
A DLT was defined as: * Death not related to disease progression * Grade (Gr) 4 (Life-threatening) neurotoxicity * Gr 3 (Severe) neurotoxicity of greater than 7 days * Gr 3 neurotoxicity does not revert to baseline within 28 days of the start date of the Grade 3 event * Seizures of grade that do not resolve within 7 days * Gr 4 cytokine release syndrome (CRS) that does not resolve to Grade ≤ 3 within 3 days * Gr 3 CRS that does not resolve to Grade ≤ 2 within 7 days * Any increase in aspartate aminotransferase (AST) or ALT \> 3 × ULN and concurrent increase in total bilirubin \> 2 × ULN that is unrelated to CRS and has no other probable reason to explain the combination of increases * Any cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary, or neurologic Gr 3 or 4 event not pre-existing or not due to the underlying malignancy * Any other Gr 3 or 4 event deemed unexpected by the Investigator and considered a DLT upon evaluation by the safety review committee
Time frame: From first JCAR017 infusion (Day 1) to 28 days after JCAR017 infusion
Population: Dose-Limiting Toxicity Analysis Set included all participants who received conforming JCAR017 infusion and completed 28 days post JCAR017 infusion.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 0.05 x 10^6 CAR+ T Cells/kg | Number of Participants With Dose Limiting Toxicities | 0 Participants |
| 0.15 x 10^6 CAR+ T Cells/kg | Number of Participants With Dose Limiting Toxicities | 2 Participants |
| 0.50 x 106 CAR+T Cells/kg | Number of Participants With Dose Limiting Toxicities | 1 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events up to 30 Days Post JCAR017 Infusion
An AE is defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. Treatment Emergent Adverse Events (TEAEs) are defined as any AE occurring or worsening on the day of the JCAR017 infusion until 30 days post-treatment (JCAR017 infusion) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or greater.
Time frame: From first JCAR017 infusion (Day 1) to 30 days after JCAR017 infusion
Population: Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 0.05 x 10^6 CAR+ T Cells/kg | Number of Participants With Treatment Emergent Adverse Events up to 30 Days Post JCAR017 Infusion | 7 Participants |
| 0.15 x 10^6 CAR+ T Cells/kg | Number of Participants With Treatment Emergent Adverse Events up to 30 Days Post JCAR017 Infusion | 6 Participants |
| 0.50 x 106 CAR+T Cells/kg | Number of Participants With Treatment Emergent Adverse Events up to 30 Days Post JCAR017 Infusion | 1 Participants |
Secondary
Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Alanine Aminotransferase; Alkaline Phosphatase; Aspartate Aminotransferase; Lactate Dehydrogenase
Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.
Time frame: Baseline and at Day 28
Population: Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements. Participants available at specific timepoints have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Alanine Aminotransferase; Alkaline Phosphatase; Aspartate Aminotransferase; Lactate Dehydrogenase | Aspartate aminotransferase | 29.17 units per liter | Standard Deviation 72.204 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Alanine Aminotransferase; Alkaline Phosphatase; Aspartate Aminotransferase; Lactate Dehydrogenase | Alkaline phosphatase | 53.50 units per liter | Standard Deviation 158.322 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Alanine Aminotransferase; Alkaline Phosphatase; Aspartate Aminotransferase; Lactate Dehydrogenase | Lactate dehydrogenase | 992.33 units per liter | Standard Deviation 2238.888 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Alanine Aminotransferase; Alkaline Phosphatase; Aspartate Aminotransferase; Lactate Dehydrogenase | Alanine aminotransferase | 5.33 units per liter | Standard Deviation 19.439 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Alanine Aminotransferase; Alkaline Phosphatase; Aspartate Aminotransferase; Lactate Dehydrogenase | Aspartate aminotransferase | 11.50 units per liter | Standard Deviation 13.675 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Alanine Aminotransferase; Alkaline Phosphatase; Aspartate Aminotransferase; Lactate Dehydrogenase | Lactate dehydrogenase | 22.25 units per liter | Standard Deviation 43.684 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Alanine Aminotransferase; Alkaline Phosphatase; Aspartate Aminotransferase; Lactate Dehydrogenase | Alanine aminotransferase | 4.50 units per liter | Standard Deviation 16.299 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Alanine Aminotransferase; Alkaline Phosphatase; Aspartate Aminotransferase; Lactate Dehydrogenase | Alkaline phosphatase | 78.75 units per liter | Standard Deviation 40.95 |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Alanine Aminotransferase; Alkaline Phosphatase; Aspartate Aminotransferase; Lactate Dehydrogenase | Lactate dehydrogenase | -36.00 units per liter | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Alanine Aminotransferase; Alkaline Phosphatase; Aspartate Aminotransferase; Lactate Dehydrogenase | Aspartate aminotransferase | -1.00 units per liter | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Alanine Aminotransferase; Alkaline Phosphatase; Aspartate Aminotransferase; Lactate Dehydrogenase | Alkaline phosphatase | -121.00 units per liter | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Alanine Aminotransferase; Alkaline Phosphatase; Aspartate Aminotransferase; Lactate Dehydrogenase | Alanine aminotransferase | -19.00 units per liter | — |
Secondary
Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride
Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.
Time frame: Baseline and at Day 28
Population: Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements. Participants available at specific timepoints have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Triglyceride | 0.45 mmol/L | Standard Deviation 1.652 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Magnesium | 0.06 mmol/L | Standard Deviation 0.107 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Glucose | 0.32 mmol/L | Standard Deviation 0.641 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Sodium | 1.00 mmol/L | Standard Deviation 2.608 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Phosphate | 0.02 mmol/L | Standard Deviation 0.281 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Chloride | -1.50 mmol/L | Standard Deviation 4.324 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Potassium | -0.05 mmol/L | Standard Deviation 0.672 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Calcium | 0.13 mmol/L | Standard Deviation 0.157 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Bicarbonate | 2.53 mmol/L | Standard Deviation 4.453 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Blood Urea Nitrogen | 3.60 mmol/L | Standard Deviation 3.542 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Triglyceride | 0.29 mmol/L | Standard Deviation 0.32 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Blood Urea Nitrogen | 2.43 mmol/L | Standard Deviation 0.826 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Calcium | 0.04 mmol/L | Standard Deviation 0.058 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Chloride | 1.50 mmol/L | Standard Deviation 1.291 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Glucose | -0.08 mmol/L | Standard Deviation 0.472 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Magnesium | 0.06 mmol/L | Standard Deviation 0.109 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Phosphate | -0.02 mmol/L | Standard Deviation 0.336 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Potassium | 0.20 mmol/L | Standard Deviation 0.535 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Sodium | 2.25 mmol/L | Standard Deviation 2.217 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Bicarbonate | -2.65 mmol/L | Standard Deviation 1.919 |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Magnesium | 0.00 mmol/L | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Calcium | -0.17 mmol/L | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Sodium | 2.00 mmol/L | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Glucose | 14.90 mmol/L | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Triglyceride | 0.33 mmol/L | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Chloride | 1.00 mmol/L | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Blood Urea Nitrogen | 0.20 mmol/L | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Phosphate | -0.16 mmol/L | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Bicarbonate | 4.10 mmol/L | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bicarbonate; Blood Urea Nitrogen; Calcium; Chloride; Glucose; Magnesium; Phosphate; Potassium; Sodium, Triglyceride | Potassium | 1.50 mmol/L | — |
Secondary
Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bilirubin; Creatinine; Direct Bilirubin; Urate
Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.
Time frame: Baseline and at Day 28
Population: Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements. Participants available at specific timepoints have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bilirubin; Creatinine; Direct Bilirubin; Urate | Bilirubin | 20.26 umol/L | Standard Error 41.498 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bilirubin; Creatinine; Direct Bilirubin; Urate | Creatinine | 9.84 umol/L | Standard Error 14.218 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bilirubin; Creatinine; Direct Bilirubin; Urate | Direct Bilirubin | 13.44 umol/L | Standard Error 33.601 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bilirubin; Creatinine; Direct Bilirubin; Urate | Urate | 43.51 umol/L | Standard Error 94.081 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bilirubin; Creatinine; Direct Bilirubin; Urate | Urate | 85.00 umol/L | Standard Error 71.615 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bilirubin; Creatinine; Direct Bilirubin; Urate | Bilirubin | -1.00 umol/L | Standard Error 6.928 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bilirubin; Creatinine; Direct Bilirubin; Urate | Direct Bilirubin | -0.25 umol/L | Standard Error 0.5 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bilirubin; Creatinine; Direct Bilirubin; Urate | Creatinine | 1.50 umol/L | Standard Error 9 |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bilirubin; Creatinine; Direct Bilirubin; Urate | Urate | 9.00 umol/L | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bilirubin; Creatinine; Direct Bilirubin; Urate | Creatinine | -2.00 umol/L | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bilirubin; Creatinine; Direct Bilirubin; Urate | Direct Bilirubin | 0.00 umol/L | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Chemistry Laboratory Parameters- Bilirubin; Creatinine; Direct Bilirubin; Urate | Bilirubin | 2.00 umol/L | — |
Secondary
Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets
Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.
Time frame: Baseline and at Day 28
Population: Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements. Participants available at specific timepoints have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets | 27.33 10^9 cells/L | Standard Deviation 132.672 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Eosinophils | 0.03 10^9 cells/L | Standard Deviation 0.048 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Leukocytes | 4.01 10^9 cells/L | Standard Deviation 8.338 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes | 0.11 10^9 cells/L | Standard Deviation 0.163 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes | -0.22 10^9 cells/L | Standard Deviation 0.879 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils | 0.41 10^9 cells/L | Standard Deviation 0.782 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils | 0.00 10^9 cells/L | Standard Deviation 0.025 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Leukocytes | 0.59 10^9 cells/L | Standard Deviation 1.753 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes | 0.27 10^9 cells/L | Standard Deviation 1.286 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes | 0.09 10^9 cells/L | Standard Deviation 0.173 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets | -68.60 10^9 cells/L | Standard Deviation 168.583 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils | -0.01 10^9 cells/L | Standard Deviation 0.023 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Eosinophils | 0.08 10^9 cells/L | Standard Deviation 0.114 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils | -0.18 10^9 cells/L | Standard Deviation 0.735 |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets | -163.00 10^9 cells/L | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Eosinophils | -0.08 10^9 cells/L | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes | -0.57 10^9 cells/L | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils | -1.50 10^9 cells/L | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils | -0.01 10^9 cells/L | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes | -0.22 10^9 cells/L | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Leukocytes | -2.00 10^9 cells/L | — |
Secondary
Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils/Leukocytes; Eosinophils/Leukocytes; Lymphocytes/Leukocytes; Neutrophils/Leukocytes; Monocytes/Leukocytes
Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.
Time frame: Baseline and at Day 28
Population: Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements. Participants available at specific timepoints have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils/Leukocytes; Eosinophils/Leukocytes; Lymphocytes/Leukocytes; Neutrophils/Leukocytes; Monocytes/Leukocytes | Eosinophils/Leukocytes | 0.85 Ratio | Standard Deviation 1.402 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils/Leukocytes; Eosinophils/Leukocytes; Lymphocytes/Leukocytes; Neutrophils/Leukocytes; Monocytes/Leukocytes | Neutrophils/Leukocytes | 26.45 Ratio | Standard Deviation 26.815 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils/Leukocytes; Eosinophils/Leukocytes; Lymphocytes/Leukocytes; Neutrophils/Leukocytes; Monocytes/Leukocytes | Basophils/Leukocytes | 0.25 Ratio | Standard Deviation 0.885 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils/Leukocytes; Eosinophils/Leukocytes; Lymphocytes/Leukocytes; Neutrophils/Leukocytes; Monocytes/Leukocytes | Monocytes/Leukocytes | 4.35 Ratio | Standard Deviation 10.123 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils/Leukocytes; Eosinophils/Leukocytes; Lymphocytes/Leukocytes; Neutrophils/Leukocytes; Monocytes/Leukocytes | Lymphocytes/Leukocytes | -29.57 Ratio | Standard Deviation 21.69 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils/Leukocytes; Eosinophils/Leukocytes; Lymphocytes/Leukocytes; Neutrophils/Leukocytes; Monocytes/Leukocytes | Lymphocytes/Leukocytes | -16.30 Ratio | Standard Deviation 25.14 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils/Leukocytes; Eosinophils/Leukocytes; Lymphocytes/Leukocytes; Neutrophils/Leukocytes; Monocytes/Leukocytes | Eosinophils/Leukocytes | 4.28 Ratio | Standard Deviation 5.389 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils/Leukocytes; Eosinophils/Leukocytes; Lymphocytes/Leukocytes; Neutrophils/Leukocytes; Monocytes/Leukocytes | Neutrophils/Leukocytes | 10.70 Ratio | Standard Deviation 18.797 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils/Leukocytes; Eosinophils/Leukocytes; Lymphocytes/Leukocytes; Neutrophils/Leukocytes; Monocytes/Leukocytes | Monocytes/Leukocytes | 1.74 Ratio | Standard Deviation 4.515 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils/Leukocytes; Eosinophils/Leukocytes; Lymphocytes/Leukocytes; Neutrophils/Leukocytes; Monocytes/Leukocytes | Basophils/Leukocytes | -0.24 Ratio | Standard Deviation 0.654 |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils/Leukocytes; Eosinophils/Leukocytes; Lymphocytes/Leukocytes; Neutrophils/Leukocytes; Monocytes/Leukocytes | Monocytes/Leukocytes | 0.20 Ratio | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils/Leukocytes; Eosinophils/Leukocytes; Lymphocytes/Leukocytes; Neutrophils/Leukocytes; Monocytes/Leukocytes | Eosinophils/Leukocytes | -2.90 Ratio | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils/Leukocytes; Eosinophils/Leukocytes; Lymphocytes/Leukocytes; Neutrophils/Leukocytes; Monocytes/Leukocytes | Lymphocytes/Leukocytes | 33.80 Ratio | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils/Leukocytes; Eosinophils/Leukocytes; Lymphocytes/Leukocytes; Neutrophils/Leukocytes; Monocytes/Leukocytes | Neutrophils/Leukocytes | -33.90 Ratio | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils/Leukocytes; Eosinophils/Leukocytes; Lymphocytes/Leukocytes; Neutrophils/Leukocytes; Monocytes/Leukocytes | Basophils/Leukocytes | -0.30 Ratio | — |
Secondary
Change From Baseline at Day 28 in Hematology Laboratory Parameters- Erythrocytes
Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.
Time frame: Baseline and at Day 28
Population: Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements. Participants available at specific timepoints have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Erythrocytes | 0.04 10^12 cells/L | Standard Deviation 0.781 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Erythrocytes | 0.08 10^12 cells/L | Standard Deviation 0.268 |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Erythrocytes | -0.70 10^12 cells/L | — |
Secondary
Change From Baseline at Day 28 in Hematology Laboratory Parameters- Hematocrit
Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.
Time frame: Baseline and at Day 28
Population: Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements. Participants available at specific timepoints have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Hematocrit | 0.00 proportion of red blood cells in blood | Standard Deviation 0.068 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Hematocrit | 0.02 proportion of red blood cells in blood | Standard Deviation 0.016 |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Hematocrit | -0.03 proportion of red blood cells in blood | — |
Secondary
Change From Baseline at Day 28 in Hematology Laboratory Parameters- Hemoglobin
Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.
Time frame: Baseline and at Day 28
Population: Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements. Participants available at specific timepoints have been analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Hemoglobin | 2.33 grams per liter | Standard Deviation 24.312 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Hemoglobin | 6.20 grams per liter | Standard Deviation 6.834 |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Hematology Laboratory Parameters- Hemoglobin | -13.00 grams per liter | — |
Secondary
Change From Baseline at Day 28 in Laboratory Parameters- Albumin; Protein
Baseline is defined as the last assessment with non-missing value on or prior to the first date of the lymphodepletion chemotherapy.
Time frame: Baseline and at Day 28
Population: Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements. Participants available at specific timepoints have been analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Laboratory Parameters- Albumin; Protein | Albumin | 5.83 grams per liter | Standard Deviation 9.663 |
| 0.05 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Laboratory Parameters- Albumin; Protein | Protein | 4.00 grams per liter | Standard Deviation 12.602 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Laboratory Parameters- Albumin; Protein | Albumin | 6.75 grams per liter | Standard Deviation 2.062 |
| 0.15 x 10^6 CAR+ T Cells/kg | Change From Baseline at Day 28 in Laboratory Parameters- Albumin; Protein | Protein | 5.00 grams per liter | Standard Deviation 6.683 |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Laboratory Parameters- Albumin; Protein | Albumin | -3.00 grams per liter | — |
| 0.50 x 106 CAR+T Cells/kg | Change From Baseline at Day 28 in Laboratory Parameters- Albumin; Protein | Protein | -6.00 grams per liter | — |
Secondary
Duration of Response (DOR)
DOR is defined as time from first response (either CR or CRi) until progressive disease (PD), disease relapse, or death from any cause, whichever occurs first. Response assessment was performed according to the 2019 Comprehensive Cancer Network (NCCN) response criteria guidelines for pediatric ALL. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. CRi is defined as meeting all criteria for CR except platelets \< 100,000/μL or ANC is \< 1000/μL. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease.
Time frame: From first response (either CR or CRi) until progressive disease (PD), disease relapse, or death from any cause, whichever occurs first (Up to approximately 14 months)
Population: Efficacy Analysis Set included all participants who fulfilled all study eligibility criteria, received conforming JCAR017 infusion, who did not demonstrate morphological remission at screening and who are not MRD negative upon restaging prior to initiation of lymphodepleting (LD) chemotherapy. Responders (either CR or CRi) are included in the analysis. Censored participants were also analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.05 x 10^6 CAR+ T Cells/kg | Duration of Response (DOR) | 13.70 months |
| 0.15 x 10^6 CAR+ T Cells/kg | Duration of Response (DOR) | NA months |
| 0.50 x 106 CAR+T Cells/kg | Duration of Response (DOR) | NA months |
Secondary
Event Free Survival (EFS)
EFS is defined as time from conforming JCAR017 infusion to progressive disease (PD), relapsed disease, start of a new anticancer therapy including HSCT or death from any cause, whichever occurs first. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease. Relapsed disease is defined as Reappearance of blasts in the blood or bone marrow (\> 5%) or \> 1% with previous/supportive molecular findings or in any extramedullary site after a CR. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. Only responders are included in he analysis. Censored participants were also analyzed.
Time frame: From conforming JCAR017 infusion to PD, relapsed disease, start of a new anticancer therapy including Hematopoietic Stem Cell Transplant (HSCT) or death from any cause, whichever occurs first (Up to approximately 15 months)
Population: Efficacy Analysis Set included all participants who fulfilled all study eligibility criteria, received conforming JCAR017 infusion, who did not demonstrate morphological remission at screening and who are not MRD negative upon restaging prior to initiation of lymphodepleting (LD) chemotherapy. Disease assessments reported after a PD or relapsed disease were not considered for the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.05 x 10^6 CAR+ T Cells/kg | Event Free Survival (EFS) | 3.24 months |
| 0.15 x 10^6 CAR+ T Cells/kg | Event Free Survival (EFS) | 5.42 months |
| 0.50 x 106 CAR+T Cells/kg | Event Free Survival (EFS) | 3.12 months |
Secondary
Minimal Residual Response (MRD) Negative Response Rate
Minimal Residual Disease (MRD) Negative Response Rate is defined as the percentage of participants achieving either a CR or CRi with a MRD negative bone marrow on Day 28, confirmed on Day 56. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. CRi is defined as meeting all criteria for CR except platelets \< 100,000/μL or ANC is \< 1000/μL. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease. Disease assessments recorded on or after start of a new anticancer therapy, including HSCT, will not be considered, nor will disease assessments reported after a PD or relapse has been observed.
Time frame: Up to Day 56
Population: Efficacy Analysis Set included all participants who fulfilled all study eligibility criteria, received conforming JCAR017 infusion, who did not demonstrate morphological remission at screening and who are not MRD negative upon restaging prior to initiation of lymphodepleting (LD) chemotherapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.05 x 10^6 CAR+ T Cells/kg | Minimal Residual Response (MRD) Negative Response Rate | 16.7 percentage of participants |
| 0.15 x 10^6 CAR+ T Cells/kg | Minimal Residual Response (MRD) Negative Response Rate | 25.0 percentage of participants |
| 0.50 x 106 CAR+T Cells/kg | Minimal Residual Response (MRD) Negative Response Rate | 100.0 percentage of participants |
Secondary
Number of Participants Who Achieved a Response After JCAR017 Infusion and Then Proceeded to Hematopoietic Stem Cell Transplant
Number of participants who undergo HSCT after receiving a JCAR017 infusion and achieving a response are presented. The time of proceeding to HSCT is defined as the time of commencing the conditioning regimen as required for HSCT. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. CRi is defined as meeting all criteria for CR except platelets \< 100,000/μL or ANC is \< 1000/μL. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease.
Time frame: Up to approximately 24 months
Population: Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 0.05 x 10^6 CAR+ T Cells/kg | Number of Participants Who Achieved a Response After JCAR017 Infusion and Then Proceeded to Hematopoietic Stem Cell Transplant | 1 Participants |
| 0.15 x 10^6 CAR+ T Cells/kg | Number of Participants Who Achieved a Response After JCAR017 Infusion and Then Proceeded to Hematopoietic Stem Cell Transplant | 1 Participants |
| 0.50 x 106 CAR+T Cells/kg | Number of Participants Who Achieved a Response After JCAR017 Infusion and Then Proceeded to Hematopoietic Stem Cell Transplant | 1 Participants |
Secondary
Number of Participants With Manufacturing Success of JCAR017 Product
Successful product was defined as JCAR017 product was generated and able to be QC released (including nonconforming product) for infusion. Unsuccessful product is defined as no JCAR017 product could be generated after two manufacturing attempts using a single apheresis product for starting material or product was unable to be QC released for infusion.
Time frame: From screening to JCAR017 infusion (day -35 to day 1)
Population: Pre-Treatment Set included all participants who have screened successfully into the study and underwent leukapheresis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 0.05 x 10^6 CAR+ T Cells/kg | Number of Participants With Manufacturing Success of JCAR017 Product | 7 Participants |
| 0.15 x 10^6 CAR+ T Cells/kg | Number of Participants With Manufacturing Success of JCAR017 Product | 7 Participants |
| 0.50 x 106 CAR+T Cells/kg | Number of Participants With Manufacturing Success of JCAR017 Product | 2 Participants |
| Not Assigned | Number of Participants With Manufacturing Success of JCAR017 Product | 1 Participants |
Secondary
Number of Participants With Serious Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion
Serious adverse events (SAE) are defined as any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/ birth defect; constitutes an important medical event. Treatment Emergent Adverse Events (TEAEs) are defined as any AE occurring or worsening on the day of the JCAR017 infusion until 90 days post-treatment (JCAR017 infusion) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or greater.
Time frame: From first JCAR017 infusion (Day 1) to 90 days after JCAR017 infusion
Population: Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 0.05 x 10^6 CAR+ T Cells/kg | Number of Participants With Serious Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion | AT Least one Serious TEAE | 5 Participants |
| 0.05 x 10^6 CAR+ T Cells/kg | Number of Participants With Serious Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion | At Least One Serious TEAE Related To JCAR017 | 1 Participants |
| 0.15 x 10^6 CAR+ T Cells/kg | Number of Participants With Serious Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion | AT Least one Serious TEAE | 3 Participants |
| 0.15 x 10^6 CAR+ T Cells/kg | Number of Participants With Serious Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion | At Least One Serious TEAE Related To JCAR017 | 3 Participants |
| 0.50 x 106 CAR+T Cells/kg | Number of Participants With Serious Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion | AT Least one Serious TEAE | 1 Participants |
| 0.50 x 106 CAR+T Cells/kg | Number of Participants With Serious Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion | At Least One Serious TEAE Related To JCAR017 | 1 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion
An AE is defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. Treatment Emergent Adverse Events (TEAEs) are defined as any AE occurring or worsening on the day of the JCAR017 infusion until 90 days post-treatment (JCAR017 infusion) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or greater. The following scale for grading was used - Grade 3 = Severe, Grade 4 = Life-Threatening.
Time frame: From first JCAR017 infusion (Day 1) to 90 days after JCAR017 infusion
Population: Safety Analysis Set included all participants who received conforming JCAR017 infusion with baseline and post-baseline measurements.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 0.05 x 10^6 CAR+ T Cells/kg | Number of Participants With Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion | At least one TEAE | 7 Participants |
| 0.05 x 10^6 CAR+ T Cells/kg | Number of Participants With Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion | At Least One TEAE Related To JCAR017 | 5 Participants |
| 0.05 x 10^6 CAR+ T Cells/kg | Number of Participants With Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion | At least one grade 3/4 TEAE | 6 Participants |
| 0.05 x 10^6 CAR+ T Cells/kg | Number of Participants With Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion | At Least One grade 3/4 TEAE Related To JCAR017 | 3 Participants |
| 0.15 x 10^6 CAR+ T Cells/kg | Number of Participants With Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion | At Least One grade 3/4 TEAE Related To JCAR017 | 4 Participants |
| 0.15 x 10^6 CAR+ T Cells/kg | Number of Participants With Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion | At Least One TEAE Related To JCAR017 | 5 Participants |
| 0.15 x 10^6 CAR+ T Cells/kg | Number of Participants With Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion | At least one TEAE | 6 Participants |
| 0.15 x 10^6 CAR+ T Cells/kg | Number of Participants With Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion | At least one grade 3/4 TEAE | 5 Participants |
| 0.50 x 106 CAR+T Cells/kg | Number of Participants With Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion | At Least One TEAE Related To JCAR017 | 1 Participants |
| 0.50 x 106 CAR+T Cells/kg | Number of Participants With Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion | At least one grade 3/4 TEAE | 1 Participants |
| 0.50 x 106 CAR+T Cells/kg | Number of Participants With Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion | At Least One grade 3/4 TEAE Related To JCAR017 | 1 Participants |
| 0.50 x 106 CAR+T Cells/kg | Number of Participants With Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion | At least one TEAE | 1 Participants |
Secondary
Overall Response Rate (ORR)
ORR is defined as the percentage of participants who achieved either a complete response (CR) or complete response with incomplete blood recovery (CRi) on Day 28 that is confirmed on Day 56. Response assessment was performed according to the 2019 Comprehensive Cancer Network (NCCN) response criteria guidelines for pediatric acute lymphoblastic leukemia (ALL). CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks. CRi is defined as meeting all criteria for CR except platelets \< 100,000/μL or ANC is \< 1000/μL.
Time frame: Up to Day 56
Population: Efficacy Analysis Set included all participants who fulfilled all study eligibility criteria, received conforming JCAR017 infusion, who did not demonstrate morphological remission at screening and who are not MRD negative upon restaging prior to initiation of lymphodepleting (LD) chemotherapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.05 x 10^6 CAR+ T Cells/kg | Overall Response Rate (ORR) | 50.0 percentage of participants |
| 0.15 x 10^6 CAR+ T Cells/kg | Overall Response Rate (ORR) | 25.0 percentage of participants |
| 0.50 x 106 CAR+T Cells/kg | Overall Response Rate (ORR) | 100.0 percentage of participants |
Secondary
Overall Survival (OS)
OS is defined as the interval from the date of first confirming JCAR017 infusion to the date of death due to any reason.
Time frame: From the date of first confirming JCAR017 infusion to the date of death due to any reason (Up to approximately 24 months)
Population: Efficacy Analysis Set included all participants who fulfilled all study eligibility criteria, received conforming JCAR017 infusion, who did not demonstrate morphological remission at screening and who are not MRD negative upon restaging prior to initiation of lymphodepleting (LD) chemotherapy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.05 x 10^6 CAR+ T Cells/kg | Overall Survival (OS) | 7.13 months |
| 0.15 x 10^6 CAR+ T Cells/kg | Overall Survival (OS) | 7.08 months |
| 0.50 x 106 CAR+T Cells/kg | Overall Survival (OS) | 8.90 months |
Secondary
Relapse Free Survival (RFS)
RFS is defined as time from conforming JCAR017 infusion to the first progressive disease (PD), relapsed disease or death from any cause, whichever occurs first. Disease progression is defined as increase of at least 25% in the absolute number of circulating or bone marrow blasts or development of extramedullary disease. Relapsed disease is defined as Reappearance of blasts in the blood or bone marrow (\> 5%) or \> 1% with previous/supportive molecular findings or in any extramedullary site after a CR. CR is defined as absence of circulating blasts, extramedullary disease, lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement, Trilineage hematopoiesis (TLH) and \< 5%, Absolute neutrophil count (ANC) \> 1000 per microliter, Platelets \> 100,000 per microliter and no recurrence for 4 weeks.
Time frame: Up to approximately 15 months
Population: Efficacy Analysis Set included all participants who fulfilled all study eligibility criteria, received conforming JCAR017 infusion, who did not demonstrate morphological remission at screening and who are not MRD negative upon restaging prior to initiation of lymphodepleting (LD) chemotherapy. Only responders are included in he analysis. Censored participants were also analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 0.05 x 10^6 CAR+ T Cells/kg | Relapse Free Survival (RFS) | 7.77 months |
| 0.15 x 10^6 CAR+ T Cells/kg | Relapse Free Survival (RFS) | 6.98 months |
| 0.50 x 106 CAR+T Cells/kg | Relapse Free Survival (RFS) | NA months |