A Study Evaluating the Safety and Efficacy of Brexucabtagene Autoleucel (KTE-X19) in Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ZUMA-3)

Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia Clinical Trial

— ZUMA-3  

Official title:

A Phase 1/2 Multi-Center Study Evaluating the Safety and Efficacy of KTE-X19 in Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r ALL) (ZUMA-3)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02614066
• Other study ID #: KTE-C19-103
• Secondary ID: 2015-005009-35
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 7, 2016
• Est. completion date: November 3, 2023

Study information

• Verified date: November 2023
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objectives of this study are to determine the safety and efficacy of brexucabtagene autoleucel (KTE-X19) in adult participants with relapsed/refractory (r/r) B-precursor acute lymphoblastic leukemia (ALL).

Description:

Bridging therapy could be administered at the discretion of the investigator and is recommended for participants with high disease burden at baseline (M3 marrow [> 25% leukemic blasts] or ≥ 1,000 blasts/mm^3 in the peripheral circulation) to control participant's disease prior to conditioning chemotherapy. Bridging therapy includes: Attenuated VAD: Vincristine non-liposomal (1-2 mg IV weekly) or liposomal (2.25 mg/m^2 IV weekly), and dexamethasone 20-40 mg IV or oral administration (PO) daily x 3-4 days per week. Optional doxorubicin 50 mg/m^2 IV x 1 (first week only). Mercaptopurine (6-MP): 50-75 mg/m^2/day by mouth (administer at bedtime on an empty stomach to improve absorption). Hydroxyurea: Doses titrated between 15-50 mg/kg/day (rounded to the nearest 500 mg capsule and given as a single daily oral dose on a continuous basis). DOMP: Dexamethasone 6 mg/m^2/day PO (or IV) divided twice daily (BID) Days 1-5, vincristine 1.5 mg/m^2 (maximum dose 2 mg) IV on Day 1, methotrexate 20 mg/m^2 PO weekly, 6-MP 50- 75mg/m^2/day PO daily. Attenuated FLAG/FLAG-IDA: fludarabine 30 mg/m^2 IV days 1-2, cytarabine 2 g/m^2 IV days 1-2, G-CSF 5 μg/kg subcutaneously (SC) or IV starts on Day 3 and can continue until day before the start of conditioning chemotherapy. With or without idarubicin 6 mg/m^2 IV Days 1-2. Mini-hyper CVAD (courses A and/or B): Course A: Cyclophosphamide 150 mg/m^2 every 12 hours x 3 days, dexamethasone 20 mg/d IV or PO daily Days 1-4 and 11-14, vincristine 2 mg IV x 1 Course B: methotrexate 250 mg/m^2 IV over 24 hours on Day 1,cytarabine 0.5 g/m^2 IV every 12 hours x 4 doses on Days 2 and 3. After completion of the Month 24 visit, subjects who received an infusion of KTE-X19 will complete the remainder of the 15 year follow-up assessments in a separate long-term follow-up study, KT-US-982-5968

Recruitment information / eligibility

• Status: Completed
• Enrollment: 125
• Est. completion date: November 3, 2023
• Est. primary completion date: September 9, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

1. Relapsed or refractory B-precursor ALL defined as one of the following:

• Primary refractory disease
• First relapse if first remission = 12 months
• Relapsed or refractory disease after 2 or more lines of systemic therapy
• Relapsed or refractory disease after allogeneic transplant provided individuals is at least 100 days from stem cell transplant at the time of enrollment

2. Morphological disease in the bone marrow (= 5% blasts)

3. Individuals with Philadelphia chromosome positive (Ph+) disease are eligible if they are intolerant to tyrosine kinase inhibitor (TKI) therapy, or if they have relapsed/refractory disease despite treatment with at least 2 different TKIs

4. Eastern cooperative oncology group (ECOG) performance status of 0 or 1

5. Adequate renal, hepatic, pulmonary and cardiac function defined as:

• Creatinine clearance (as estimated by Cockcroft Gault) = 60 cc/min
• Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) = 2.5 x upper limit of normal (ULN)
• Total bilirubin = 1.5 mg/dl, except in individuals with Gilbert's syndrome.
• Cardiac ejection fraction = 50%, no evidence of pericardial effusion, and no clinically significant arrhythmias
• Baseline oxygen saturation > 92% on room air

6. In individuals previously treated with blinatumomab, cluster of differentiation 19 (CD19) tumor expression in bone marrow or peripheral blood.

Key Exclusion Criteria:

1. Diagnosis of Burkitt's leukemia/lymphoma according to World Health Organization (WHO) classification or chronic myelogenous leukemia lymphoid blast crisis

2. History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 3 years

3. Isolated extramedullary disease

4. Central nervous system (CNS) abnormalities

• Presence of CNS-3 disease or CNS-2 disease with neurological changes
• History or presence of any CNS disorder such as a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement

5. History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome or any other known bone marrow failure syndrome

6. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment

7. History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment.

8. Primary immunodeficiency

9. Known infection with human immunodeficiency virus (HIV), hepatitis B (HBsAg positive) or hepatitis C virus.

10. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management.

11. Prior medication:

• Salvage chemotherapy including TKIs for Ph+ ALL within 1 week prior to enrollment
• Prior CD19 directed therapy other than blinatumomab
• Treatment with alemtuzumab within 6 months prior to leukapheresis, or treatment with clofarabine or cladribine within 3 months prior to leukapheresis
• Donor lymphocyte infusion (DLI) within 28 days prior to enrollment
• Any drug used for graft-versus-host disease (GVHD) within 4 weeks prior to enrollment
• At least 3 half-lives must have elapsed from any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy prior to enrollment
• Corticosteroid therapy for 7 days prior to enrollment

12. Presence of any indwelling line or drain (e.g., percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Ommaya reservoirs and dedicated central venous access catheters such as a Port-a-Cath or Hickman catheter are permitted

13. Acute GVHD grade II-IV by Glucksberg criteria or severity B-D by IBMTR index; acute or chronic GVHD requiring systemic treatment within 4 weeks prior to enrollment

14. Live vaccine = 4 weeks prior to enrollment

15. 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. Females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential

16. Individuals of both genders of child-bearing potential who are not willing to practice birth control from the time of consent through 6 months after the completion of brexucabtagene autoleucel (KTE-X19)

17. In the investigators judgment, the individuals is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation

18. History of autoimmune disease (e.g. Crohns, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia

Intervention

Biological:
• brexucabtagene autoleucel
A single infusion of brexucabtagene autoleucel CAR transduced autologous T cells administered intravenously.

Drug:
• Cyclophosphamide
Administered intravenously.
• Fludarabine
Administered intravenously.

Locations

Country	Name	City	State
Canada	University Health Network - Princess Margaret	Toronto	Ontario
France	Institut Paoli Calmettes	Marseille
France	Hopital Saint Louis	Paris
France	Hopital Haut-Leveque	Pessac
France	Hopital Pontchaillou - CHU de Rennes - Service d'Hematologie	Rennes
Germany	Universitatsklinikum Frankfurt	Frankfurt
Germany	Klinikum der Universitat Munchen	München
Germany	Universitaetsklinikum Wuerzburg	Würzburg
Netherlands	Amsterdam UMC	Amsterdam
Netherlands	Erasmus MC	Rotterdam
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
United States	Emory University	Atlanta	Georgia
United States	University of MD Greenbaum Comprehensive Cancer Center	Baltimore	Maryland
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Loyola University	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	UC San Diego-Moores Cancer Center	La Jolla	California
United States	University of California Los Angeles (UCLA)	Los Angeles	California
United States	Sarah Cannon	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai Tisch Cancer Institute	New York	New York
United States	University of Rochester	New York	New York
United States	University of California Irvine Medical Center	Orange	California
United States	Mayo Clinic	Rochester	Minnesota
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of California San Francisco	San Francisco	California
United States	Seattle Cancer Center	Seattle	Washington
United States	Swedish Cancer Institute	Seattle	Washington
United States	H Lee Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Kite, A Gilead Company

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Netherlands, 

References & Publications (17)

Oluwole OO, Shah BD, Baer MR, Bishop MR, Holmes H, Schiller GJ, et al. Outcomes of Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia Treated with Prior Blinatumomab in ZUMA-3, a Study of KTE-C19, an Anti-CD19 Chimeric Antigen Receptor (CAR) T

Sabatino M, Choi K, Chiruvolu V, Better M. Production of Anti-CD19 CAR T Cells for ZUMA-3 and -4: Phase 1/2 Multicenter Studies Evaluating KTE-C19 in Patients With Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia (R/R ALL) [Abstract 711]. Bloo

Shah B, Castro J, Gokbuget N, Kersten MJ, Hagenbeek T, Wierda W, et al. ZUMA-3: A Phase 1/2 Multi-center Study Evaluating the Safety and Efficacy of KTE-C19 Anti-CD19 CAR T Cells in Adult Subjects with Relapsed/Refractory B Precursor Acute Lymphoblastic L

Shah B, Huynh V, Sender LS, Lee DW, Castro JE, Wierda WG, et al. High Rates of Minimal Residual Disease-Negative (MRD-) Complete Responses (CR) in Adult and Pediatric and Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia (R/R ALL) Treated Wit

Shah B, Stock W, Wierda W, Topp M, Kersten MJ, Houot R, et al. KTE-C19, an Anti-CD19 Chimeric Antigen Receptor (CAR) T cell Therapy in Adult Patients (Pts) With Relapsed/ Refractory Acute Lymphoblastic Leukemia (R/R ALL) in the ZUMA-3 Trial: Preliminary R

Shah B, Stock W, Wierda W, Topp MS, Kersten MJ, Houot R, et al. Preliminary Results of Novel Safety Interventions in Adult Patients (Pts) With Relapsed/Refractory Acute Lymphoblastic Leukemia (R/R ALL) in the ZUMA-3 Trial. European Society for Medical Onc

Shah B, Wierda WG, Schiller GJ, Bishop MR, Castro JE, Sabatino M, et al. KTE-C19 Chimeric Antigen Receptor (CAR) T Cell Therapy in Adults with High-Burden Relapsed/Refractory Acute Lymphoblastic Leukemia (R/R ALL): Updated Results from Phase 1/2 of ZUMA-3

Shah BD, Bishop MR, Oluwole OO, Logan A, Baer MR, Donnellan WB, et al. End of Phase I Results of ZUMA-3, A Phase 1/2 Study of KTE-X19, Anti-CD19 Chimeric Antigen Receptor (CAR) T Cell Therapy, in Adult Patients (pts) with Relapsed/Refractory (R/R) Acute L

Shah BD, Bishop MR, Oluwole OO, Logan AC, Baer MR, Donnellan WB, et al. KTE-X19, an Anti-CD19 Chimeric Antigen Receptor T Cell Therapy, in Adult Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia: End of Phase 1 Results of ZUMA-3 [Abstract PS9

Shah BD, Bishop MR, Oluwole OO, Logan AC, Baer MR, Donnellan WB, O'Dwyer KM, Holmes H, Arellano ML, Ghobadi A, Pagel JM, Lin Y, Cassaday RD, Park JH, Abedi M, Castro JE, DeAngelo DJ, Malone AK, Mawad R, Schiller GJ, Rossi JM, Bot A, Shen T, Goyal L, Jain — View Citation

Shah BD, Ghobadi A, Oluwole OO, Logan AC, Boissel N, Cassaday RD, Leguay T, Bishop MR, Topp MS, Tzachanis D, O'Dwyer KM, Arellano ML, Lin Y, Baer MR, Schiller GJ, Park JH, Subklewe M, Abedi M, Minnema MC, Wierda WG, DeAngelo DJ, Stiff P, Jeyakumar D, Feng — View Citation

Shah BD, Oluwole OO, Baer MR, Bishop MR, Holmes H, Schiller GJ, et al. KTE-C19, an Anti-CD19 Chimeric Antigen Receptor (CAR) T Cell Therapy, in Adult Patients with Relapsed/ Refractory Acute Lymphoblastic Leukemia (R/R ALL): Outcomes in Patients Who Were

Shah BD, Oluwole OO, Baer MR, Bishop MR, Holmes H, Schiller GJ, et al. Outcomes of Patients Treated With Prior Blinatumomab in ZUMA-3, a Study of KTE-C19, an Anti-CD19 Chimeric Antigen Receptor T Cell Therapy, in Adult Patients With Relapsed/Refractory Ac

Shah BD, Stock W, Wierda WG, Oluwole O, Holmes H, Schiller GJ, et al. Phase 1 Results of ZUMA-3: KTE-C19, an Anti-CD19 Chimeric Antigen Receptor (CAR) T Cell Therapy, in Adult Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia (R/R ALL) [Abstr

Shah BD, Wierda WG, Schiller GJ, Bishop MR, Castro JE, Sabatino M, et al. Updated results from ZUMA- 3, a phase 1/2 study of KTE-C19 chimeric antigen receptor (CAR) T cell therapy, in adults with high-burden relapsed/refractory acute lymphoblastic leukemi

Wierda WG, Bishop MR, Oluwole O, Logan AC, Baer MR, Donnellan WB, et al. Updated Phase 1 Results of Zuma-3: Kte-X19, an Anti-CD19 Chimeric Antigen Receptor T Cell Therapy, in Adult Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia [Abstract 2

Wierda WG, Bishop MR, Oluwole OO, Logan AC, Baer MR, Donnellan WB, et al. Updated Phase 1 Results of Zuma-3: Kte-C19, an Anti-CD19 Chimeric Antigen Receptor T Cell Therapy, in Adult Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia [Abstract]

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)	DLT is drug-related events with onset within first 28 days following infusion: Grade (GR) 4 hematologic toxicity lasting more than 30 days (except lymphopenia) if not attributable to underlying disease; All drug-related GR 3 lasting for > 7 days or 4 non-hematologic toxicities regardless of duration (except: aphasia/dysphasia or confusion/cognitive disturbance which resolves to at least GR 1/baseline within 2 weeks or baseline within 4 weeks, fever GR 3/ 4, immediate hypersensitivity reactions within 2 hours of drug infusion that are reversible = GR 2 within 24 hours, renal toxicity which requires dialysis for = 7 days, intubation for airway protection if = 7 days, tumor lysis syndrome, GR 3 liver function test elevation, provided there is resolution to = GR 2 within 14 days, GR 4 transient serum hepatic enzyme abnormalities provided there is resolution to = GR 3 within < 72 hours, hypogammaglobulinemia GR 3/ 4 and GR 3 nausea and/or anorexia).	First infusion date of brexucabtagene autoleucel up to 28 days. Participants were evaluated in specified period but GR4 hematologic toxicity (specified in description) having onset in this period were further observed for 30 days for confirmation
Primary	Phase 2: Overall Complete Remission (OCR) Rate (Complete Remission [CR]+ Complete Remission With Incomplete Hematologic Recovery [CRi]) as Assessed Per Independent Review	OCR rate: percentage of participants achieving CR+CRi. CR: =5% blasts by morphology in bone marrow (BM); absolute neutrophil count (ANC) =1000 and platelets (Plt) =100000 in peripheral blood (PB); central nervous system extramedullary disease (CNS EMD) of CNS-1 (no detectable leukemia in cerebrospinal fluid [CSF]); Non-CNS EMD: if baseline EMD present (images must show CR), if no baseline EMD (then images not required), but if performed should show negative positron emission tomography (PET) baseline, baseline lesions must show CR as disappearance of measurable and nonmeasurable nodal lesions (Nodal masses >1.5 cm in greatest transverse diameter [GTD] at baseline must have regressed to =l.5 cm GTD, nodes that were 1.1 to 1.5 cm [long axis] and >1.0 cm [short axis] must have decreased to 1.0 cm in their short axis, spleen and/or liver must be normal size, if tested) and no new lesions. CRi: all CR criteria except in PB ANC =1000 and Plt <100000 or ANC <1000 and Plt =100000.	First infusion date of brexucabtagene autoleucel (Phase 2) to data cutoff date of 09 September 2020 (Maximum duration: 23 Months)
Secondary	Phase 2: Minimum Residual Disease (MRD) Negative Remission Rate	MRD was assessed utilizing multicolor flow cytometry to detect residual cancerous cells with a sensitivity of 10^-4. MRD negative remission was defined as MRD < 10^-4 threshold. Percentage of participants with MRD negative remission was reported.	First infusion date of brexucabtagene autoleucel (Phase 2) to data cutoff date of 09 September 2020 (Maximum duration: 23 Months)
Secondary	Phase 2: Complete Remission (CR) Rate Per Independent Review	CR: = 5% blasts by morphology in BM; ANC = 1000 and Plt = 100000 in PB; CNS EMD of CNS-1 (no detectable leukemia in CSF); Non-CNS EMD: if baseline EMD present (images must show CR), if no baseline EMD (then images not required), but if performed should show negative PET baseline, baseline lesions must show CR as disappearance of measurable and nonmeasurable nodal lesions (Nodal masses > 1.5 cm in GTD at baseline must have regressed to = l.5 cm GTD, nodes that were 1.1 to 1.5 cm [long axis] and > 1.0 cm [short axis] must have decreased to 1.0 cm in their short axis, spleen and/or liver must be normal size, if tested) and no new lesions. Percentage of participants with CR was reported.	First infusion date of brexucabtagene autoleucel (Phase 2) to data cutoff date of 09 September 2020 (Maximum duration: 23 Months)
Secondary	Phase 2: Complete Remission With Incomplete Hematologic Recovery (CRi) Rate Per Independent Review	CRi: = 5% blasts by morphology in BM; ANC = 1000 and Plt < 100000 or ANC < 1000 and Plt = 100000 in PB; CNS EMD of CNS-1 (no detectable leukemia in CSF); Non-CNS EMD: if baseline EMD present (images must show CR), if no baseline EMD (then images not required), but if performed should show negative PET baseline, baseline lesions must show CR as disappearance of measurable and nonmeasurable nodal lesions (Nodal masses > 1.5 cm in GTD at baseline must have regressed to = l.5 cm GTD, nodes that were 1.1 to 1.5 cm [long axis] and > 1.0 cm [short axis] must have decreased to 1.0 cm in their short axis, spleen and/or liver must be normal size, if tested) and no new lesions. Percentage of participants with CRi was reported.	First infusion date of brexucabtagene autoleucel (Phase 2) to data cutoff date of 09 September 2020 (Maximum duration: 23 Months)
Secondary	Phase 2: Duration of Remission (DOR) Per Independent Review	DOR was defined as the time from first CR or CRi to relapse or any death in the absence of documented relapse. CR and CRi are defined in Outcome Measures 4 and 5. Relapse: = 5% blasts by morphology in BM; or circulating leukemia present in PB; or CNS EMD of CNS-2 (detectable CSF blast cells in a sample of CSF with < 5 white blood cells [WBCs] per mm^3 with neurological changes) or CNS-3 (detectable CSF blast cells in a sample of CSF with = 5 WBCs per mm^3 with or without neurological changes); or progressive disease (PD): at least one of the following (= 50% increase from nadir in the sum of the products of at least two lymph nodes, or if a single node is involved at least a 50% increase in the product of the diameters of this one node; at least a 50% increase in the longest diameter of any single previously identified node more than 1 cm in its short axis; = 50% increase in size of splenic, hepatic or any other non-nodal lesion). Kaplan-Meier (KM) estimates was used for analyses.	From first CR or CRi (Phase 2) to relapse/death or data cutoff date of 09 September 2020 (Maximum duration: 23 Months)
Secondary	Phase 2: OCR Rate (CR + CRi) Per Investigator Review	OCR rate: percentage of participants achieving CR+CRi. CR: = 5% blasts by morphology in BM; ANC =1000 and Plt = 100000 in PB; CNS EMD of CNS-1 (no detectable leukemia in CSF); Non-CNS EMD: if baseline EMD present (images must show CR), if no baseline EMD (then images not required), but if performed should show negative PET baseline, baseline lesions must show CR as disappearance of measurable and nonmeasurable nodal lesions (Nodal masses >1.5 cm in GTD at baseline must have regressed to =l.5 cm GTD, nodes that were 1.1 to 1.5 cm [long axis] and >1.0 cm [short axis] must have decreased to 1.0 cm in their short axis, spleen and/or liver must be normal size, if tested) and no new lesions. CRi: all CR criteria except in PB ANC =1000 and Plt <100000 or ANC <1000 and Plt =100000.	First infusion date of brexucabtagene autoleucel (Phase 2) to data cutoff date of 09 September 2020 (Maximum duration: 23 Months)
Secondary	Phase 2: Percentage of Participants With Allogeneic Stem Cell Transplant (Allo-SCT)		First infusion date of brexucabtagene autoleucel (Phase 2) to data cutoff date of 09 September 2020 (Maximum duration: 23 Months)
Secondary	Phase 2: MRD Negative Rate Among Complete Remission (CR) Participants	Percentage of participants with MRD negative remission among CR participants was reported. MRD was assessed utilizing multicolor flow cytometry to detect residual cancerous cells with a sensitivity of 10^-4. MRD negative remission was defined as MRD < 10^-4 threshold. CR: =5% blasts by morphology in BM; ANC = 1000 and Plt = 100000 in PB; CNS EMD of CNS-1 (no detectable leukemia in CSF); Non-CNS EMD: if baseline EMD present (images must show CR), if no baseline EMD (then images not required), but if performed should show negative PET baseline, baseline lesions must show CR as disappearance of measurable and nonmeasurable nodal lesions (Nodal masses > 1.5 cm in GTD at baseline must have regressed to = l.5 cm GTD, nodes that were 1.1 to 1.5 cm [long axis] and > 1.0 cm [short axis] must have decreased to 1.0 cm in their short axis, spleen and/or liver must be normal size, if tested) and no new lesions.	First infusion date of brexucabtagene autoleucel (Phase 2) to data cutoff date of 09 September 2020 (Maximum duration: 23 Months)
Secondary	Phase 2: MRD Negative Rate Among Complete Remission With Incomplete Hematologic Recovery (CRi) Participants	Percentage of participants with MRD negative remission among CRi participants was reported. MRD was assessed utilizing multicolor flow cytometry to detect residual cancerous cells with a sensitivity of 10^-4. MRD negative remission was defined as MRD < 10^-4 threshold. CRi: = 5% blasts by morphology in BM; ANC = 1000 and Plt < 100000 or ANC < 1000 and Plt = 100000 in PB; CNS EMD of CNS-1 (no detectable leukemia in CSF); Non-CNS EMD: if baseline EMD present (images must show CR), if no baseline EMD (then images not required), but if performed should show negative PET baseline, baseline lesions must show CR as disappearance of measurable and nonmeasurable nodal lesions (Nodal masses >1.5 cm in GTD at baseline must have regressed to =l.5 cm GTD, nodes that were 1.1 to 1.5 cm [long axis] and >1.0 cm [short axis] must have decreased to 1.0 cm in their short axis, spleen and/or liver must be normal size, if tested) and no new lesions.	First infusion date of brexucabtagene autoleucel (Phase 2) to data cutoff date of 09 September 2020 (Maximum duration: 23 Months)
Secondary	Phase 2: Overall Survival (OS)	OS was defined as the time from brexucabtagene autoleucel infusion to the date of death from any cause. Participants who had not died by the analysis data cutoff date were censored at their last contact date. KM estimates was used for analyses.	First infusion date of brexucabtagene autoleucel (Phase 2) to death or data cutoff date of 09 September 2020 (Maximum duration: 23 Months)
Secondary	Phase 2: Relapse-free Survival (RFS)	RFS: time from brexucabtagene autoleucel infusion to date of disease relapse or death from any cause. Participants not meeting criteria for relapse by the analysis data cutoff date were censored at their last evaluable disease assessment date. Participants who had not achieved a CR or CRi at analysis data cutoff were evaluated as an RFS event at Day 0. CR and CRi are defined in Outcome Measures 4 and 5. Relapse is defined in Outcome Measure 6. KM estimates was used for analyses.	First infusion date of brexucabtagene autoleucel (Phase 2) to relapse/death or data cutoff date of 09 September 2020 (Maximum duration: 23 Months)
Secondary	Phase 2: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)	An AE was any untoward medical occurrence in a participant after brexucabtagene autoleucel infusion, which did not necessarily have a causal relationship with the treatment. An AE could therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. TEAEs included all AEs with onset on or after initiation of the brexucabtagene autoleucel infusion.	First infusion date of brexucabtagene autoleucel (Phase 2) to data cutoff date of 09 September 2020 (Maximum duration: 23 Months)
Secondary	Phase 2: Number of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value	Grading categories are determined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.	First infusion date of brexucabtagene autoleucel (Phase 2) to data cutoff date of 09 September 2020 (Maximum duration: 23 Months)
Secondary	Phase 2: Number of Participants Experiencing Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Decreased Parameter Value	Grading categories are determined by CTCAE version 4.03.	First infusion date of brexucabtagene autoleucel (Phase 2) to data cutoff date of 09 September 2020 (Maximum duration: 23 Months)
Secondary	Phase 2: Percentage of Participants With Anti-KTE-X19 Antibodies		First infusion date of brexucabtagene autoleucel (Phase 2) to data cutoff date of 09 September 2020 (Maximum duration: 23 Months)
Secondary	Phase 2: Number of Participants With 5-Level European Quality of Life-5 Dimensions (EQ-5D-5L): Health Utility Index Scale	EQ-5D-5L is a self-reported questionnaire used for assessing the overall health status of a participant scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was divided into 5 levels of severity: "No problem", "Slight problems", "Moderate problems", "Severe problems", and "Extreme problems" or "Unable to".	Baseline, Day 28, Month 3, Month 6, Month 9, Month 12
Secondary	Phase 2: Change From Baseline Over Time in EQ-5D: Visual Analogue Scale (VAS)	EQ-5D is a self-reported questionnaire used for assessing the overall health status of a participant. The EQ-5D-VAS records the participant's self-rated health on a 20-cm vertical visual analogue scale and is asked to make a global assessment of their current state of health with 0 indicating the worst health they can imagine and 100 indicating the best health they can imagine.	Baseline, Day 28, Month 3, Month 6, Month 9, Month 12

External Links

•   Gilead Clinical Trials Website