Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Dasatinib

Brexucabtagene autoleucel

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

3 pulses of oral dasatinib (100 mg daily) beginning on Day 4 (+up to 2 days) for 3 days (with 4 days off), repeated weekly. The weekly 3-day pulse schedule of dasatinib may continue for up to 3 months in subjects who continue to meet the dasatinib eligibility criteria and who do not meet off treatment/off study criteria

Alyssa M Kanega

Lindsay Danley

Lori Muffly, M.D.

To assess the feasibility of oral dasatinib pulses (3 consecutive days per week) during the first month following infusion of brexucabtagene autoleucel (Tecartus) in adults with relapsed or refractory B-cell acute lymphoblastic leukemia.

Study of Brexucabtagene Autoleucel Plus Dasatinib in Adults With Acute Lymphoblastic Leukemia

Phase 1b Study of Brexucabtagene Autoleucel Plus Dasatinib in Adults With Acute Lymphoblastic Leukemia

Feasibility of administering oral dasatinib pulses (3 consecutive doses per week) during the first month following Tecartus infusion. Feasibility will be defined as the ability of 8 out of 20 subjects to miss no more than one cycle (defined as one week of at least three consecutive days of dasatinib) within the first month following Tecartus infusion.

Defined by a description of adverse events and serious adverse events at least possibly related to dasatinib following CAR T cell therapy; it will include an analysis of the sequential toxicity boundaries in that the analysis does not lead to a pause in the study; further defined as no reports of suspected death on study.

The definitions for response are primarily based on the standardized response criteria defined by National Comprehensive Cancer Network (NCCN) Guidelines (NCCN, 2021 v.2).

PFS is defined as the time from the start of the investigational therapy to the date of radiographic progression

OS is defined as the time from the date of initial disease diagnosis to the date of death from any cause

Kite Pharma

Stanford University

Symptoms and General Pathology

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Antirheumatic Agents

Antibodies

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immunoglobulins

Ibrutinib

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Participants with relapsed/refractory (r/r) chronic lymphocytic leukemia (CLL) will receive conditioning chemotherapy (fludarabine 30 mg/m\^2/day over 30 minutes and cyclophosphamide 500 mg/m\^2/day over 30-60 minutes) on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10\^6 anti-cluster of differentiate 19 (CD19) chimeric antigen receptor (CAR) T cells/kg on Day 0.

Participants with r/r CLL will receive conditioning chemotherapy (fludarabine 30 mg/m\^2/day over 30 minutes and cyclophosphamide 500 mg/m\^2/day over 30-60 minutes) on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 2 x 10\^6 anti-CD19 CAR T cells/kg on Day 0.

Participants with r/r CLL and small lymphocytic lymphoma (SLL) with ≤1% malignant cells in peripheral blood or absolute lymphocyte count (ALC) \< 5,000 cells/μL will receive conditioning chemotherapy (fludarabine 30 mg/m\^2/day over 30 minutes and cyclophosphamide 500 mg/m\^2/day over 30-60 minutes) on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10\^6 anti-CD19 CAR T cells/kg on Day 0.

Participants with r/r CLL who previously received two lines of therapy along with ibrutinib with or without anti CD20 antibodies, B-cell lymphoma 2 (BCL-2) and Phosphoinositide 3-kinase (PI3k) inhibitors will receive ibrutinib up to 30 hours prior to leukapheresis along with conditioning chemotherapy (fludarabine 30 mg/m\^2/day over 30 minutes and cyclophosphamide 500 mg/m\^2/day over 30-60 minutes) on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10\^6 anti-CD19 CAR T cells/kg on Day 0.

Participants with r/r CLL who previously received two lines of therapy along with ibrutinib with or without anti CD20 antibodies, BCL-2 and PI3k inhibitors will receive ibrutinib up to 30 hours prior to leukapheresis along with conditioning chemotherapy (fludarabine 30 mg/m\^2/day over 30 minutes and cyclophosphamide 500 mg/m\^2/day over 30-60 minutes) on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 2 x 10\^6 anti-CD19 CAR T cells/kg on Day 0.

Upon completion of Cohort 4A, it was determined not to enroll participants in Cohort 4B.

CAR-transduced autologous T cells administered intravenously

brexucabtagene autoleucel

Kite Study Director

The primary objective of this study is to evaluate the safety and tolerability of brexucabtagene autoleucel (KTE-X19) in adults with relapsed/refractory chronic lymphocytic leukemia (r/r CLL) and small lymphocytic lymphoma (r/r SLL) who have received at least 2 prior lines of treatment, one of which must include a Bruton's tyrosine kinase (BTK) inhibitor.

After the end of KTE-C19-108, participants who received an infusion of brexucabtagene autoleucel will complete the remainder of the 15-year follow-up assessments in a separate Long-term Follow-up study, KT-US-982-5968 (NCT05041309).

Study to Evaluate the Safety and Tolerability of Brexucabtagene Autoleucel (KTE-X19) in People With Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

A Phase 1 Multicenter Study Evaluating the Safety and Tolerability of KTE-X19 in Adult Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

DLTs refer to toxicities with onset experienced during the first 28 days of study treatment that have been judged to be clinically significant and related to study treatment. DLTs evaluated may include with some exceptions: All brexucabtagene autoleucel related Grade 3 non-hematologic toxicities lasting for more than 7 days, Grade 4 non-hematologic toxicities regardless of duration, and Grade 4 hematologic toxicity lasting more than 30 days if not attributable to underlying disease.

ORR was defined as percentage of participants achieving either complete response (CR), complete response with incomplete hematopoetic recovery (CRi) or partial response (PR). Criteria for CR: no lymphadenopathy \>1.5 cm or hepatomegaly/splenomegaly, lymphocytes \<4000/microliters (μL), bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules, platelets ≥100,000/µL, hemoglobin ≥11 grams per deciliter (g/dL). CRi: All CR criteria were met except with platelet count \<100,000/μL, hemoglobin \<11 g/dL or neutrophil count \<500/μL. PR: ≥1 of these: ≥50% decrease in lymphocytes, lymphadenopathy, size of liver and spleen, 50% decrease in bone marrow infiltrates; and ≥1 of these: platelets ≥100,000/µL or ≥50% increase from Baseline, hemoglobin ≥11 g/dL or ≥50% increase from Baseline. Participants who did not meet criteria were considered nonresponders. 95% confidence interval (CI) was calculated by Clopper-Pearson method.

An AE is defined as any untoward medical occurrence in a clinical trial participant that does not necessarily have a relationship with study treatment or worsening of a pre-existing medical condition. TEAEs were defined as AEs with onset on or after the initiation of brexucabtagene autoleucel infusion.

Peak was defined as the maximum number of CAR T cells measured post-infusion.

Kite, A Gilead Company

All-Cause Mortality: All Enrolled Analysis Set included all the enrolled participants.

Adverse Events: Safety Analysis Set included all participants who were treated with any dose of brexucabtagene autoleucel.

Participants with r/r CLL received conditioning chemotherapy (fludarabine 30 mg/m\^2/day over 30 minutes and cyclophosphamide 500 mg/m\^2/day over 30-60 minutes) administered IV on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10\^6 anti-CD19 CAR T cells/kg administered IV on Day 0.

First Stage Cohort 1: 1 x 10^6 Anti-CD19 CAR T Cells/kg

Participants with r/r CLL received conditioning chemotherapy (fludarabine 30 mg/m\^2/day over 30 minutes and cyclophosphamide 500 mg/m\^2/day over 30-60 minutes) administered IV on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 2 x 10\^6 anti-CD19 CAR T cells/kg administered IV on Day 0.

First Stage Cohort 2: 2 x 10^6 Anti-CD19 CAR T Cells/kg

Participants with r/r CLL and SLL with ≤1% malignant cells in peripheral blood or ALC \< 5,000 cells/μL received conditioning chemotherapy (fludarabine 30 mg/m\^2/day over 30 minutes and cyclophosphamide 500 mg/m\^2/day over 30-60 minutes) administered IV on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10\^6 anti-CD19 CAR T cells/kg administered IV on Day 0.

Second Stage Cohort 3: 1 x 10^6 Anti-CD19 CAR T Cells/kg

Participants with r/r CLL who previously received two lines of therapy along with ibrutinib with or without anti CD20 antibodies, BCL-2 and PI3k inhibitors received ibrutinib up to 30 hours prior to leukapheresis along with conditioning chemotherapy (fludarabine 30 mg/m\^2/day over 30 minutes and cyclophosphamide 500 mg/m\^2/day over 30-60 minutes) administered IV on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10\^6 anti-CD19 CAR T cells/kg administered IV on Day 0.

Second Stage Cohort 4A: 1 x 10^6 Anti-CD19 CAR T Cells/kg

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Italy

Region of Enrollment

Safety Analysis Set included all participants who were treated with any dose of brexucabtagene autoleucel.

Medical Information

DLT Evaluable Set included all participants treated with the target brexucabtagene autoleucel dose and followed for at least 28 days.

Number of Participants Experiencing Dose Limiting Toxicities (DLTs)

All Treated Subjects Set included all participants who were treated with any dose of brexucabtagene autoleucel.

Objective Response Rate (ORR) Per Investigator Review Assessed by International Workshop on CLL (IWCLL) 2018 Criteria

Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)

Participants in the safety analysis set with available data were analyzed.

Peak Level of Anti-CD19 CAR T-Cells in Blood

Participants with relapsed/refractory (r/r) chronic lymphocytic leukemia (CLL) received conditioning chemotherapy (fludarabine 30 mg/m\^2/day over 30 minutes and cyclophosphamide 500 mg/m\^2/day over 30-60 minutes) administered intravenously (IV) on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10\^6 anti-cluster of differentiate 19 (CD19) chimeric antigen receptor (CAR) T cells/kg administered IV on Day 0.

Participants with r/r CLL and small lymphocytic lymphoma (SLL) with ≤1% malignant cells in peripheral blood or absolute lymphocyte count (ALC) \< 5,000 cells/μL received conditioning chemotherapy (fludarabine 30 mg/m\^2/day over 30 minutes and cyclophosphamide 500 mg/m\^2/day over 30-60 minutes) administered IV on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10\^6 anti-CD19 CAR T cells/kg administered IV on Day 0.

Participants with r/r CLL who previously received two lines of therapy along with ibrutinib with or without anti CD20 antibodies, B-cell lymphoma 2 (BCL-2) and Phosphoinositide 3-kinase (PI3k) inhibitors received ibrutinib up to 30 hours prior to leukapheresis along with conditioning chemotherapy (fludarabine 30 mg/m\^2/day over 30 minutes and cyclophosphamide 500 mg/m\^2/day over 30-60 minutes) administered IV on Days -5 to -3 with 2 rest days, followed by single infusion of brexucabtagene autoleucel 1 x 10\^6 anti-CD19 CAR T cells/kg administered IV on Day 0.

Overall Study

Hematologic Neoplasms

Axicabtagene ciloleucel

All participants who previously received axicabtagene ciloleucel (KTE-C19 ) in the parent study will be enrolled in this arm for long-term follow-up.

All participants who previously received brexucabtagene autoleucel (KTE-X19) in the parent study will be enrolled in this arm for long-term follow-up.

All participants who previously received KITE-585 in the parent study will be enrolled in this arm for long-term follow-up.

All participants who previously received KITE-718 in the parent study will be enrolled in this arm for long-term follow-up.

All participants who previously received KITE-439 in the parent study will be enrolled in this arm for long-term follow-up.

All participants who previously received KITE-222 in the parent study will be enrolled in this arm for long-term follow-up.

All participants who previously received KITE-363 in the parent study will be enrolled in this arm for long-term follow-up.

No investigational product will be administered

Axicabtagene Ciloleucel

Brexucabtagene Autoleucel

KITE-585

KITE-718

KITE-439

KITE-222

KITE-363

The goal of this clinical study is to learn more about the long-term safety, effectiveness and prolonged action of Kite study drugs, axicabtagene ciloleucel, brexucabtagene autoleucel, KITE-222, KITE-363, KITE-439, KITE-585, and KITE-718, in participants of Kite-sponsored interventional studies.

Long-term Follow-up Study for Participants of Kite-Sponsored Interventional Studies Treated With Gene-Modified Cells

Targeted AEs include late-onset targeted AEs suspected to be possibly related to gene-modified cells include neurologic disorders, autoimmune disorders, hematologic disorders, serious infections, and secondary malignancies.

Targeted SAEs include late-onset targeted SAEs suspected to be possibly related to gene-modified cells include neurologic disorders, autoimmune disorders, hematologic disorders, serious infections, and secondary malignancies.

The Tanner Pubertal Stage Scale is a measure of pubertal development (sexual maturation) in children and adolescents with components described for each sex, rated separately on a scale of stage one to stage five, with 1 for preadolescent and 5 for mature/adult.

Time to subsequent anticancer therapies will be assessed only per regulatory request or sponsor needs.

Survival status will be assessed as the length of time from the participant's first dose date of study drug to death during the study due to any cause or last date of being alive during the study. Survival status will be assessed only per regulatory request or sponsor needs.

Lymphoma, Mantle-Cell

Lymphoma, Non-Hodgkin

Mantle Cell Lymphoma

A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells/kg administered intravenously.

The goal of this study is to provide access to brexucabtagene autoleucel for patients diagnosed with a disease approved for treatment with brexucabtagene autoleucel, that is otherwise out of specification for commercial release.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Brexucabtagene Autoleucel Plus Dasatinib in Adults With Acute Lymphoblastic Leukemia	NCT05993949	Lymphoblastic L...	Dasatinib	18 Years -	Stanford University
Study to Evaluate the Safety and Tolerability of Brexucabtagene Autoleucel (KTE-X19) in People With Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma	NCT03624036	Relapsed/Refrac...	brexucabtagene ... Fludarabine Cyclophosphamid...	18 Years -	Gilead Sciences
Study to Evaluate the Safety and Tolerability of Brexucabtagene Autoleucel (KTE-X19) in People With Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma	NCT03624036	Relapsed/Refrac...	brexucabtagene ... Fludarabine Cyclophosphamid...	18 Years -	Gilead Sciences
Long-term Follow-up Study for Participants of Kite-Sponsored Interventional Studies Treated With Gene-Modified Cells	NCT05041309	Solid and Hemat...	Axicabtagene Ci... Brexucabtagene ... KITE-585 KITE-718 KITE-439 KITE-222 KITE-363	-	Gilead Sciences
Expanded Access Study for the Treatment of Patients With Commercially Out-of-Specification Brexucabtagene Autoleucel	NCT05776134	Mantle Cell Lym... Acute Lymphobla...	Brexucabtagene ...	18 Years -	Gilead Sciences
Study of Brexucabtagene Autoleucel Plus Dasatinib in Adults With Acute Lymphoblastic Leukemia	NCT05993949	Lymphoblastic L...	Dasatinib	18 Years -	Stanford University

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