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Relapsed/Refractory Chronic Lymphocytic Leukemia and Relapsed/Refractory Small Lymphocytic LymphomaPhase 1ZUMA-8NCT03624036

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 study testing brexucabtagene autoleucel, Fludarabine and Cyclophosphamide in people with Relapsed/Refractory Chronic Lymphocytic Leukemia and Relapsed/Refractory Small Lymphocytic Lymphoma, run by Kite, A Gilead Company at 22 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
brexucabtagene autoleucel, Fludarabine and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
22 sitesin 2 countries
Study dates
15 Nov 2018to 18 Nov 2022
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Documentation of relapsed or refractory CLL and SLL; must have received at least 2 prior lines of treatment, one of which must include a Bruton's tyrosine kinase (BTK) inhibitor.
  • Cohort 1 and 2: Participants with r/r CLL who have received at least 2 prior lines of treatment, one of which must include a BTK inhibitor.
  • Cohort 3: Participants with r/r CLL and SLL must present with ≤ 1% circulating tumor cells in peripheral blood or absolute lymphocyte count (ALC) < 5000 cells/μL. Participants must have received at least 2 prior lines of treatment, one of which must include a BTK inhibitor.
  • Cohort 4: Participants with r/r CLL who have received at least 2 prior lines of treatment and must have received ibrutinib as a single agent or in comibation with anti-cluster of differentiate 20 (CD20) antibodies, B-cell lymphoma 2 (BCL-2) inhibitors, and phosphoinositide 3-kinase inhibitor (PI3k) inhibitors for at least 6 months as the last line of therapy prior to screening. Ibrutinib administration will continue up to 30 hours prior to leukapheresis. In case of treatment interruption with ibrutinib, the principal investigator should reach out to the medical monitor to discuss.
  • An indication for treatment per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria and radiographically measurable disease (at least 1 lesion > 1.5 cm in diameter)
  • Adequate hematologic function as indicated by:
Show all 18Show fewer
  • Platelet count ≥ 50 × 10^9/L
  • Neutrophil count ≥ 0.5 × 10^9/L
  • Hemoglobin ≥ 8 g/dL unless lower values are attributable to CLL
  • Adequate renal, hepatic, cardiac and pulmonary function defined as:
  • Creatinine clearance (as estimated by Cockcroft-Gault) ≥ 60 mL/min
  • Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 mg/dL unless participant has Gilbert's syndrome
  • Left ventricular ejection fraction (LVEF) ≥ 50%, no evidence of pericardial effusion, no New York Heart Association (NYHA) class III or IV functional classification, no clinically significant arrhythmias
  • No clinically significant pleural effusion
  • Baseline oxygen saturation > 92% on room air
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy or BTKi (ibrutinib or acalabrutinib) at the time the participant is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy. At least 3 half-lives must have elapsed from any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy at the time the participant is planned for leukapheresis (eg, ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists)

Who cannot join

  • A history of treatment including any of the following:
  • Prior cluster of differentiate 19 (CD19) directed therapy
  • Prior allogeneic hematopoietic stem cell transplant (SCT) or donor lymphocyte infusion (DLI) within 6 months prior to enrollment
  • History of autoimmune disease resulting in end-organ injury unless attributable to CLL (eg, idiopathic thrombocytopenic purpura (ITP), autoimmune hemolytic anemia (AIHA))
  • Diagnosis of Richter's transformation or a history of malignancy other than non-melanoma skin cancer or carcinoma in situ (eg, skin, cervix, bladder, breast), superficial bladder cancer, asymptomatic localized low grade prostate cancer for which watch-and-wait approach is standard of care, or any other cancer that has been in remission for > 3 years prior to enrollment
  • History of severe hypersensitivity reaction attributed to aminoglycosides
  • Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial locations and contacts

22 sites in 2 countries.

22 sites in 2 countries

United States21 sites

  • Emory University

    Atlanta, Georgia, 30322

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Cleveland Clinic - Taussig Cancer Institute

    Cleveland, Ohio, 44195

  • Ohio State University

    Columbus, Ohio, 43210

  • Baylor Cancer Hospital

    Dallas, Texas, 75246

  • Sarah Cannon - Denver

    Denver, Colorado, 80218

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of California Los Angeles (UCLA)

    Los Angeles, California, 90095

  • Sarah Cannon Research Center

    Nashville, Tennessee, 37203

  • Vanderbilt University

    Nashville, Tennessee, 37232

  • Memorial Sloan-Kettering

    New York, New York, 10021

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Mayo Clinic - Arizona

    Phoenix, Arizona, 85054

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of Rochester

    Rochester, New York, 14642

  • Swedish Cancer Institute

    Seattle, Washington, 98104

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Stanford University

    Stanford, California, 94035

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • University of Kansas Cancer Center

    Westwood, Kansas, 66205

Other trials in United States

Italy1 site

  • IRCCS Ospedale San Raffaele

    Milan, 20132

Other trials in Italy

About this study

Official title: 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

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).

Being tested
brexucabtagene autoleucel, Fludarabine, Cyclophosphamide
Medical subject headings
Recurrence, Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • brexucabtagene autoleucelBiological

    Also called KTE-X19

    CAR-transduced autologous T cells administered intravenously

  • FludarabineDrug

    Administered intravenously

  • CyclophosphamideDrug

    Administered intravenously

Study groups in NCT03624036
Study groupRoleWhat they receive
First Stage Cohort 1: 1 x 10^6 Anti-CD19 CAR T Cells/kgExperimentalParticipants 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.
Receives: Biological: brexucabtagene autoleucel; Drug: Fludarabine; Drug: Cyclophosphamide
First Stage Cohort 2: 2 x 10^6 Anti-CD19 CAR T Cells/kgExperimentalParticipants 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.
Receives: Biological: brexucabtagene autoleucel; Drug: Fludarabine; Drug: Cyclophosphamide
Second Stage Cohort 3: 1 x 10^6 Anti-CD19 CAR T Cells/kgExperimentalParticipants 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.
Receives: Biological: brexucabtagene autoleucel; Drug: Fludarabine; Drug: Cyclophosphamide
Second Stage Cohort 4A: 1 x 10^6 Anti-CD19 CAR T Cells/kgExperimentalParticipants 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.
Receives: Biological: brexucabtagene autoleucel; Drug: Fludarabine; Drug: Cyclophosphamide
Second Stage Cohort 4B: 2 x 10^6 Anti-CD19 CAR T Cells/kgExperimentalParticipants 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.
Receives: Biological: brexucabtagene autoleucel; Drug: Fludarabine; Drug: Cyclophosphamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Experiencing Dose Limiting Toxicities (DLTs)

    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.

    Measured: First infusion date of brexucabtagene autoleucel up to 28 days. Participants were evaluated in specified period but Grade 4 hematologic toxicity (specified in description) having onset in this period were further observed for 30 days for confirmation.

Secondary outcomes (3)

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

    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.

    Measured: First infusion date up to last follow up visit (maximum duration: 42 months)

  2. Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs)

    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.

    Measured: First infusion date up to last follow up visit (maximum duration: 42 months)

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

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

    Measured: First infusion date up to 3 months post-infusion (approximately 3 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Aug 2018
  2. Study start15 Nov 2018
  3. Primary completion12 Feb 2021
  4. Study completion18 Nov 2022

Why it stopped: Development program terminated

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03624036
Sponsor's protocol ID
KTE-C19-108
Other IDs
2018-001923-38, 2018
Acronym
ZUMA-8
Status last verified
Oct 2023
First submitted
7 Aug 2018
Last updated
18 Nov 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Davids MS, Kenderian SS, Flinn I, Hill BT, Maris M, Ghia P, Byrne M, Bartlett NL, Pagel JM, Zheng Y, Kanska J, Zhang W, Granados E, Pinilla-Ibarz J. ZUMA-8: a phase 1 study of brexucabtagene autoleucel in patients with relapsed/refractory chronic lymphocytic leukemia. Blood. 2025 Aug 21;146(8):938-943. doi: 10.1182/blood.2024027460.

    PubMed 40209059

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing brexucabtagene autoleucel, Fludarabine and Cyclophosphamide in people with Relapsed/Refractory Chronic Lymphocytic Leukemia and Relapsed/Refractory Small Lymphocytic Lymphoma, run by Kite, A Gilead Company at 22 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in United States, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Experiencing Dose Limiting Toxicities (DLTs) (time frame: First infusion date of brexucabtagene autoleucel up to 28 days. Participants were evaluated in specified period but Grade 4 hematologic toxicity (specified in description) having onset in this period were further observed for 30 days for confirmation.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03624036, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2023.

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