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AzTrials

Relapsed/Refractory B-precursor Acute Lymphoblastic LeukemiaPhase 1/2ZUMA-3NCT02614066

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)

A Phase 1/2 study testing brexucabtagene autoleucel, Cyclophosphamide and Fludarabine in people with Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia, run by Kite, A Gilead Company at 33 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
brexucabtagene autoleucel, Cyclophosphamide and Fludarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
125 participants
Where
33 sitesin 5 countries
Study dates
7 Mar 2016to 3 Nov 2023
Phase
Phase 1/2
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

  • 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
  • Morphological disease in the bone marrow (≥ 5% blasts)
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  • 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
  • Eastern cooperative oncology group (ECOG) performance status of 0 or 1
  • 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
  • In individuals previously treated with blinatumomab, cluster of differentiation 19 (CD19) tumor expression in bone marrow or peripheral blood.

Who cannot join

  • Diagnosis of Burkitt's leukemia/lymphoma according to World Health Organization (WHO) classification or chronic myelogenous leukemia lymphoid blast crisis
  • 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
  • Isolated extramedullary disease
  • 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
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  • History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome or any other known bone marrow failure syndrome
  • History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
  • History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment.
  • Primary immunodeficiency
  • Known infection with human immunodeficiency virus (HIV), hepatitis B (HBsAg positive) or hepatitis C virus.
  • Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management.
  • 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
  • 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
  • Acute GVHD grade II-IV by Glucksberg criteria or severity B-D by International Bone Marrow Transplant Registry (IBMTR) index; acute or chronic GVHD requiring systemic treatment within 4 weeks prior to enrollment
  • Live vaccine ≤ 4 weeks prior to enrollment
  • 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
  • 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)
  • 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
  • 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.

Trial locations and contacts

33 sites in 5 countries.

33 sites in 5 countries

United States22 sites

  • Emory University

    Atlanta, Georgia, 30322

  • University of MD Greenbaum Comprehensive Cancer Center

    Baltimore, Maryland, 21201

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Loyola University

    Chicago, Illinois, 60153

  • University of Chicago

    Chicago, Illinois, 60637

  • Baylor Charles A. Sammons Cancer Center

    Dallas, Texas, 75246

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • UC San Diego-Moores Cancer Center

    La Jolla, California, 92093

  • University of California Los Angeles (UCLA)

    Los Angeles, California, 90095

  • Sarah Cannon

    Nashville, Tennessee, 37203

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Mount Sinai Tisch Cancer Institute

    New York, New York, 10029

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • University of Rochester

    New York, New York, 14642

  • University of California Irvine Medical Center

    Orange, California, 92868

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • University of California San Francisco

    San Francisco, California, 94143

  • Swedish Cancer Institute

    Seattle, Washington, 98104

  • Seattle Cancer Center

    Seattle, Washington, 98109

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • H Lee Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

France4 sites

  • Institut Paoli Calmettes

    Marseille, 13009

  • Hopital Saint Louis

    Paris, 75010

  • Hopital Haut-Leveque

    Pessac, 33604

  • Hopital Pontchaillou - CHU de Rennes - Service d'Hematologie

    Rennes, 35033

Other trials in France

Germany3 sites

  • Universitatsklinikum Frankfurt

    Frankfurt, 60590

  • Klinikum der Universitat Munchen

    München, 81377

  • Universitaetsklinikum Wuerzburg

    Würzburg, 97080

Other trials in Germany

Netherlands3 sites

  • Amsterdam UMC

    Amsterdam, 1105 AZ

  • Erasmus MC

    Rotterdam, 3015 CE

  • Universitair Medisch Centrum Utrecht

    Utrecht, 3508 GA

Other trials in Netherlands

Canada1 site

  • University Health Network - Princess Margaret

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

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)

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).

Read the detailed 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

Being tested
brexucabtagene autoleucel, Cyclophosphamide, Fludarabine
Medical subject headings
Recurrence

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

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

  • CyclophosphamideDrug

    Administered intravenously.

  • FludarabineDrug

    Administered intravenously.

Study groups in NCT02614066
Study groupRoleWhat they receive
Phase 1: 2 x 10^6 Anti-CD19 CAR T Cells/kgExperimentalParticipants with relapsed or refractory B-precursor acute lymphoblastic leukemia (r/r B-ALL) will receive conditioning chemotherapy (fludarabine 25 mg/m^2 intravenously [IV] over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m^2 IV over 60 minutes on Day -2) following a single IV infusion of brexucabtagene autoleucel (KTE-X19) chimeric antigen receptor (CAR) transduced autologous T cells at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing > 100 kg, a maximum flat dose of 2 x 10^8 anti-CD19 CAR T cells/kg of body weight will be administered.
Receives: Biological: brexucabtagene autoleucel; Drug: Cyclophosphamide; Drug: Fludarabine
Phase 1: 1 x 10^6 Anti-CD19 CAR T Cells/kgExperimentalParticipants with r/r B-ALL will receive conditioning chemotherapy (fludarabine 25 mg/m^2 IV over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m^2 IV over 60 minutes on Day -2) following a single IV infusion of brexucabtagene autoleucel CAR transduced autologous T cells at a target dose of 1 x 10^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing > 100 kg, a maximum flat dose of 1 x 10^8 anti-CD19 CAR T cells/kg of body weight will be administered.
Receives: Biological: brexucabtagene autoleucel; Drug: Cyclophosphamide; Drug: Fludarabine
Phase 1: 0.5 x 10^6 Anti-CD19 CAR T Cells/kgExperimentalParticipants with r/r B-ALL will receive conditioning chemotherapy (fludarabine 25 mg/m^2 IV over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m^2 IV over 60 minutes on Day -2) following a single IV infusion of brexucabtagene autoleucel CAR transduced autologous T cells at a target dose of 0.5 x 10^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing > 100 kg, a maximum flat dose of 0.5 x 10^8 anti-CD19 CAR T cells/kg of body weight will be administered.
Receives: Biological: brexucabtagene autoleucel; Drug: Cyclophosphamide; Drug: Fludarabine
Phase 2: 1 x 10^6 Anti-CD19 CAR T Cells/kgExperimentalParticipants with r/r B-ALL will receive conditioning chemotherapy (fludarabine 25 mg/m^2 IV over 30 minutes on Day -4, Day -3, and Day -2 and cyclophosphamide 900 mg/m^2 IV over 60 minutes on Day -2) following a single IV infusion of brexucabtagene autoleucel CAR transduced autologous T cells at a target dose of 1 x 10^6 anti-CD19 CAR T cells/kg of body weight on Day 0. For participants weighing > 100 kg, a maximum flat dose of 1 x 10^8 anti-CD19 CAR T cells/kg of body weight will be administered.
Receives: Biological: brexucabtagene autoleucel; Drug: Cyclophosphamide; Drug: Fludarabine

What is being measured

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

  1. 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).

    Measured: 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

  2. 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/microliters (μL) and platelets(Plt) ≥100000/μL in peripheral blood(PB);central nervous system extramedullary disease(CNS EMD) of CNS-1(no detectable leukemia in cerebrospinal fluid[CSF]);Non-CNS baselineEMD:if present(images shows CR),if no(images not needed),if performed shows negative positron emission tomography(PET) baseline,baseline lesions shows CR as disappearance of measurable and nonmeasurable nodal lesions(Nodal masses >1.5 cm in greatest transverse diameter[GTD] at baseline have regressed to ≤l.5 cm GTD,nodes that were 1.1 to 1.5 cm[long axis] and >1.0 cm[short axis] have decreased to 1.0 cm in their short axis, spleen and/or liver must be normal size) and no new lesions.CRi:all CR criteria except in PB ANC≥1000/μL and Plt<100000/μL or ANC<1000/μL and Plt ≥100000/μL.95% confidence interval (CI) was calculated by Clopper-Pearson method.

    Measured: First infusion date of brexucabtagene autoleucel (Phase 2) up to 3.7 years

Secondary outcomes (16)

  1. 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. 95% CI was calculated by Clopper-Pearson method.

    Measured: First infusion date of brexucabtagene autoleucel (Phase 2) up to 3.7 years

  2. Phase 2: Complete Remission (CR) Rate Per Independent Review

    CR: ≤ 5% blasts by morphology in BM; ANC ≥ 1000/µL and Plt ≥ 100000/µL 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) and no new lesions. Percentage of participants with CR was reported. 95% CI was calculated by Clopper-Pearson method.

    Measured: First infusion date of brexucabtagene autoleucel (Phase 2) up to 3.7 years

  3. Phase 2: Complete Remission With Incomplete Hematologic Recovery (CRi) Rate Per Independent Review

    CRi: ≤ 5% blasts by morphology in BM; ANC ≥ 1000/µL and Plt < 100000/µL or ANC < 1000/µL and Plt ≥ 100000/µL 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. 95% CI was calculated by Clopper-Pearson method.

    Measured: First infusion date of brexucabtagene autoleucel (Phase 2) up to 3.7 years

  4. 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.

    Measured: From first CR or CRi (Phase 2) up to 3.7 years

  5. 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/µL and Plt ≥ 100000/µL 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/µL and Plt <100000/µL or ANC <1000/µL and Plt ≥100000/µL. 95% CI was calculated by Clopper-Pearson method.

    Measured: First infusion date of brexucabtagene autoleucel (Phase 2) up to 5 years

  6. Phase 2: Percentage of Participants With Allogeneic Stem Cell Transplant (Allo-SCT)

    Measured: First infusion date of brexucabtagene autoleucel (Phase 2) up to 5 years

  7. Phase 2: MRD Negative Remission 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/µL and Plt ≥ 100000/µL 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) and no new lesions. 95% CI was calculated by Clopper-Pearson method.

    Measured: First infusion date of brexucabtagene autoleucel (Phase 2) up to 3.7 years

  8. Phase 2: MRD Negative Remission 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/µL and Plt < 100000/µL or ANC < 1000/µL and Plt ≥ 100000/µL 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) and no new lesions. 95% CI was calculated by Clopper-Pearson method.

    Measured: First infusion date of brexucabtagene autoleucel (Phase 2) up to 3.7 years

  9. 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.

    Measured: First infusion date of brexucabtagene autoleucel (Phase 2) up to 5 years

  10. 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.

    Measured: First infusion date of brexucabtagene autoleucel (Phase 2) up to 3.7 years

  11. 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.

    Measured: Up to 5 years

  12. Phase 2: Number of Participants Experiencing Laboratory Toxicity Grade 3 or Higher TEAEs Resulting From Increased Parameter Value

    Grading categories are determined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1: mild, Grade 2: moderate, Grade 3: severe or medically significant, Grade 4: life-threatening.

    Measured: Up to 5 years

  13. Phase 2: Number of Participants Experiencing Laboratory Toxicity Grade 3 or Higher TEAEs Resulting From Decreased Parameter Value

    Grading categories are determined by CTCAE version 4.03. Grade 1: mild, Grade 2: moderate, Grade 3: severe or medically significant, Grade 4: life-threatening.

    Measured: Up to 5 years

  14. Phase 2: Percentage of Participants With Anti-KTE-X19 Antibodies

    Measured: First infusion date of brexucabtagene autoleucel (Phase 2) up to 2.7 years

  15. Phase 2: Number of Participants With 5-Level European Quality of Life-5 Dimensions (EQ-5D-5L): Health Utility Index Scale

    The EQ-5D-5 levels(EQ-5D-5L)is a standardized measure of health status of the participant that provides a simple, generic measure of health for clinical and economic appraisal.It is a self-reported questionnaire used to assess the overall health status of participant scoring 5 dimensions of health: mobility,self-care,usual activities,pain/discomfort and anxiety/depression.Each dimension has 5 levels:no problems,slight problems,moderate problems,severe problems,and extreme problems.EQ-5D health states, defined by the EQ-5D descriptive system, are converted into a single summary index by a formula that attaches values (called QOL utilities)to each of the levels in each dimension.EQ-5D Summary Index values range from -0.11(worst health) to 1.00(perfect health).This decision results in a 1-digit number that shows the level for that dimension. The digits for 5 dimensions can be combined to 5-digit number that show the participant's health.Higher scores of EQ-5D-5L indicate better health.

    Measured: Baseline, Day 28, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, and Month 24

  16. Phase 2: EQ-5D Visual Analogue Scale (VAS) Score

    EQ-5D is a self-reported questionnaire used for assessing the overall health status of a participant. The EQ-5D is a participant rated questionnaire to assess health-related quality of life in terms of a single index value. 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. Higher scores indicated a better health state.

    Measured: Baseline, Day 28, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, and Month 24

Timeline

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

  1. First posted25 Nov 2015 (estimated)
  2. Study start7 Mar 2016
  3. Primary completion23 Jul 2022
  4. Study completion3 Nov 2023

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
125 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02614066
Sponsor's protocol ID
KTE-C19-103
Other IDs
2015-005009-35, 2015
Acronym
ZUMA-3
Status last verified
Oct 2024
First submitted
23 Nov 2015
Last updated
19 Nov 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gileadclinicaltrials.com/transparency-policy#Commitment

Publications

  • 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 Cell Therapy [Abstract S1569]. The 23rd European Hematology Association (EHA) Congress 2018 14-17 June; Stockholm, Sweden.

  • 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]. Blood 2016;128 (22):1227.

  • 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 Leukemia (r/r ALL). European Society for Medical Oncology (ESMO) Congress 2016;Abstract 3713.

  • 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 With KTE-C19 (Anti-CD19 Chimeric Antigen Receptor [CAR] T Cells): Preliminary Results of the ZUMA-3 and ZUMA-4 Trials. Blood 2016;128 (22):2803.

  • 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 Results of Novel Safety Interventions [Abstract ALL-025]. Clinical lymphoma, myeloma & leukemia 2017;17:S253.

  • 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 Oncology (ESMO) Congress 2017.

  • 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 [Abstract P523]. The 22nd European Hematology Association (EHA) Congress 2017 22-25 June; Madrid, Spain.

  • 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 Lymphoblastic Leukemia (ALL) [Abstract]. J Clin Oncol 2019;37 (15):7006.

  • 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 PS945]. HemaSphere 2019;3 (S1):426.

  • 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 Treated with Prior Blinatumomab in ZUMA-3 [Abstract ALL-128]. Clinical lymphoma, myeloma & leukemia 2018;18 (Supplement 1):S184.

  • 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 Acute Lymphoblastic Leukemia. ASCO; 2018 01-05 June; Chicago, IL.

  • 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) [Abstract 612]. Blood 2017;130 (Supplement 1):888.

  • 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 leukemia (R/R ALL) [Abstract 3024]. American Society of Clinical Oncology (ASCO) Annual Meeting; 2017 02-06 June; Chicago, Illinois.

  • 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 256]. Biol Blood Marrow Transplant 2019;25 (3):S185.

  • 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]. Blood 2018;132 (Supplement 1):897.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing brexucabtagene autoleucel, Cyclophosphamide and Fludarabine in people with Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia, run by Kite, A Gilead Company at 33 sites in 5 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 15 inclusion and 28 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: finished, as of the sponsor's last update on 19 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in United States, France, Germany, Netherlands, Canada. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 29 Nov 2021). 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?

Phase 1: Percentage 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 GR4 hematologic toxicity (specified in description) having onset in this period were further observed for 30 days for confirmation). The study lists 2 primary outcomes in all. 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 NCT02614066, which also lists 19 linked publications.

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 19 Nov 2024; AzTrials last refreshed its copy on 7 Nov 2026.

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