Clinical Trials /

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

NCT02614066

Description:

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

Related Conditions:
  • Acute Lymphoblastic Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study Evaluating Brexucabtagene Autoleucel (KTE-X19) in Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (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 IDs

  • ORG STUDY ID: KTE-C19-103
  • SECONDARY ID: 2015-005009-35
  • NCT ID: NCT02614066

Conditions

  • Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
brexucabtagene autoleucel (KTE-X19)Single Arm
CyclophosphamideSingle Arm
FludarabineSingle Arm

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Single ArmExperimentalA conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously at a target dose of 2 x 10^6 anti-CD19 CAR+ T cells/kg or 1 x 10^6 anti-CD19 CAR+ T cells/kg
  • brexucabtagene autoleucel (KTE-X19)
  • Cyclophosphamide
  • Fludarabine

Eligibility Criteria

        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 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. Age 18 or older

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

          6. 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

          7. In individuals previously treated with blinatumomab, 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 HIV, hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV
             positive).

         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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)
Time Frame:Up to 28 days
Safety Issue:
Description:Dose-limiting toxicity is defined as protocol-defined brexucabtagene autoleucel (KTE-X19)-related events with onset within the first 28 days following brexucabtagene autoleucel (KTE-X19) infusion.

Secondary Outcome Measures

Measure:Duration of Remission
Time Frame:24 months
Safety Issue:
Description:Duration of Remission is defined as the time between their first complete response per indepedent review to relapse or any death in the absence of documented relapse
Measure:Minimum Residual Disease Negative Remission Rate
Time Frame:Up to 3 months
Safety Issue:
Description:Minimum residual disease negative remission rate is defined as incidence of a minimal residual disease response (MRD-). MRD- is defined as MRD < 10^(-4) per the standard assessment
Measure:Allogeneic Stem Cell Transplant Rate
Time Frame:Up to 24 months
Safety Issue:
Description:Allogeneic stem cell transplant rate is the incidence of Allogeneic SCT per the standard assessment
Measure:Overall Survival
Time Frame:Up to 15 years
Safety Issue:
Description:OS is defined as the time from brexucabtagene autoleucel (KTE-X19) infusion to the date of death from any cause
Measure:Relapse-free Survival (RFS)
Time Frame:Up to 24 months
Safety Issue:
Description:RFS is defined as the time from the brexucabtagene autoleucel (KTE-X19) infusion date to the date of disease relapse or death from any cause
Measure:Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Time Frame:Up to 15 years
Safety Issue:
Description:
Measure:Incidence of anti-KTE-X19 antibodies
Time Frame:Up to 15 years
Safety Issue:
Description:
Measure:Changes over time in the EQ-5D score and VAS score (Phase 2)
Time Frame:Up to 15 years
Safety Issue:
Description:The EQ-5D is a 2 page generic patient questionnaire for assessing the overall health status of a subject. The EQ-5D consists of a 5 dimension descriptive system including questions on mobility, selfcare, usual activities, pain/comfort, and anxiety/depression and a visual analogue scale (EQ VAS) which allows the respondent to record health on a vertical scale (eg, best health to worst health) thus allowing a quantitative measure of health outcome.
Measure:Percentage of Participants Experiencing Common Terminology Criteria for Adverse Events (CTCAE) Grade Changes in Safety Laboratory Values
Time Frame:Up to 15 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Kite, A Gilead Company

Last Updated

June 28, 2021