LAST UPDATED
November 19, 2024
Clinicaltrials.gov ID
EudraCT ID
OVERVIEW
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) (ZUMA-3)
PROTOCOL 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).
View moreParticipation requirements
Age
18 years +
Sex
All
Healthy Volunteers
No
Age
18 years +
Sex
All
Healthy Volunteers
No
Study details
Medical Condition
Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia
Gender
N/A
Date
March 2016 - July 2022
Study Type
Interventional
Study Phase
Phase 1, Phase 2
Product
brexucabtagene autoleucel, Cyclophosphamide, Fludarabine
Eligibility information
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.
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 International Bone Marrow Transplant Registry (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.
Locations
Locations (33)
UC San Diego-Moores Cancer Center
La Jolla, California, United States, 92093
University of California Los Angeles (UCLA)
Los Angeles, California, United States, 90095
University of California Irvine Medical Center
Orange, California, United States, 92868
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
University of California San Francisco
San Francisco, California, United States, 94143
University of MD Greenbaum Comprehensive Cancer Center
Baltimore, Maryland, United States, 21201
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Washington University School of Medicine
St Louis, Missouri, United States, 63110
Mount Sinai Tisch Cancer Institute
New York, New York, United States, 10029
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
Baylor Charles A. Sammons Cancer Center
Dallas, Texas, United States, 75246
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
University Health Network - Princess Margaret
Toronto, Ontario, Canada, M5G 2M9
Hopital Pontchaillou - CHU de Rennes - Service d'Hematologie
Rennes, France, 35033
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