Study Details

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).

Participation Requirements

Age

18 Years +

Sex

ALL

Healthy Volunteers

Medical Condition

Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia

Gender

N/A

Date

March 2016 - July 2022

Study Type

INTERVENTIONAL

Study Phase

PHASE1, PHASE2

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

H Lee Moffitt Cancer Center

Tampa, Florida, United States, 33612

Emory University

Atlanta, Georgia, United States, 30322

Loyola University

Chicago, Illinois, United States, 60153

University of Chicago

Chicago, Illinois, United States, 60637

University of MD Greenbaum Comprehensive Cancer Center

Baltimore, Maryland, United States, 21201

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02215

Mayo Clinic

Rochester, Minnesota, United States, 55905

Washington University School of Medicine

Saint 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

University of Rochester

New York, New York, United States, 14642

Sarah Cannon

Nashville, Tennessee, United States, 37203

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

Swedish Cancer Institute

Seattle, Washington, United States, 98104

Seattle Cancer Center

Seattle, Washington, United States, 98109

University Health Network - Princess Margaret

Toronto, Ontario, Canada, M5G 2M9

Institut Paoli Calmettes

Marseille, France, 13009

Hopital Saint Louis

Paris, France, 75010

Hopital Haut-Leveque

Pessac, France, 33604

Hopital Pontchaillou - CHU de Rennes - Service d'Hematologie

Rennes, France, 35033

Universitatsklinikum Frankfurt

Frankfurt, Germany, 60590

Klinikum der Universitat Munchen

München, Germany, 81377

Universitaetsklinikum Wuerzburg

Würzburg, Germany, 97080

Amsterdam UMC

Amsterdam, Netherlands, 1105 AZ

Erasmus MC

Rotterdam, Netherlands, 3015 CE

Universitair Medisch Centrum Utrecht

Utrecht, Netherlands, 3508 GA

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) (ZUMA-3)

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