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A Phase 1/2 Multi-Center Study Evaluating the Safety and Efficacy of KTE-X19 in Pediatric and Adolescent Subjects with Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r ALL) or Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma (r/r NHL) (ZUMA-4)
Protocol Number:
Phase I/II
Patrick Brown
Johns Hopkins Kimmel Cancer Center in Baltimore
This is a single arm, open-label, multi-center, phase 1/2 study, to determine the safety and efficacy of KTE-C19, an autologous anti-CD19 chimeric antigen receptor (CAR)-positive T cell therapy, in relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL) in pediatric or adolescent subjects.
Ages Eligible for Study: 2 Years to 21 Years (Child, Adult) Sexes Eligible for Study: All Accepts Healthy Volunteers: No Inclusion Criteria:1.Relapsed or refractory B-precursor ALL defined as one of the following: ?Primary refractory disease?Relapsed or refractory disease after first or later salvage therapy?Relapsed or refractory disease after allogeneic transplant provided subject is at least 100 days from stem cell transplant at the time of enrollment2.Morphological disease in the bone marrow ( equal to 5% blasts)3.Subjects 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 TKIs4.Ages 2 to 21 at the time of Assent or Consent per IRB guidelines5.Lansky (age less than 16 years at the time of assent/consent) or Karnofsky (age equal to 16 years at the time of assent/consent) performance status equal to 80 at screening6.Adequate renal, hepatic, pulmonary and cardiac function defined as: ?Creatinine clearance equal to 60 cc/min?Serum ALT/AST equal to 2.5 x ULN?Total bilirubin equal to 1.5 x ULN?Cardiac ejection fraction equal to 50% and no clinically significant ECG findings?Baseline oxygen saturation greater than 92% on room airExclusion Criteria1.Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification or chronic myelogenous leukemia lymphoid blast crisis2.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 years3.Presence of CNS-3 disease and CNS-2 disease with neurological changes4.History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome or any other known bone marrow failure syndrome5.History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment6.History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment.7.Primary immunodeficiency8.Known infection with HIV, hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive)9.Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management.10.Prior medication: ?Prior CD19 directed therapy, including CAR+ T cell, BiTE, and antibody drug conjugate (ADC), with the exception of subjects who received KTE-C19 in this study and are eligible for re-treatment?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 GVHD within 4 weeks prior to enrollment11.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 enrollment12.Live vaccine equal to 6 weeks prior to start of conditioning regimen13.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 are not considered to be of childbearing potential14.Subjects 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 KTE-C19
Experimental: Single Arm A 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
Last Update
08/08/2020 05:02 AM