Clinical Trial 18329

Cancer Type: Malignant Hematology
Interventions:KTE-C19; cyclophosphamide; cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)

Study Type: Treatment
Phase of Study: Phase I/II
Investigators:

  • Bijal Shah

Overview

Study Title

A Phase 1/2 Multi-Center Study Evaluating the Safety and Efficacy of KTE-C19 in Adult Subjects with Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r ALL)

Summary

The purpose of this study is 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).

Objective

The Primary Objective of phase 1 is to evaluate the safety of KTE-C19. The Primary Objective of phase 2 is to evaluate the efficacy of KTE-C19, as measured by the overall complete remission rate defined as complete remission (CR) and complete remission with partial hematologic recovery (CRh) in adult subjects with r/r ALL. Secondary Objectives will include assessing the safety and tolerability of KTE-C19 and additional efficacy endpoints.

Inclusion Criteria

  • Relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL) defined as one of the following: Primary refractory disease; First relapse if first remission ≤ 12 months; Relapsed or refractory disease after first or later salvage therapy; Relapsed or refractory disease after allogeneic transplant provided participant is at least 100 days from stem cell transplant at the time of enrollment.
  • Morphological disease in the bone marrow (≥ 5% blasts)
  • Potential participants 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.
  • Age 18 or older
  • Eastern cooperative oncology group (ECOG) performance status of 0 or 1
  • Adequate renal, hepatic, pulmonary and cardiac function
  • In participants previously treated with blinatumomab, CD19 tumor expression in bone marrow or peripheral blood.

  • Exclusion Criteria

  • 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
  • Presence of central nervous system-3 (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.
  • 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 HIV, hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive)
  • 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 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 IBMTR index; acute or chronic GVHD requiring systemic treatment within 4 weeks prior to enrollment
  • Live vaccine ≤ 6 weeks prior to start of conditioning regimen
  • Women of child-bearing potential who are pregnant or breastfeeding.
  • Men and women 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
  • 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