Clinical Trials /

Safety and Tolerability of Brexucabtagene Autoleucel (KTE-X19) in Adults With Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

NCT03624036

Description:

The primary objective of this study is to evaluate the safety and tolerability of brexucabtagene autoleucel (KTE-X19) in adults with relapsed/refractory chronic lymphocytic leukemia (r/r CLL) and small lymphocytic lymphoma (r/r SLL).

Related Conditions:
  • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety and Tolerability of Brexucabtagene Autoleucel (KTE-X19) in Adults With Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma
  • Official Title: A Phase 1 Multicenter Study Evaluating the Safety and Tolerability of KTE-X19 in Adult Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: KTE-C19-108
  • SECONDARY ID: 2018-001923-38
  • NCT ID: NCT03624036

Conditions

  • Relapsed/Refractory Chronic Lymphocytic Leukemia and Relapsed/Refractory Small Lymphocytic Lymphoma

Interventions

DrugSynonymsArms
brexucabtagene autoleucel (KTE-X19)brexucabtagene autoleucel (KTE-X19)
Fludarabinebrexucabtagene autoleucel (KTE-X19)
Cyclophosphamidebrexucabtagene autoleucel (KTE-X19)

Purpose

The primary objective of this study is to evaluate the safety and tolerability of brexucabtagene autoleucel (KTE-X19) in adults with relapsed/refractory chronic lymphocytic leukemia (r/r CLL) and small lymphocytic lymphoma (r/r SLL).

Trial Arms

NameTypeDescriptionInterventions
brexucabtagene autoleucel (KTE-X19)ExperimentalParticipants will receive conditioning chemotherapy (fludarabine and cyclophosphamide), followed by the investigational treatment, brexucabtagene autoleucel (KTE-X19).
  • brexucabtagene autoleucel (KTE-X19)
  • Fludarabine
  • Cyclophosphamide

Eligibility Criteria

        Key Inclusion Criteria:

          -  Documentation of relapsed or refractory CLL and SLL; must have received at least 2
             prior lines of treatment, one of which must include a Bruton's tyrosine kinase (BTK)
             inhibitor.

               -  Cohort 1 and 2: Subjects with r/r CLL who have received at least 2 prior lines of
                  treatment, one of which must include a BTK inhibitor.

               -  Cohort 3: Subjects with r/r CLL and SLL must present with ≤ 1% circulating tumor
                  cells in peripheral blood or ALC < 5000 cells/μL. Subjects must have received at
                  least 2 prior lines of treatment, one of which must include a BTK inhibitor.

               -  Cohort 4: Subjects with r/r CLL who have received at least 2 prior lines of
                  treatment and must have received ibrutinib as a single agent or in comibation
                  with anti-CD20 antibodies, BCL-2 inhibitors, and PI3k inhibitors for at least 6
                  months as the last line of therapy prior to screening. Ibrutinib administration
                  will continue up to 30 hours prior to leukapheresis. In case of treatment
                  interruption with ibrutinib, the principal investigator should reach out to the
                  medical monitor to discuss.

          -  An indication for treatment per IWCLL 2018 criteria and radiographically measurable
             disease (at least 1 lesion > 1.5 cm in diameter)

          -  Adequate hematologic function as indicated by:

               -  Platelet count ≥ 50 × 10^9/L

               -  Neutrophil count ≥ 0.5 × 10^9/L

               -  Hemoglobin ≥ 8 g/dL unless lower values are attributable to CLL

          -  Adequate renal, hepatic, cardiac and pulmonary function defined as:

               -  Creatinine clearance (as estimated by Cockcroft-Gault) ≥ 60 mL/min

               -  Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 2.5 x
                  upper limit of normal (ULN)

               -  Total bilirubin ≤ 1.5 mg/dL unless subject has Gilbert's syndrome

               -  Left ventricular ejection fraction (LVEF) ≥ 50%, no evidence of pericardial
                  effusion, no New York Heart Association (NYHA) class III or IV functional
                  classification, no clinically significant arrhythmias

               -  No clinically significant pleural effusion

               -  Baseline oxygen saturation > 92% on room air

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any
             prior systemic therapy or BTKi (ibrutinib or acalabrutinib) at the time the subject is
             planned for leukapheresis, except for systemic inhibitory/stimulatory immune
             checkpoint therapy. At least 3 half-lives must have elapsed from any prior systemic
             inhibitory/stimulatory immune checkpoint molecule therapy at the time the subject is
             planned for leukapheresis (eg, ipilimumab, nivolumab, pembrolizumab, atezolizumab,
             OX40 agonists, 4-1BB agonists)

        Key Exclusion Criteria:

          -  A history of treatment including any of the following:

               -  Prior CD19 directed therapy

               -  Prior allogeneic hematopoietic stem cell transplant (SCT) or donor lymphocyte
                  infusion (DLI) within 6 months prior to enrollment

          -  History of autoimmune disease resulting in end-organ injury unless attributable to CLL
             (eg, idiopathic thrombocytopenic purpura (ITP), autoimmune hemolytic anemia (AIHA))

          -  Diagnosis of Richter's transformation or a history of malignancy other than
             non-melanoma skin cancer or carcinoma in situ (eg, skin, cervix, bladder, breast),
             superficial bladder cancer, asymptomatic localized low grade prostate cancer for which
             watch-and-wait approach is standard of care, or any other cancer that has been in
             remission for > 3 years prior to enrollment

          -  History of severe hypersensitivity reaction attributed to aminoglycosides

        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:Incidence of Dose Limiting Toxicity (DLTs) in participants treated with brexucabtagene autoleucel (KTE-X19)
Time Frame:Within first 28 days following infusion
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Objective Response Rate (ORR) per Investigator Review
Time Frame:Up to 15 years
Safety Issue:
Description:Objective response rate is defined per the IWCLL 2018 criteria.
Measure:Incidence of Adverse Events (AEs)
Time Frame:Up to 15 years
Safety Issue:
Description:
Measure:Levels of Anti-CD19 CAR T-Cells in Blood
Time Frame:Up to 2 years
Safety Issue:
Description:

Details

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

Last Updated

May 19, 2021