Clinical Trials /

Study Evaluating Safety and Efficacy of JCAR017 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)

NCT03331198

Description:

This is a Phase 1/2, open-label, multicenter study to determine the efficacy and safety of JCAR017 in adult subjects with relapsed or refractory CLL or SLL. The study will include a Phase 1 part to determine the recommended dose of JCAR017 monotherapy in subjects with relapsed or refractory CLL or SLL, followed by a Phase 2 part to further assess the efficacy and safety of JCAR017 monotherapy treatment at the recommended dose. A separate Phase 1 cohort will assess the combination of JCAR017 and concurrent ibrutinib. In all subjects, the safety, efficacy, and pharmacokinetics (PK) of JCAR017 will be evaluated.

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

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study Evaluating Safety and Efficacy of JCAR017 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
  • Official Title: An Open-Label, Phase 1/2 Study of JCAR017 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (017004)

Clinical Trial IDs

  • ORG STUDY ID: 017004
  • SECONDARY ID: TRANSCEND-CLL-004
  • NCT ID: NCT03331198

Conditions

  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Lymphoma, Small Lymphocytic

Interventions

DrugSynonymsArms
JCAR017 (lisocabtagene maraleucel)Phase 1 JCAR017 monotherapy
JCAR017 (lisocabtagene maraleucel) + ibrutinibPhase 1 JCAR017 + ibrutinib

Purpose

This is a Phase 1/2, open-label, multicenter study to determine the efficacy and safety of JCAR017 in adult subjects with relapsed or refractory CLL or SLL. The study will include a Phase 1 part to determine the recommended dose of JCAR017 monotherapy in subjects with relapsed or refractory CLL or SLL, followed by a Phase 2 part to further assess the efficacy and safety of JCAR017 monotherapy treatment at the recommended dose. A separate Phase 1 cohort will assess the combination of JCAR017 and concurrent ibrutinib. In all subjects, the safety, efficacy, and pharmacokinetics (PK) of JCAR017 will be evaluated.

Trial Arms

NameTypeDescriptionInterventions
Phase 1 JCAR017 monotherapyExperimentalSubjects will be assigned to receive JCAR017 (lisocabtagene maraleucel)
  • JCAR017 (lisocabtagene maraleucel)
Phase 1 JCAR017 + ibrutinibExperimentalSubjects receiving ibrutinib at baseline will be assigned to receive JCAR017 (lisocabtagene maraleucel) at the recommended dose + ibrutinib
  • JCAR017 (lisocabtagene maraleucel) + ibrutinib
Phase 2 JCAR017 monotherapyExperimentalSubjects will receive JCAR017 (lisocabtagene maraleucel) at the recommended dose from the Phase 1 monotherapy arm
  • JCAR017 (lisocabtagene maraleucel)

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of:

               1. CLL with an indication for treatment based on iwCLL guidelines and clinical
                  measurable disease, or

               2. SLL (lymphadenopathy and/or splenomegaly and < 5×10^9 CD19+ CD5+ clonal B
                  lymphocytes/L [< 5000/µL] in the peripheral blood at diagnosis with measurable
                  disease that is biopsy-proven SLL)

          -  Subjects (other than those in the ibrutinib + JCAR017 combination therapy arm) must
             have received and failed Bruton tyrosine kinase inhibitor (BTKi) treatment or have
             been deemed ineligible for BTKi therapy.

          -  Subjects (other than those in the ibrutinib + JCAR017 combination therapy cohort) must
             have received previous treatment as follows:

               1. Subjects with CLL or SLL and high-risk features must have failed at least 2 lines
                  of prior therapy.

               2. Subjects with CLL or SLL and standard-risk features must have failed at least 3
                  lines of prior therapy.

          -  Subjects in the ibrutinib + JCAR017 combination therapy cohort must either:

               1. be receiving ibrutinib and progressing at the time of study enrollment

               2. be receiving ibrutinib for at least 6 months with a response less than complete
                  response/remission (CR) and have high-risk features as defined in inclusion
                  criterion 5a

               3. have BTK or PLCgamma2 mutations per local laboratory assessment, with or without
                  progression on ibrutinib

               4. have previously received ibrutinib and have no contraindications to restarting
                  ibrutinib

          -  Eastern Cooperative Oncology Group performance status of ≤ 1

          -  Assessed by the Investigator to have adequate bone marrow function to receive
             lymphodepleting chemotherapy

          -  Adequate organ function, defined as:

               1. Serum creatinine ≤ 1.5 × age-adjusted upper limit of normal (ULN) OR calculated
                  creatinine clearance > 30 mL/min

               2. Alanine aminotransferase ≤ 5 × ULN and total bilirubin < 2.0 mg/dL (or < 3.0
                  mg/dL for subjects with Gilbert's syndrome or leukemic infiltration of the liver)

               3. Adequate pulmonary function, defined as ≤ Common Terminology Criteria for Adverse
                  Events (CTCAE) Grade 1 dyspnea and saturated oxygen (SaO2) ≥ 92% on room air

               4. Adequate cardiac function, defined as left ventricular ejection fraction ≥ 40% as
                  assessed by echocardiogram or multiple uptake gated acquisition scan performed
                  within 30 days prior to determination of eligibility

          -  Subject either currently has central vascular access or is a candidate to receive
             central vascular access or peripheral vascular access for leukapheresis procedure.

          -  If prior CD19-targeted therapy has been administered, subject must have CD19-positive
             disease confirmed by immunohistochemistry or flow cytometry since completing the prior
             CD19-targeted therapy.

        Exclusion Criteria:

          -  Subjects with known active central nervous system (CNS) involvement by malignancy.
             Those with prior CNS disease that has been effectively treated will be eligible if
             treatment was completed at least 3 months prior to enrollment with no evidence of
             symptomatic disease and stable abnormalities on repeat imaging.

          -  History of another primary malignancy that has not been in remission for at least 2
             years. (The following are exempt from the 2-year limit: nonmelanoma skin cancer,
             completely resected stage 1 solid tumor with low risk for recurrence, curatively
             treated localized prostate cancer, cervical carcinoma in situ on biopsy or a squamous
             intraepithelial lesion on Pap smear, and in situ breast cancer that has been
             completely resected.)

          -  Subjects with Richter's transformation

          -  Prior treatment with any gene therapy product

          -  Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV)
             infection

          -  Systemic fungal, bacterial, viral, or other infection that is not controlled

          -  Presence of acute or extensive chronic graft versus host disease (GVHD)

          -  History of any one of the following cardiovascular conditions within the past 6
             months: Class III or IV heart failure as defined by the New York Heart Association
             (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or
             other clinically significant cardiac disease

          -  History or presence of clinically relevant CNS pathology such as epilepsy, generalized
             seizure disorder, aphasia, stroke with current neurologic sequelae, severe brain
             injuries, dementia, Parkinson's disease, cerebellar disease,cerebral edema, or
             psychosis

          -  Pregnant or nursing (lactating) women

          -  Use of any of the following medications or treatments within the noted time prior to
             leukapheresis:

               1. Alemtuzumab within 6 months prior to leukapheresis

               2. Allogeneic hematopoietic stem cell transplant within 100 days prior to
                  leukapheresis

               3. Cladribine within 3 months prior to leukapheresis

               4. Donor lymphocyte infusions (DLI) within 2 months prior to leukapheresis

               5. Radiation including large bone marrow fields such as sternum or pelvis within 6
                  weeks prior to leukapheresis

               6. Fludarabine within 4 weeks prior to leukapheresis

               7. GVHD therapies such as calcineurin inhibitors, methotrexate or other
                  chemotherapeutics, mycophenolate mofetil, rapamycin, or immunosuppressive
                  antibodies (such as anti-tumor necrosis factor-α [TNFα], anti-interleukin-6
                  [IL-6], or anti-interleukin-6 receptor [IL 6R]) within 4 weeks prior to
                  leukapheresis

               8. Cyclophosphamide, ifosfamide, bendamustine, chlorambucil, or melphalan within 2
                  weeks prior to leukapheresis

               9. Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or
                  equivalent) within 7 days prior to leukapheresis

              10. Anti-CD20 monoclonal antibodies within 7 days prior to leukapheresis

              11. Venetoclax within 4 days prior to leukapheresis

              12. Idelalisib or duvelisib within 2 days prior to leukapheresis

              13. Lenalidomide within 1 day prior to leukapheresis

              14. Experimental agents, including off-label use of approved drugs (with the
                  exception of acalabrutinib which may be continued up to the day before
                  leukapheresis), within 4 weeks prior to leukapheresis unless progression is
                  documented on the experimental therapy and at least 3 half-lives have elapsed
                  prior to leukapheresis

          -  Uncontrolled medical, psychological, familial, sociological, or geographical
             conditions that do not permit compliance with the protocol, as judged by the
             Investigator; or subject unwillingness or inability to follow the procedures required
             in the protocol

          -  Tumor invasion of venous or arterial vessels

          -  Deep vein thrombosis or pulmonary embolism within 3 months prior to leukapheresis

          -  Deep vein thrombosis or pulmonary embolism requiring ongoing therapeutic
             anticoagulation
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1 monotherapy arm: recommended dose
Time Frame:28 days
Safety Issue:
Description:Recommended dose based on assessment of data from each dose level

Secondary Outcome Measures

Measure:Phase 2: overall response rate
Time Frame:Through post-treatment Month 24
Safety Issue:
Description:Overall response rate based on IRC assessment using iwCLL 2018 guidelines
Measure:Phase 2: minimal residual disease (MRD)-negative response rate
Time Frame:Through post-treatment Month 24
Safety Issue:
Description:MRD will be measured via IgHV deep sequencing and flow cytometry of peripheral blood and bone marrow
Measure:Phase 2: adverse events
Time Frame:Through post-treatment Month 24
Safety Issue:
Description:Proportion of subjects experiencing adverse events
Measure:Phase 2: laboratory abnormalities
Time Frame:Through post-treatment Month 24
Safety Issue:
Description:Proportion of subjects experiencing laboratory abnormalities
Measure:Phase 2: overall survival
Time Frame:Through post-treatment Month 24
Safety Issue:
Description:Overall survival
Measure:Phase 2: progression-free survival (PFS)
Time Frame:Through post-treatment Month 24
Safety Issue:
Description:PFS, defined as the time from JCAR017 infusion to disease progression or death
Measure:Phase 2: PK
Time Frame:Through post-treatment Month 24
Safety Issue:
Description:AUC of JCAR017 in blood and bone marrow
Measure:Phase 2: PK
Time Frame:Through post-treatment Month 24
Safety Issue:
Description:Cmax of JCAR017 in blood and bone marrow
Measure:Phase 2: PK
Time Frame:Through post-treatment Month 24
Safety Issue:
Description:Tmax of JCAR017 in blood and bone marrow
Measure:Phase 2: health economics and outcomes research
Time Frame:Through post-treatment Month 24
Safety Issue:
Description:EuroQol instrument EQ-5D-5L and numbers of intensive care unit (ICU) inpatient days and non-ICU inpatient days
Measure:Phase 2: health-related quality of life
Time Frame:Through post-treatment Month 24
Safety Issue:
Description:EORTC QLQ-C30
Measure:Phase 2: health-related quality of life
Time Frame:Through post-treatment Month 24
Safety Issue:
Description:CLL-specific module QLQ-CLL-17

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Juno Therapeutics, Inc.

Trial Keywords

  • JCAR017
  • chimeric antigen receptor
  • CLL
  • SLL
  • chronic lymphocytic leukemia
  • small lymphocytic lymphoma
  • CAR
  • CAR T cells
  • autologous T cell therapy
  • immunotherapy

Last Updated

February 3, 2020