Clinical Trial - NCT03331198

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

Recruiting

Sponsor: Juno Therapeutics, Inc.

Collaborators: Celgene Corporation

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03331198

Protocol Info

Short Description: Phase 1 JCAR017 in CLL or SLL
Long Description: An Open-Label, Phase 1 Safety and Phase 2 Randomized Study of JCAR017 in Subjects with Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (017004)
MGH Status: Open
Sponsor: JUNO Therapeutics
Disease Program: Lymphoma

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.




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.
Condition Title Intervention Phase
Leukemia, Lymphocytic, Chronic, B-Cell Lymphoma, Small Lymphocytic JCAR017 (lisocabtagene maraleucel) JCAR017 (lisocabtagene maraleucel) + ibrutinib Phase 1/Phase 2
Study Type Interventional
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)

Primary Outcome Measures

Phase 1 monotherapy arm: recommended dose [Time Frame: 28 days] [Designated as safety issue: ]

Phase 1 combination therapy arm: adverse events [Time Frame: Through post-treatment Month 24] [Designated as safety issue: ]

Phase 1 combination therapy arm: laboratory abnormalities [Time Frame: Through post-treatment Month 24] [Designated as safety issue: ]

Phase 2: rate of complete remission (CR) [Time Frame: Through post-treatment Month 24] [Designated as safety issue: ]


Secondary Outcome Measures

Phase 2: overall response rate [Time Frame: Through post-treatment Month 24] [Designated as safety issue: ]

Phase 2: minimal residual disease (MRD)-negative response rate [Time Frame: Through post-treatment Month 24] [Designated as safety issue: ]

Phase 2: adverse events [Time Frame: Through post-treatment Month 24] [Designated as safety issue: ]

Phase 2: laboratory abnormalities [Time Frame: Through post-treatment Month 24] [Designated as safety issue: ]

Phase 2: overall survival [Time Frame: Through post-treatment Month 24] [Designated as safety issue: ]

Phase 2: progression-free survival (PFS) [Time Frame: Through post-treatment Month 24] [Designated as safety issue: ]

Phase 2: PK [Time Frame: Through post-treatment Month 24] [Designated as safety issue: ]

Phase 2: PK [Time Frame: Through post-treatment Month 24] [Designated as safety issue: ]

Phase 2: PK [Time Frame: Through post-treatment Month 24] [Designated as safety issue: ]

Phase 2: health economics and outcomes research [Time Frame: Through post-treatment Month 24] [Designated as safety issue: ]

Phase 2: health-related quality of life [Time Frame: Through post-treatment Month 24] [Designated as safety issue: ]

Phase 2: health-related quality of life [Time Frame: Through post-treatment Month 24] [Designated as safety issue: ]

Estimated Enrollment: 200
Study Start Date: December 2017
Estimated Study Completion Date: March 2022
Estimated Primary Completion Date: December 2020
Arms Assigned Interventions

Experimental:Phase 1 JCAR017 monotherapy

Subjects will be assigned to receive JCAR017 (lisocabtagene maraleucel)
Biological:JCAR017 (lisocabtagene maraleucel)
Participants will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JCAR017. During JCAR017 production, participants may receive bridging chemotherapy for disease control. Upon successful generation of JCAR017 product, participants will receive treatment with JCAR017 therapy. Each cycle will include lymphodepleting chemotherapy followed by one dose of JCAR017 administered by intravenous (IV) injection.

Experimental:Phase 1 JCAR017 + ibrutinib

Subjects receiving ibrutinib at baseline will be assigned to receive JCAR017 (lisocabtagene maraleucel) at the recommended dose + ibrutinib
Biological:JCAR017 (lisocabtagene maraleucel) + ibrutinib
Participants eligible for this cohort should be receiving ibrutinib at the time of screening. For participants who previously discontinued ibrutinib, ibrutinib will be started at the time of enrollment. Ibrutinib treatment will continue for up to 90 days after JCAR017 infusion (or longer for participants who are receiving benefit from ibrutinib). Participants will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JCAR017. During JCAR017 production, participants may receive bridging chemotherapy for disease control. Upon successful generation of JCAR017 product, participants will receive treatment with JCAR017 therapy. Each cycle will include lymphodepleting chemotherapy followed by one dose of JCAR017 administered by intravenous (IV) injection.

Experimental:Phase 2 JCAR017 monotherapy

Subjects will receive JCAR017 (lisocabtagene maraleucel) at the recommended dose from the Phase 1 monotherapy arm

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03331198

Locations

  • United States, Arizona
    • Banner MD Anderson Cancer Center Gilbert, Arizona, United States, 85234
  • United States, California
    • City of Hope Duarte, California, United States, 91010
    • UC San Diego Moores Cancer Center La Jolla, California, United States, 92093
    • University of California San Francisco San Francisco, California, United States, 94143
  • United States, Illinois
    • Northwestern University Chicago, Illinois, United States, 60611
    • University of Chicago Medical Center Chicago, Illinois, United States, 60637
  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02114
    • Beth Israel Deaconess Medical Center Boston, Massachusetts, United States, 02215
  • United States, Nebraska
    • University of Nebraska Medical Center Omaha, Nebraska, United States, 68198
  • United States, New Jersey
    • Hackensack University Medical Center Hackensack, New Jersey, United States, 07601
  • United States, New York
    • Columbia University Medical Center New York, New York, United States, 10032
    • Weill Cornell Medical College New York, New York, United States, 10065
  • United States, Pennsylvania
    • Thomas Jefferson University Philadelphia, Pennsylvania, United States, 19107
    • UPMC Hillman Cancer Center Pittsburgh, Pennsylvania, United States, 15232
  • United States, Texas
    • The University of Texas MD Anderson Cancer Center Houston, Texas, United States, 77030
  • United States, Utah
    • Huntsman Cancer Institute Salt Lake City, Utah, United States, 84112
  • United States, Washington
    • Fred Hutchinson Cancer Research Center Seattle, Washington, United States, 98109

Sponsors and Collaborators

Juno Therapeutics, Inc.

Celgene Corporation

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03331198
Other Study ID Numbers: TRANSCEND-CLL-004
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Juno Therapeutics, Inc.:

JCAR017

chimeric antigen receptor

CLL

SLL

chronic lymphocytic leukemia

small lymphocytic lymphoma

CAR

CAR T cells

autologous T cell therapy

immunotherapy

Additional relevant MeSH terms:

Lymphoma

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on May 30, 2019