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Celgene has been hinting at JCAR017 CLL data for several months with the most recent comments by MA at Citi on 6Sep2018. Wells Fargo (WF) highlighted that the TRANSCEND CLL trial was upsized from n=205 to n=400 with primary endpoint changed from complete response (CR) to progression free survival (PFS).
Here is the excerpt from WF's report:
In the categories of adoptive cell therapy (ACT) and Immuno-oncology (IO), we identified several new CAR-T therapeutic trials, a meaningful CAR-T trial amendment and numerous PD-1 combination trials. Most meaningful, in our view, was a near doubling in patient numbers from 205 to 400 in Celgene’s (CELG) TRANSCEND CLL study of CD19 CAR-T therapeutic JCAR017 and a change in primary endpoint to progression free survival (PFS) from complete response (CR). Trial amendment may reflect, in our view, the competitive nature of the CD19 CAR-T category as well as the CLL market.
Here is JCAR017 CLL-related commentary from a post about ASH2018 during the Citi Fireside Chat.
What will – our expectation is that, there will be a CLL abstract that investors should pay attention to it.
Robyn Karnauskas
Okay.
Mark Alles
It’s quite exciting and something that if again, people know about CLL, you worry about some of the side effects of CAR T therapies, cytokine release, et cetera. These are again, the highly refractory pretreated patients and it’s early small numbers, but looks extremely encouraging.The CLL maybe upside even to our model and that would create a two indication opportunity for JCAR017.
H-125 was a part of the campaign. We’ll see whether or not there’s anything there. But as I started with, it’s irrelevant. bb2121 is so far ahead. We will advance it, as you know, in Phase III in the third plus line therapy. And I expect that the minute it’s commercially available, other trials will begin with BMTCN, other ECOG will do what they did with SWOG 777.
I mean, it’s just going to catch fire in the clinical development world and it will go very quickly to early lines of therapy. Even if we didn’t want to do it, it’s going to happen and we want to do it. So that’s a bit of a mosaic. I think those were important. Then after that I don’t know, because, of course, this is abstract season, so I know what – I know about our own stuff, there’s so much else that will come forward, I just I’m not sure.
The clinicaltrials.gov TRANSCEND CLL trial protocol is found below:
Study Evaluating Safety and Efficacy of JCAR017 in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
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 randomized part to assess JCAR017 monotherapy treatment versus standard of care. 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 or disease
Intervention/treatment
Phase
Leukemia, Lymphocytic, Chronic, B-CellLymphoma, Small Lymphocytic
Biological: JCAR017 (lisocabtagene maraleucel)Biological: JCAR017 (lisocabtagene maraleucel) + ibrutinibDrug: Standard of care
Phase 1Phase 2
Study Design
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Study Type :
Interventional (Clinical Trial)
Estimated Enrollment :
400 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Phase 1: subjects will be assigned to receive JCAR017, or JCAR017 + ibrutinib Phase 2: subjects will be randomized to receive JCAR017 or standard of care. Patients who receive standard of care may cross over to receive JCAR017 in the event of disease progression.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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)
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
Participants eligible for this cohort should be receiving ibrutinib at the time of screening, and ibrutinib treatment will continue. 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
Subjects will receive JCAR017 (lisocabtagene maraleucel) at the recommended dose from the Phase 1 monotherapy arm
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.
Active Comparator: Phase 2 control
Subjects will receive standard of care treatment
Drug: Standard of care
Participants will receive standard-of-care therapy. These participants may cross over to receive treatment with JCAR017 at the time of progression.
Outcome Measures
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Primary Outcome Measures :
Phase 1 monotherapy arm: recommended dose [ Time Frame: 28 days ]
Recommended dose based on assessment of data from each dose level
Phase 1 combination therapy arm: adverse events [ Time Frame: Through post-treatment Month 24 ]
Proportion of subjects experiencing adverse events
Phase 1 combination therapy arm: laboratory abnormalities [ Time Frame: Through post-treatment Month 24 ]
Proportion of subjects experiencing laboratory abnormalities
Phase 2: progression-free survival (PFS) [ Time Frame: Through post-randomization Month 24 ]
PFS, defined as the time from randomization to disease progression or death
Secondary Outcome Measures :
Phase 2: adverse events [ Time Frame: Through post-randomization Month 24 ]
Proportion of subjects experiencing adverse events
Phase 2: laboratory abnormalities [ Time Frame: Through post-randomization Month 24 ]
Proportion of subjects experiencing laboratory abnormalities
Phase 2: overall response rate [ Time Frame: Through post-randomization Month 24 ]
Overall response rate based on Independent Review Committee assessment using iwCLL 2018 guidelines
Phase 2: minimal residual disease (MRD)-negative response rate [ Time Frame: Through post-randomization Month 24 ]
MRD will be measured via IgHV deep sequencing and flow cytometry of peripheral blood and bone marrow
Phase 2: overall survival [ Time Frame: Through post-randomization Month 24 ]
Overall survival
Phase 2: complete response rate [ Time Frame: Through post-randomization Month 24 ]
Complete response rate based on Independent Review Committee assessment using iwCLL 2018 guidelines
Phase 2: PK [ Time Frame: Through post-randomization Month 24 ]
AUC of JCAR017 in blood and bone marrow
Phase 2: PK [ Time Frame: Through post-randomization Month 24 ]
Cmax of JCAR017 in blood and bone marrow
Phase 2: PK [ Time Frame: Through post-randomization Month 24 ]
Tmax of JCAR017 in blood and bone marrow
Phase 2: health-related quality of life and health economics and outcomes research [ Time Frame: Through post-randomization Month 24 ]
EuroQol instrument EQ-5D-5L Numbers of intensive care unit (ICU) inpatient days and non-ICU inpatient days
Phase 2: health-related quality of life and health economics and outcomes research [ Time Frame: Through post-randomization Month 24 ]
EORTC QLQ-C30 Numbers of intensive care unit (ICU) inpatient days and non-ICU inpatient days
Phase 2: health-related quality of life and health economics and outcomes research [ Time Frame: Through post-randomization Month 24 ]
CLL-specific module QLQ-CLL Numbers of intensive care unit (ICU) inpatient days and non-ICU inpatient days
Eligibility Criteria
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Information from the National Library of MedicineChoosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study:
18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Criteria
Inclusion Criteria:
Diagnosis of:
CLL with an indication for treatment based on iwCLL guidelines and clinical measurable disease, or
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:
Subjects with CLL or SLL and high-risk features must have failed at least 2 lines of prior therapy, including a BTKi.
Subjects with CLL or SLL and standard-risk features must have failed at least 3 lines of prior therapy, including a BTKi.
Subjects with CLL or SLL who are BTKi intolerant and have received < 6 months of BTKi therapy or are ineligible for BTKi must have failed at least 1 (high-risk) or 2 (standard-risk) other lines of non-BTKi therapy.
Subjects in the ibrutinib + JCAR017 combination therapy cohort must be either:
receiving ibrutinib and progressing at the time of study enrollment
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
have BTK or PLCgamma2 mutations per local laboratory assessment, with or without progression on 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:
Serum creatinine ≤ 1.5 × age-adjusted upper limit of normal (ULN) OR calculated creatinine clearance > 30 mL/min
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)
Adequate pulmonary function, defined as ≤ Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 dyspnea and saturated oxygen (SaO2) ≥ 92% on room air
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, paresis, aphasia, stroke with current neurologic sequelae, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, or psychosis
Pregnant or nursing (lactating) women
Use of any of the following medications or treatments within the noted time prior to leukapheresis:
Alemtuzumab within 6 months prior to leukapheresis
Allogeneic hematopoietic stem cell transplant within 100 days prior to leukapheresis
Cladribine within 3 months prior to leukapheresis
Donor lymphocyte infusions (DLI) within 2 months prior to leukapheresis
Radiation including large bone marrow fields such as sternum or pelvis within 6 weeks prior to leukapheresis
Fludarabine within 4 weeks prior to leukapheresis
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
Cyclophosphamide, ifosfamide, bendamustine, chlorambucil, or melphalan within 2 weeks prior to leukapheresis
Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or equivalent) within 7 days prior to leukapheresis
Anti-CD20 monoclonal antibodies within 7 days prior to leukapheresis
Venetoclax within 4 days prior to leukapheresis
Idelalisib within 2 days prior to leukapheresis
Lenalidomide within 1 day prior to leukapheresis
Experimental agents, including off-label use of approved drugs, 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
Contacts and Locations
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Information from the National Library of MedicineTo learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03331198