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Trial record 1 of 1 for:    NCT03744676
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A Safety Trial of Lisocabtagene Maraleucel (JCAR017) for Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL) in the Outpatient Setting (TRANSCEND-OUTREACH-007)

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ClinicalTrials.gov Identifier: NCT03744676
Recruitment Status : Recruiting
First Posted : November 16, 2018
Last Update Posted : February 18, 2021
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Juno Therapeutics, a Subsidiary of Celgene

Tracking Information
First Submitted Date  ICMJE November 7, 2018
First Posted Date  ICMJE November 16, 2018
Last Update Posted Date February 18, 2021
Actual Study Start Date  ICMJE November 29, 2018
Estimated Primary Completion Date October 30, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 15, 2018)
Adverse events [ Time Frame: Through Month 24 ]
Proportion of subjects experiencing cytokine release syndrome, neurotoxicity, prolonged cytopenias, infections AE of Grade 3 or higher
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 6, 2019)
  • Adverse events [ Time Frame: Through Month 24 ]
    Proportion of subjects experiencing all AEs and laboratory abnormalities
  • Adverse events [ Time Frame: Through Month 24 ]
    Median time to onset and to resolution of cytokine release syndrome and neurotoxicity of Grade 3 or higher
  • Adverse Events [ Time Frame: Through Month 24 ]
    Management of cytokine release syndrome and neurotoxicity
  • Adverse Events [ Time Frame: Through Month 24 ]
    Of subjects monitored in the outpatient setting, the proportion of subjects experiencing all AEs and laboratory abnormalities
  • Objective response rate (ORR) [ Time Frame: Through Month 24 ]
    Objective response rate (ORR [complete response + partial response]) according to the Lugano Classification
  • Complete response (CR) rate [ Time Frame: Through Month 24 ]
    Complete response rate according to the Lugano Classification
  • Duration of response (DOR) and duration of complete response (DoCR) [ Time Frame: Through Month 24 ]
    Each defined as time from first response to progressive disease (PD) or death
  • Progression-free Survival (PFS) [ Time Frame: Through Month 24 ]
    Time from infusion of lisocabtagene maraleucel to PD or death, whichever is earlier
  • Overall Survival (OS) [ Time Frame: Through Month 24 ]
    Defined as the time from infusion of lisocabtagene maraleucel to the date of death
  • Pharmacokinetics- Maximum concentration (Cmax) [ Time Frame: Through Month 24 ]
    Maximum concentration of lisocabtagene maraleucel
  • Pharmacokinetics- Time of the maximum concentration (Tmax) [ Time Frame: Through Month 24 ]
    Time to peak concentration of lisocabtagene maraleucel in the blood
  • Pharmacokinetics- area under the curve [ Time Frame: Through Month 24 ]
    Area under the curve of lisocabtagene maraleucel in blood
  • Health-related quality of life questionnaires [ Time Frame: Through Month 24 ]
    The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 is a validated quality of life measure applicable to subjects with any cancer diagnosis. It is composed of 30 items that address general physical symptoms, physical functioning, fatigue and malaise, and social and emotional functioning. Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher scores on symptom scales indicating worse symptoms.
  • Health-related quality of life questionnaires [ Time Frame: Through Month 24 ]
    The EuroQol-5D (EQ-5D) is a standardized measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L consists of the EQ-5D-5L descriptive system and the EQ Visual Analogue scale (EQ VAS). The descriptive system comprises dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems). The VAS rating scale is a vertical 20 cm visual analogue scale with the end points labeled best imaginable health state at the top and worst imaginable health state at the bottom having numeric values of 100 and 0 respectively. The participant is asked to indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the 5 dimensions.
  • Health economics and outcomes research [ Time Frame: Through Month 24 ]
    For subjects hospitalized post-treatement, the number of days the subjects were hospitalized, including the number of days that the subjects were in the Intensive Care Unit (ICU) and non-ICU ward
  • Health economics and outcomes research [ Time Frame: Through Month 24 ]
    The percentage of lisocabtagene maraleucel-treated subjects hospitalized post-treatment for each reason will be reported.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 15, 2018)
  • Adverse events [ Time Frame: Through Month 24 ]
    Proportion of subjects experiencing all AEs and laboratory abnormalities
  • Adverse events [ Time Frame: Through Month 24 ]
    Median time to onset and to resolution of cytokine release syndrome and neurotoxicity of Grade 3 or higher
  • Adverse Events [ Time Frame: Through Month 24 ]
    Management of cytokine release syndrome and neurotoxicity
  • Objective response rate (ORR) [ Time Frame: Through Month 24 ]
    Objective response rate (ORR [complete response + partial response]) according to the Lugano Classification
  • Complete response (CR) rate [ Time Frame: Through Month 24 ]
    Complete response rate according to the Lugano Classification
  • Duration of response (DOR) and duration of complete response (DoCR) [ Time Frame: Through Month 24 ]
    Each defined as time from first response to progressive disease (PD) or death
  • Progression-free Survival (PFS) [ Time Frame: Through Month 24 ]
    Time from infusion of lisocabtagene maraleucel to PD or death, whichever is earlier
  • Overall Survival (OS) [ Time Frame: Through Month 24 ]
    Defined as the time from infusion of lisocabtagene maraleucel to the date of death
  • Pharmacokinetics- Maximum concentration (Cmax) [ Time Frame: Through Month 24 ]
    Maximum concentration of lisocabtagene maraleucel
  • Pharmacokinetics- Time of the maximum concentration (Tmax) [ Time Frame: Through Month 24 ]
    Time to peak concentration of lisocabtagene maraleucel in the blood
  • Pharmacokinetics- area under the curve [ Time Frame: Through Month 24 ]
    Area under the curve of lisocabtagene maraleucel in blood
  • Health-related quality of life questionnaires [ Time Frame: Through Month 24 ]
    The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 is a validated quality of life measure applicable to subjects with any cancer diagnosis. It is composed of 30 items that address general physical symptoms, physical functioning, fatigue and malaise, and social and emotional functioning. Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher scores on symptom scales indicating worse symptoms.
  • Health-related quality of life questionnaires [ Time Frame: Through Month 24 ]
    The EuroQol-5D (EQ-5D) is a standardized measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L consists of the EQ-5D-5L descriptive system and the EQ Visual Analogue scale (EQ VAS). The descriptive system comprises dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems). The VAS rating scale is a vertical 20 cm visual analogue scale with the end points labeled best imaginable health state at the top and worst imaginable health state at the bottom having numeric values of 100 and 0 respectively. The participant is asked to indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the 5 dimensions.
  • Health economics and outcomes research [ Time Frame: Through Month 24 ]
    The number of days the patient was hospitalized post-treatment, including the number of days that the patient was in the Intensive Care Unit (ICU) and non-ICU
  • Health economics and outcomes research [ Time Frame: Through Month 24 ]
    The percentage of lisocabtagene maraleucel-treated subjects hospitalized post-treatment for each reason will be reported.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Safety Trial of Lisocabtagene Maraleucel (JCAR017) for Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL) in the Outpatient Setting (TRANSCEND-OUTREACH-007)
Official Title  ICMJE A Safety Trial of Lisocabtagene Maraleucel (JCAR017) for Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL) in the Outpatient Setting
Brief Summary This is an open-label, multicenter, Phase 2 study to determine the safety, PK, and efficacy of lisocabtagene maraleucel (JCAR017) in subjects who have relapsed from, or are refractory to, two lines of immunochemotherapy for aggressive B-cell non-Hodgkin lymphoma (NHL) in the outpatient setting. Subjects will receive treatment with JCAR017 and will be followed for up to 2 years.
Detailed Description

This is an open-label, multicenter, Phase 2 study to assess the safety and antitumor activity in adult patients with relapsed or refractory B-cell non-Hodgkin Lymphoma when administered with lisocabtagene maraleucel (JCAR017) in the outpatient setting.

Upon the successful product generation of lisocabtagene maraleucel, subjects will enter the treatment phase of the study. Treatment will include lymphodepleting chemotherapy followed by lisocabtagene maraleucel administration. Subjects will then enter the post-treatment follow-up phase of the study and will be followed for approximately 24 months for safety, disease status, health-related quality of life (HRQoL), and survival. Long-term follow-up will continue under a separate long-term follow-up protocol, per health regulatory authority guidelines, currently up to 15 years after the last lisocabtagene maraleucel administration.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Lymphoma, Non-Hodgkin
  • Lymphoma
  • Lymphoma, B-Cell
  • Lymphoma, Large B-Cell, Diffuse
  • Neoplasms
  • Neoplasms by Histologic Type
  • Lymphoproliferative Disorders
  • Lymphatic Diseases
  • Immunoproliferative Disorders
  • Immune System Disorder
Intervention  ICMJE Biological: lisocabtagene maraleucel
lisocabtagene maraleucel will be administered as single dose intravenous (IV) injection
Other Names:
  • JCAR017
  • liso-cel
Study Arms  ICMJE Experimental: Lisocabtagene maraleucel
Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of lisocabtagene maraleucel. During lisocabtagene maraleucel production, subjects may receive low-dose chemotherapy for disease control. Upon successful generation of lisocabtagene maraleucel product, subjects will receive treatment which will include lymphodepleting chemotherapy followed by one dose of lisocabtagene maraleucel administered by intravenous (IV) injection.
Intervention: Biological: lisocabtagene maraleucel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 6, 2019)
80
Original Estimated Enrollment  ICMJE
 (submitted: November 15, 2018)
50
Estimated Study Completion Date  ICMJE October 30, 2023
Estimated Primary Completion Date October 30, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age ≥ 18 years at the time of consent
  • Relapsed or refractory B-cell NHL of the following histologies: diffuse large B cell lymphoma (DLBCL) not otherwise specified; includes biopsy-confirmed transformed DLBCL from indolent histologies, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology, primary mediastinal B-cell lymphoma(PMBCL), and follicular lymphoma Grade 3B. Subjects must have been treated with an anthracycline and rituximab (or other CD20-targeted agent) and have relapsed or refractory disease after at least 2 systemic lines of therapy for DLBCL or after auto-HSCT.
  • Positron-emission tomography-positive disease by Lugano Classification
  • Eastern Cooperative Oncology Group performance status of 0 to 1
  • Adequate bone marrow, renal, hepatic, pulmonary, cardiac organ function
  • Adequate vascular access for leukapheresis procedure
  • Subjects who have received previous CD19-targeted therapy must have CD19-positive lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy
  • Subjects must agree to use appropriate contraception.

Exclusion Criteria:

  • Subjects with central nervous system (CNS)-only involvement by malignancy (note: subjects with secondary CNS involvement are allowed on study)
  • History of prior allogeneic hematopoietic stem cell transplant
  • Treatment with alemtuzumab within 6 months of leukapheresis, or treatment with fludarabine or cladribine within 3 months of leukapheresis
  • History of another primary malignancy that has not been in remission for at least 2 years.The following are examples of exceptions from the 2-year limit: nonmelanoma skin cancer, definitively-treated stage 1 solid tumor with a low risk of recurrence, curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on a Papanicolau smear.
  • Active hepatitis B or hepatitis C infection at the time of screening
  • History of or active human immunodeficiency virus infection at the time of screening
  • Uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate anti-infection treatment at the time of leukapheresis or lisocabtagene maraleucel administration
  • Presence of acute or chronic graft-versus-host disease
  • History of clinically significant cardiac conditions within the past 6 months
  • History or presence of clinically relevant CNS pathology such as epilepsy/seizure, paresis, aphasia, stroke, cerebral edema, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
  • Pregnant or nursing women
  • Subject does not meet protocol-specified washout periods for certain prior treatments
  • Prior CAR T-cell or other genetically modified T-cell therapy
  • Progressive vascular tumor invasion, thrombosis, or embolism
  • Venous thrombosis or embolism not managed on stable regimen of anticoagulation
  • Uncontrolled medical, psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol; or unwillingness or inability to follow the procedures required in the protocol
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03744676
Other Study ID Numbers  ICMJE 017007
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

Information relating to our policy on data sharing and the process for requesting data can be found at the following link:

https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: Analytic Code
Time Frame: See Plan Description
Access Criteria: See Plan Description
URL: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/
Responsible Party Juno Therapeutics, a Subsidiary of Celgene
Study Sponsor  ICMJE Juno Therapeutics, a Subsidiary of Celgene
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE
Study Director: Nick Trede, MD, PhD Juno Therapeutics, Inc.
PRS Account Juno Therapeutics, a Subsidiary of Celgene
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP