Description:
The study will be conducted in compliance with the International Council for Harmonisation
(ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good
Clinical Practice (GCP) and applicable regulatory requirements.
This is a randomized, open-label, parallel-group, multi-center trial in adult subjects with
Relapsed or refractory (R/R) aggressive Non-Hodgkin lymphoma (NHL) to compare safety and
efficacy between the standard of care (SOC) strategy versus JCAR017 (also known as
lisocabtagene maraleucel or liso-cel). Subjects will be randomized to either receive SOC (Arm
A) or to receive JCAR017 (Arm B).
All subjects randomized to Arm A will receive Standard of care (SOC) salvage therapy (R-DHAP,
RICE or R-GDP) as per physician's choice before proceeding to High dose chemotherapy (HDCT)
and Hematopoietic stem cell transplant (HSCT).
Subjects from Arm A may be allowed to cross over and receive JCAR017 upon confirmation of an
EFS event.
Subjects randomized to Arm B will receive Lymphodepleting (LD) chemotherapy followed by
JCAR017 infusion.
Title
- Brief Title: A Study to Compare the Efficacy and Safety of JCAR017 to Standard of Care in Adult Subjects With High-risk, Transplant-eligible Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphomas
- Official Title: A Global Randomized Multicenter Phase 3 Trial of JCAR017 Compared to Standard of Care in Adult Subjects With High-risk, Second-line, Transplant-eligible Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphomas (TRANSFORM).
Clinical Trial IDs
- ORG STUDY ID:
JCAR017-BCM-003
- SECONDARY ID:
U1111-1213-1944
- SECONDARY ID:
2018-000929-32
- NCT ID:
NCT03575351
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Standard of Care | | Arm A - Standard of Care (SOC) |
Purpose
The study will be conducted in compliance with the International Council for Harmonisation
(ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good
Clinical Practice (GCP) and applicable regulatory requirements.
This is a randomized, open-label, parallel-group, multi-center trial in adult subjects with
Relapsed or refractory (R/R) aggressive Non-Hodgkin lymphoma (NHL) to compare safety and
efficacy between the standard of care (SOC) strategy versus JCAR017 (also known as
lisocabtagene maraleucel or liso-cel). Subjects will be randomized to either receive SOC (Arm
A) or to receive JCAR017 (Arm B).
All subjects randomized to Arm A will receive Standard of care (SOC) salvage therapy (R-DHAP,
RICE or R-GDP) as per physician's choice before proceeding to High dose chemotherapy (HDCT)
and Hematopoietic stem cell transplant (HSCT).
Subjects from Arm A may be allowed to cross over and receive JCAR017 upon confirmation of an
EFS event.
Subjects randomized to Arm B will receive Lymphodepleting (LD) chemotherapy followed by
JCAR017 infusion.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Arm A - Standard of Care (SOC) | Active Comparator | Subjects should receive SOC (R-DHAP, R-ICE or R-GDP) followed by HDCT (BEAM) and HSCT. Standard of care regimen will be administered as per investigator decision. | |
| Arm B - JCAR017 | Experimental | Lymphodepleting chemotherapy with intravenous (IV) fludarabine (30 mg/m2/day for 3 days) plus cyclophosphamide IV (300 mg/m2/day for 3 days) (flu/cy) concurrently followed by JCAR017 infusion. | |
Eligibility Criteria
Inclusion Criteria:
1. Subject is ≥ 18 years and ≤ 75 years of age at the time of signing the informed
consent form (ICF).
2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
3. Histologically proven diffuse large B-cell lymphoma (DLBCL) NOS (de novo or
transformed FL), high grade B-cell lymphoma with MYC and BCL2 and/or BCL6
rearrangements with DLBCL histology (double/triple-hit lymphoma [DHL/THL]) or
follicular lymphoma grade 3B. Enough tumor material must be available for confirmation
by central pathology.
4. Refractory or relapsed within 12 months from CD20 antibody and anthracycline
containing first line therapy.
5. [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET) positive lesion at
screening.
6. Adequate organ function
7. Participants must agree to use effective contraception
Exclusion Criteria:
1. Subjects not eligible for hematopoietic stem cell transplantation (HSCT).
2. Subjects planned to undergo allogeneic stem cell transplantation.
3. Subjects with T cell rich/histiocyte rich large B-cell lymphoma (THRBCL), primary
cutaneous large B-cell lymphoma, primary mediastinal B-cell lymphoma (PMBCL), EBV
(Epstein-Barr virus) positive DLBCL of the elderly and Burkitt lymphoma, transformed
indolent NHL except transformed FL.
4. Subjects with prior history of malignancies, other than aggressive R/R NHL, unless the
subject has been free of the disease for ≥ 2 years with the exception of the following
noninvasive malignancies:
- Basal cell carcinoma of the skin
- Squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix
- Carcinoma in situ of the breast
- Incidental histologic finding of prostate cancer (T1a or T1b using the TNM
[tumor, nodes, metastasis] clinical staging system) or prostate cancer that is
curative.
- Other completely resected stage 1 solid tumor with low risk for recurrence
5. Treatment with any prior gene therapy product.
6. Subjects who have received previous CD19-targeted therapy.
7. History of or active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
infection.
8. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection
(including tuberculosis) despite appropriate antibiotics or other treatment.
9. Active autoimmune disease requiring immunosuppressive therapy.
10. History of any one of the following cardiovascular conditions within the past 6 months
prior to signing the ICF: 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.
11. History or presence of clinically relevant central nervous system (CNS) pathology
12. Pregnant or nursing (lactating) women.
| Maximum Eligible Age: | 75 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Event-free survival (EFS) |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | Time from randomization to death from any cause, progressive disease (PD), as assessed by the independent review committee (IRC) or start of new antineoplastic therapy, whichever occurs first |
Secondary Outcome Measures
| Measure: | Complete response rate (CRR) |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | Percentage of subjects achieving a complete response (CR) according to the Lugano Classification assessed by the IRC |
| Measure: | Progression-free survival (PFS) |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | Time from randomization to PD, SD at 1st response assessment as per protocol schedule, as per IRC review or death from any cause, whichever occurs first |
| Measure: | Overall survival (OS) |
| Time Frame: | Approximately 4.5 years |
| Safety Issue: | |
| Description: | Time from randomization to time of death due to any cause |
| Measure: | Overall response rate (ORR) |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | Percentage of subjects achieving an objective response of partial response (PR) or better according to the Lugano Classification as assessed by IRC review |
| Measure: | Duration of response (DOR) |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | Time from first response to disease progression, start of new antineoplastic therapy or death from any cause |
| Measure: | PFS on next line of treatment (PFS-2) |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | Time from randomization to second objective disease progression or death from any cause, whichever is first. |
| Measure: | Adverse Events (AEs) |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | Type, frequency and severity of adverse events (AEs), serious adverse events (SAE), and laboratory abnormalities (overall and in clinical, histological and molecular subgroups) |
| Measure: | HRQoL parameters assessed by European Organisation for Research and Treatment of Cancer - Quality of Life C30 questionnaire (EORTC-QLQ-C30) |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | European Organisation for Research and Treatment of Cancer - Quality of Life C30 questionnaire: The EORTC QLQ-C30 questionnaire will be used as a measure of health-related quality of life. |
| Measure: | HRQoL parameters assessed by EQ-5D-5L |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | European Quality of Life-5 Dimensions health state classifier to 5 Levels questionnaire: EQ-5D is a standardized measure of health status developed by the EuroQol Group to provide a simple, generic measure of health for clinical and economic appraisal. |
| Measure: | HRQoL parameters assessed by FACT-Lym "Additional concerns" subscale |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | Functional Assessment of Cancer Therapy-Lymphoma "Additional concerns" subscale: Only the LYM subscale will be administered in this study. This scale addresses symptoms and functional limitations (15 item) that are important to lymphoma patients. |
| Measure: | Reasons for hospital resource utilization |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | Will be assessed based on reasons for hospitalization |
| Measure: | Rate of hematopoietic stem cell transplant (HSCT) |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | Rate of completion of HDCT and HSCT |
| Measure: | Frequency of hospital resource utilization |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | Will be assessed based on frequency of hospitalizations calculated as, inpatient days, intensive care unit (ICU) days, outpatient visits days |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Celgene |
Trial Keywords
- Non-Hodgkin Lymphomas
- DLBCL
- Efficacy
- Safety
- JCAR017
- Liso-cel
- High-Risk
- Relapsed
- Refractory
Last Updated
