A global randomized multicenter Phase 3 trial 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 (TRANSFORM)
- Conditions
- Aggressive Non-Hodgkin B-Cell Lymphomafast growing B-cell cancer of the lymph nodes1002532010025322
- Registration Number
- NL-OMON52699
- Lead Sponsor
- Celgene Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 5
Subjects must satisfy the following criteria to be enrolled in the study:
1. Subject is >= 18 years and <= 75 years of age at the time of signing the
informed consent form (ICF).
2. ECOG performance status <= 1.
3. Histologically proven diffuse large B-cell lymphoma (DLBCL) NOS (de novo or
transformed indolent NHL), high grade B-cell lymphoma with MYC and BCL2 and/or
BCL6 rearrangements with DLBCL histology (double/triple-hit lymphoma
[DHL/THL]), primary mediastinal (thymic) large B-cell lymphoma (PMBCL), T
cell/histiocyte-rich large B-cell lymphoma (THRBCL) or follicular lymphoma
grade 3B (FL3B). Enough tumor material must be available for confirmation by
central pathology.
4. Refractory (SD, PD, PR or CR with relapse before 3 months) or relapsed (CR
with relapse on or after 3 months) within 12 months from CD20 antibody and
anthracycline containing first-line therapy.
5. [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET) positive
lesion per Lugano criteria at screening (Deauville score 4 or 5_
6. Adequate organ function
7. Participants must agree to use effective contraception
Please refer to protocol for full inclusion criteria.
1. Subjects not eligible for hematopoietic stem cell transplantation (HSCT).
2. Subjects planned to undergo allogeneic stem cell transplantation.
3. Subjects with primary cutaneous large B-cell lymphoma, EBV (Epstein-Barr
virus) positive DLBCL of the elderly and Burkitt lymphoma or transformation
from chronic lymphocytic leukemia/small lymphocytic lymphoma (Richter
transformation)..
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 non-invasive 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. Subjects with active hepatitis B, or active hepatitis C are excluded.
Subjects with negative polymerase chain reaction (PCR) assay for viral
load for hepatitis B or C are permitted. Subjects positive for hepatitis B
surface antigen and/or anti-hepatitis B core antibody with negative viral
load are eligible and should be considered for prophylactic antiviral
therapy. Subjects with a history of or active human immunodeficiency
virus (HIV) are excluded.
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.
Please refer to protocol for full exclusion criteria.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Efficacy<br /><br><br /><br>* Event-free survival (EFS)<br /><br>The time from randomization to death from any cause, progressive disease (PD),<br /><br>failure to achieve complete response (CR) or partial response (PR) by 9 weeks<br /><br>post-randomization, or start of new antineoplastic therapy due to efficacy<br /><br>concerns, whichever occurs first. </p><br>
- Secondary Outcome Measures
Name Time Method <p>Key secondary endpoints:<br /><br><br /><br>Efficacy<br /><br><br /><br>• Complete response rate (CRR), defined as the proportion of subjects achieving<br /><br>a CR from randomization up to 3 years post-randomization. Subjects with unknown<br /><br>or missing response will be counted as non-responders in the analysis. Any<br /><br>responses after a start of a new antineoplastic therapy will not be considered.<br /><br>Responses after cross over will be analyzed descriptively;<br /><br>• Progression-free survival (PFS), defined as the time from randomization to PD<br /><br>or death from any cause, whichever occurs first;<br /><br>• Overall survival (OS), defined as the time from randomization to death due to<br /><br>any cause.<br /><br><br /><br><br /><br>For the other Secondary and Exploratory endpoints please refer to the section 2<br /><br>from the protocol.</p><br>