Etude : TRANSFORM / JCAR017-BCM-003

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Type d'étude
Présentation de l'étude
Acronyme : TRANSFORM

Nom : JCAR017-BCM-003

Traitement :

Type d'étude : Ciblage moléculaire / Innovation thérapeutique

Dernière MÀJ : 06/09/2019
CIM10 - Localisation(s)
Informations principales
Titre : 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

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C85 - Lymphome non hodgkinien, de types autres et non précisés

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C82 - Lymphome folliculaire
Informations complémentaires
Schéma : 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.

Study arms:
- Active Comparator: Arm A - Standard of Care (SOC)
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.
Intervention: Drug: Standard of Care
- Experimental: Arm B - JCAR017
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.
Intervention: Genetic: JCAR017

Current primary outcome:
Event-free survival (EFS) [ Time Frame: Approximately 3 years ]
Time from randomization to death from any cause, progressive disease (PD), failure to achieve complete response (CR) or partial response (PR), or start of new antineoplastic therapy due to efficacy concerns, whichever occurs first

Current secondary outcomes:
- Complete response rate (CRR) [ Time Frame: Approximately 3 years ]
- Progression-free survival (PFS) [ Time Frame: Approximately 3 years ]
- Overall survival (OS) [ Time Frame: Approximately 4.5 years ]
- Overall response rate (ORR) [ Time Frame: Approximately 3 years ]
- Duration of response (DOR) [ Time Frame: Approximately 3 years ]
- PFS on next line of treatment (PFS-2) [ Time Frame: Approximately 3 years ]
- Adverse Events (AEs) [ Time Frame: Approximately 3 years ]
- 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 ]
- HRQoL parameters assessed by EQ-5D-5L [ Time Frame: Approximately 3 years ]
- HRQoL parameters assessed by FACT-Lym "Additional concerns" subscale [ Time Frame: Approximately 3 years ]
- Reasons for hospital resource utilization [ Time Frame: Approximately 3 years ]
- Rate of hematopoietic stem cell transplant (HSCT) [ Time Frame: Approximately 3 years ]
- Frequency of hospital resource utilization [ Time Frame: Approximately 3 years ]
- Hospital resource utilization (HRU) [ Time Frame: Approximately 3 years ]

Phase : III

Stade : NA

Critères d'inclusion
Critères de non-inclusion
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - Subject is ≥ 18 years and ≤ 75 years of age at the time of signing the informed consent form (ICF).
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
- 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. Enough tumor material must be available for confirmation by central pathology.
- Refractory or relapsed within 12 months from CD20 antibody and anthracycline containing first line therapy.
- [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET) positive lesion at screening.
- Adequate organ function
- Participants must agree to use effective contraception

Critères de non-inclusion : - Subjects not eligible for hematopoietic stem cell transplantation (HSCT).
- Subjects planned to undergo allogeneic stem cell transplantation.
- Subjects with, primary cutaneous large B-cell lymphoma, EBV (Epstein-Barr virus) positive DLBCL of the elderly and Burkitt lymphoma.
- 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
- Treatment with any prior gene therapy product.
- Subjects who have received previous CD19-targeted therapy.
- History of or active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
- Subjects with uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment.
- Active autoimmune disease requiring immunosuppressive therapy.
- 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.
- History or presence of clinically relevant central nervous system (CNS) pathology
- Pregnant or nursing (lactating) women.
Informations relatives au promoteur
Promoteur :
Type de sponsor : Industriel
United States – Summit, NJ 86 Morris Avenue Summit, NJ 07901

Coordonnateur :
Centre investigateur
Informations relatives aux investigateurs
Centre investigateur :
Centre Hospitalier Universitaire de Lille - 2 Avenue Oscar Lambret - 59000 LILLE

Investigateur :
Professeur Franck MORSCHHAUSER

Secrétariat de recherche

Ouverture de l'essai : OUVERT

MAJ : 05/07/2019