Etude : ZUMA-7 /

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Type d'étude
Présentation de l'étude
Acronyme : ZUMA-7

Nom :

Traitement :

Type d'étude : Ciblage moléculaire / Innovation thérapeutique

Dernière MÀJ : 06/09/2019
CIM10 - Localisation(s)
Informations principales
Titre : A Phase 3, Randomized, Open-Label Study Evaluating Efficacy of Axicabtagene Ciloleucel Versus Standard of Care Therapy in Subjects With Relapsed/Refractory Diffuse Large B Cell Lymphoma

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C85 - Lymphome non hodgkinien, de types autres et non précisés
Informations complémentaires
Schéma : This is a phase 3 randomized, open-label, multicenter study evaluating the efficacy of axicabtagene ciloleucel versus standard of care therapy in subjects with relapsed/refractory DLBCL. Adult subjects with relapsed/refractory DLBCL after first-line rituximab and anthracycline-based chemotherapy will be randomized in a 1:1 ratio to receive axicabtagene ciloleucel or standard of care second-line therapy.

Standard of care will consist of a protocol-defined, platinum-based salvage combination chemotherapy regimen followed by high-dose therapy and autologous stem cell transplant in those who respond to salvage chemotherapy.

Primary outcome:
Event Free Survival (Time Frame: Up to 5 years). Event free survival is defined as the time from randomization to the earliest date of disease progression per Lugano Classification (Cheson et al, 2014), commencement of new lymphoma therapy, or death from any cause as determined by blinded central review.

Secondary outcomes:
- Objective Response Rate (ORR) (Time Frame: Up to 5 years)
- Objective response rate is defined as the incidence of either a complete response or a partial response by the Lugano Classification (Cheson et al, 2014) as determined by blinded central review
- Overall Survival (Time Frame: Up to 5 years)
- Overall survival is defined as the time from randomization to death from any cause

Study arms:
- Experimental: Axicabtagene Ciloleucel Treatment
Biological: Axicabtagene Ciloleucel
Drug: Cyclophosphamide
Drug: Fludarabine

- Active Comparator: Standard of Care Therapy
Intervention: Drug: Platinum-containing salvage chemotherapy (eg, R-ICE) followed by high dose therapy (eg, BEAM) and autologous stem cell transplant in responders.

- Biological: Axicabtagene Ciloleucel
A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously following a conditioning chemotherapy regimen of fludarabine and cyclophosphamide
Other Names:
* KTE-C19
* axi-cel
- Drug: Platinum-containing salvage chemotherapy (eg, R-ICE) followed by high dose therapy (eg, BEAM) and autologous stem cell transplant in responders.
Platinum-containing salvage chemotherapy (R-ICE, R-DHAP, R-ESHAP, or R-GDP as selected by treating investigator) followed by high dose therapy (eg, BEAM) and autologous stem cell transplant in responders.
- Drug: Cyclophosphamide
Administered intravenously
- Drug: Fludarabine
Administered intravenously

Phase : III

Stade : NA

Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - Histologically proven DLBCL, including transformation from follicular lymphoma
- Relapsed or refractory disease after first-line chemoimmunotherapy
> Refractory disease is defined as no complete remission to first-line therapy; individuals who are intolerant to first-line therapy are excluded.
*Progressive disease (PD) as best response to first-line therapy
*Stable disease (SD) as best response after at least 4 cycles of first-line therapy
*Partial response (PR) as best response after at least 6 cycles and biopsy-proven residual disease or disease progression ≤ 12 months from initiation of therapy
> Relapsed disease defined as complete remission to first-line therapy followed by biopsy-proven relapse ≤ 12 months of initiating first-line therapy

- Individuals must have received adequate first-line therapy including at a minimum:
> Anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20 negative, and
> An anthracycline containing chemotherapy regimen

- No known history or suspicion of central nervous system involvement by lymphoma
- Eastern cooperative oncology group (ECOG) performance status of 0 or 1
- Adequate bone marrow function as evidenced by:
> Absolute neutrophil count (ANC) ≥ 1000/uL
> Platelet ≥ 75,000/uL
> Absolute lymphocyte count ≥ 100/uL

- Adequate renal, hepatic, cardiac, and pulmonary function as evidenced by:
> Creatinine clearance (Cockcroft Gault) ≥ 60 mL/min
> Serum Alanine aminotransferase/Aspartate aminotransferase (ALT/AST) ≤ 2.5 Upper limit of normal (ULN)
> Total bilirubin ≤ 1.5 mg/dl
> Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an Echocardiogram (ECHO), and no clinically significant Electrocardiogram (ECG) findings
> No clinically significant pleural effusion
> Baseline oxygen saturation > 92% on room air

Critères de non-inclusion : - History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg cervix, bladder, breast) unless disease free for at least 3 years
- Received more than one line of therapy for DLBCL
- History of autologous or allogeneic stem cell transplant
- Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous antimicrobials for management.
- Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive). If there is a positive history of treated hepatitis B or hepatitis C, the viral load must be undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing.
- Individuals with detectable cerebrospinal fluid malignant cells or known brain metastases, or with a history of cerebrospinal fluid malignant cells or brain metastases.
- History or presence of non-malignant central nervous system (CNS) disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
- Presence of any indwelling line or drain. Dedicated central venous access catheter such as a Port-a-Cath or Hickman catheter are permitted.
- History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York Heart Association Class II or greater congestive heart failure, or other clinically significant cardiac diseases within 12 months of enrollment
- History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment
- History of autoimmune disease, requiring systemic immunosuppression and/or systemic disease modifying agents within the last 2 years
- History of anti-CD19 or CAR-T therapy or history of prior randomization in ZUMA-7
Informations relatives au promoteur
Promoteur :
Kite Pharma
Type de sponsor : Industriel

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 : 02/05/2019