Etude : NP 30179 /



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Acronyme
Nom
Traitement
Type d'étude
MÀJ
Présentation de l'étude
Acronyme : NP 30179

Nom :

Traitement :

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 03/05/2019
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : A Multicenter, Open-Label, Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Escalating Doses of RO7082859 as a Single Agent and in Combination With Obinutuzumab, Administered After a Fixed, Single Pre-Treatment Dose of Obinutuzumab (Gazyva®/Gazyvaro™) in Patients With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C85 - Lymphome non hodgkinien, de types autres et non précisés
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : This is a Phase I, multicenter, open-label, dose-escalation study designed to evaluate the efficacy, safety, tolerability and pharmacokinetics (PK) of a novel T-Cell bispecific (TCB), RO7082859, administered by intravenous (IV) infusion as a single agent and in combination with obinutuzumab, following the pre-treatment with a one-time, fixed dose of obinutuzumab. This entry-to-human study is divided in 3 parts: dose escalation (Parts I and II) and dose expansion (Part III). Single-participant dose-escalation cohorts will be used in Part I, followed by conversion to multiple participant dose-escalation cohorts (Part II), in order to define a tentative maximum tolerated dose (MTD) or optimal biological dose (OBD). The expansion cohorts (Part III) will be initiated when the tentative MTD/OBD is defined, to further evaluate the safety, PK and therapeutic activity of RO7082859.

Study Arms:
- Experimental: Part I: Dose Escalation
Participants (single participant cohorts) will receive obinutuzumab (Gpt) 1000 milligrams (mg) single dose IV infusion on Day -7 (pre-treatment) followed by RO7082859 IV infusion on Day 1 and Day 8 of Cycle 1. From Cycle 2 onwards, ascending doses of RO7082859 will be administered on Day 1 of every 2 week cycle up to Cycle 12 (24 weeks) or until unacceptable toxicity or disease progression. RO7082859 dosing will be initiated at 5 micrograms (mcg) (flat dose) followed by doses of 15 mcg, 45 mcg, 135 mcg, 405 mcg and 810 mcg. Tocilizumab will be administered if required, for the management of severe Cytokine Release Syndrome (CRS) (if a study participant experiences severe CRS during or after any infusion of RO7082859).
Interventions:
Drug: RO7082859
Drug: Obinutuzumab
Drug: Tocilizumab

- Experimental: Part II: Dose Escalation
Participants will receive 1000 mg Gpt single dose IV infusion on Day -7 (pre-treatment). Participants (multiple participant cohorts) will start when either RO7082859 flat dose of 810 mcg is reached or a RO7082859-related greater than or equal to (>/=) Grade 2 AE or DLT occurs, whichever comes first. Participants will receive RO7082859 IV infusion on Day 1 of Cycle 1.
Monotherapy, RO7082859 as a single agent: From Cycle 2 onwards, ascending doses of RO7082859 will be administered on Day 1 of every 2 or 3 week cycle until either the MTD/OBD is defined.
Combination Therapy: From Cycle 2 onwards, a fixed dose of 1000 mg Gpt will be administered via IV infusion in combination with ascending doses of RO7082859 on Day 1 of every 3 week cycle until either the MTD/OBD is defined.
Interventions:
Drug: RO7082859
Drug: Obinutuzumab
Drug: Tocilizumab

- Experimental: Part III: Dose Expansion
Part III will start once OBD is defined. Participants will receive Gpt 1000 mg single dose IV infusion on Day -7 (pre-treatment) followed by RO7082859 IV infusion at OBD on Day 1 of Cycle 1.
Monotherapy: From Cycle 2 onwards, RO7082859 will be administered at OBD on Day 1 of every 2 or 3 week cycle up to Cycle 8 (24 weeks) or until unacceptable toxicity or disease progression.
Combination Therapy: From Cycle 2 onwards, a fixed dose of 1000 mg Gpt will be administered via IV infusion in combination with RO7082859 at OBD.
Interventions:
Drug: RO7082859
Drug: Obinutuzumab
Drug: Tocilizumab

Current Primary outcome:
- Part I and II: Percentage of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: From Baseline up to 4 weeks ]
- Part I, II and III: Percentage of Participants With Adverse Events (AEs) [ Time Frame: From Baseline up to 90 days after last dose of study drug or until study completion or participant withdrawal (up to 3 years) ]
- Part II: MTD or OBD of RO7082859 [ Time Frame: From Baseline up to 4 weeks ]
- Part II: Recommended Phase II Dose (RP2D) of RO7082859 [ Time Frame: Baseline up to 3 years ]
- Part I, II and III: Area Under the Serum Concentration Versus Time Curve (AUC) of RO7082859 [ Time Frame: Part I: Cycle 1 Day 1 to Day 8 (pre-dosing of the second infusion). Part II and III: Cycle 1 Day 1 up to Day 71 (pre-infusion of Cycle 6) [detailed time frame is provided in the outcome measure description] ]
- Part I: Pre-dose (Hour [Hr] 0), 2 hrs post-infusion start, end of infusion (EOI) (infusion duration=4 hrs), 0.5, 2, 6, 12 hrs post EOI on Day 1 of Cycle 1; 20, 44, 68, 116 hrs post EOI on Days 2, 3, 4, 6 of Cycle 1 respectively; and pre-dose on Day 8 of Cycle 1 right prior to second infusion Part II and III: Pre-dose (Hr 0), 2 hrs post-infusion start, EOI (infusion duration=4 hrs), 0.5, 2, 6 hrs post EOI on Day 1 of Cycle 2 and Cycle 5; 20, 68, 116, 164, 232 hrs post EOI on Days 2, 4, 6, 8, 11 respectively of Cycles 2 and 5; and pre-dose on Day 1 of Cycles 3 and 6, respectively (Cycle length=14 days)
- Part I, II and III: Maximum Serum Concentration (Cmax) of RO7082859 [ Time Frame: Cycle 1 Day 1 up to 198 days (detailed time is provided in the outcome measure description) ]
- Part I: Pre-dose (Hr 0), 2 hrs post-infusion start, EOI (infusion duration=4 hrs), 0.5, 2, 6, 12 hrs post EOI on Day 1 of Cycle 1; 20, 44, 68, 116 hrs post EOI on Days 2, 3, 4, 6 of Cycle 1 respectively; and pre-dose on Day 8 of Cycle 1 right prior to second infusion Part II and III: Pre-dose (Hr 0), 2 hrs post-infusion start, EOI (infusion duration=4 hrs), 0.5, 2, 6 hrs post EOI on Day 1 of Cycle 2 and Cycle 5; 20, 68, 116, 164, 232 hrs post EOI on Days 2, 4, 6, 8, 11 respectively of Cycles 2 and 5; and pre-dose on Day 1 of Cycles 3 and 6, respectively; EOI on Day 1 of Cycles 3, 4, 6 - 12 (Cycle length=14 days); EOT/early termination visit (up to 198 days)
- Part I, II and III: Minimum Serum Concentration (Cmin) of RO7082859 [ Time Frame: Cycle 1 Day 1 up to 198 days (detailed time is provided in the outcome measure description) ]
- Part I: Pre-dose (Hr 0), 2 hrs post-infusion start, EOI (infusion duration=4 hrs), 0.5, 2, 6, 12 hrs post EOI on Day 1 of Cycle 1; 20, 44, 68, 116 hrs post EOI on Days 2, 3, 4, 6 of Cycle 1 respectively; and pre-dose on Day 8 of Cycle 1 right prior to second infusion Part II and III: Pre-dose (Hr 0), 2 hrs post-infusion start, EOI (infusion duration=4 hrs), 0.5, 2, 6 hrs post EOI on Day 1 of Cycle 2 and Cycle 5; 20, 68, 116, 164, 232 hrs post EOI on Days 2, 4, 6, 8, 11 respectively of Cycles 2 and 5; and pre-dose on Day 1 of Cycles 3 and 6, respectively; EOI on Day 1 of Cycles 3, 4, 6 - 12 (Cycle length=14 days); EOT/early termination visit (up to 198 days)
- Part I, II and III: Clearance (CL) of RO7082859 [ Time Frame: Part I: Cycle 1 Day 1 to Day 8 (pre-dosing of the second infusion). Part II and III: Cycle 1 Day 1 up to Day 71 (pre-infusion of Cycle 6) [detailed time frame is provided in the outcome measure description] ]
- Part I: Pre-dose (Hr 0), 2 hrs post-infusion start, EOI (infusion duration=4 hrs), 0.5, 2, 6, 12 hrs post EOI on Day 1 of Cycle 1; 20, 44, 68, 116 hrs post EOI on Days 2, 3, 4, 6 of Cycle 1 respectively; and pre-dose on Day 8 of Cycle 1 right prior to second infusion Part II and III: Pre-dose (Hr 0), 2 hrs post-infusion start, EOI (infusion duration=4 hrs), 0.5, 2, 6 hrs post EOI on Day 1 of Cycle 2 and Cycle 5; 20, 68, 116, 164, 232 hrs post EOI on Days 2, 4, 6, 8, 11 respectively of Cycles 2 and 5; and pre-dose on Day 1 of Cycles 3 and 6, respectively (Cycle length=14 days)
- Part I, II and III: Volume of Distribution at Steady-State (Vss) of RO7082859 [ Time Frame: Part I: Cycle 1 Day 1 to Day 8 (pre-dosing of the second infusion). Part II and III: Cycle 1 Day 1 up to Day 71 (pre-infusion of Cycle 6) [detailed time frame is provided in the outcome measure description] ]
- Part I: Pre-dose (Hr 0), 2 hrs post-infusion start, EOI (infusion duration=4 hrs), 0.5, 2, 6, 12 hrs post EOI on Day 1 of Cycle 1; 20, 44, 68, 116 hrs post EOI on Days 2, 3, 4, 6 of Cycle 1 respectively; and pre-dose on Day 8 of Cycle 1 right prior to second infusion Part II and III: Pre-dose (Hr 0), 2 hrs post-infusion start, EOI (infusion duration=4 hrs), 0.5, 2, 6 hrs post EOI on Day 1 of Cycle 2 and Cycle 5; 20, 68, 116, 164, 232 hrs post EOI on Days 2, 4, 6, 8, 11 respectively of Cycles 2 and 5; and pre-dose on Day 1 of Cycles 3 and 6, respectively (Cycle length=14 days)
- Part I, II and III: Half-Life (t1/2) of RO7082859 [ Time Frame: Part I: Cycle 1 Day 1 to Day 8 (pre-dosing of the second infusion). Part II and III: Cycle 1 Day 1 up to Day 71 (pre-infusion of Cycle 6) [detailed time frame is provided in the outcome measure description] ]
- Part I: Pre-dose (Hr 0), 2 hrs post-infusion start, EOI (infusion duration=4 hrs), 0.5, 2, 6, 12 hrs post EOI on Day 1 of Cycle 1; 20, 44, 68, 116 hrs post EOI on Days 2, 3, 4, 6 of Cycle 1 respectively; and pre-dose on Day 8 of Cycle 1 right prior to second infusion Part II and III: Pre-dose (Hr 0), 2 hrs post-infusion start, EOI (infusion duration=4 hrs), 0.5, 2, 6 hrs post EOI on Day 1 of Cycle 2 and Cycle 5; 20, 68, 116, 164, 232 hrs post EOI on Days 2, 4, 6, 8, 11 respectively of Cycles 2 and 5; and pre-dose on Day 1 of Cycles 3 and 6, respectively (Cycle length=14 days)

Secondary outcomes:
- Part I, II and III: Cmax of Obinutuzumab [ Time Frame: Pre-dose of obinutuzumab on Day -7; pre-dose (Hr 0) of RO7082859 on Day 1 of Cycle 1 (Cycle length=14 days) ]
- Part I, II and III: Cmin of Obinutuzumab [ Time Frame: Pre-dose of obinutuzumab on Day -7; pre-dose (Hr 0) of RO7082859 on Day 1 of Cycle 1 (Cycle length=14 days) ]
- Part I, II and III: Anti-Drug Antibodies (ADA) to RO7082859 [ Time Frame: Pre-dose of obinutuzumab on Day -7; pre-dose (Hr 0) of RO7082859 on Day 8 of Cycle 1, Day 1 of Cycles 2-12 (Cycle length=14 days); EOT/follow-up visit (up to 3 years) ]
- Part I, II and III: Percentage of Participants With Overall Response (Partial Response [PR] or Complete Response [CR]) as Determined by the Modified Lugano Classification [ Time Frame: From Baseline up to end of study or discontinuation due to disease progression (up to 3 years) ]
- Part I, II and III: Percentage of Participants With Stable disease (SD) as Determined by the Modified Lugano Classification [ Time Frame: From Baseline up to end of study or discontinuation due to disease progression (up to 3 years) ]
- Part I, II and III: Percentage of Participants With PR, CR or SD (Disease Control Rate) as Determined by the Modified Lugano Classification [ Time Frame: From Baseline up to end of study or discontinuation due to disease progression (up to 3 years) ]
- Part I, II and III: Duration of Response (DOR) as Determined by the Modified Lugano Classification [ Time Frame: From first occurrence of documented objective response until disease progression, relapse or death due to any cause (up to 3 years) ]
- Part I, II and III: Duration of Complete Response (DOCR) as Determined by the Modified Lugano Classification [ Time Frame: From the first occurrence of a documented, complete response, until the time of relapse or death from any cause (up to 3 years) ]
- Part I, II and III: Progression-Free Survival (PFS) as Determined by the Modified Lugano Classification [ Time Frame: From first study treatment to the first occurrence of disease progression or death due to any cause (up to 3 years) ]
- Overall Survival (OS) [ Time Frame: From the time of first study treatment to death from any cause (up to 3 years) ]
- Health Related Quality of Life (HRQoL) as Assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) [ Time Frame: From baseline through follow-up or until disease progression (up to 3 years) ]
- HRQoL as Assessed by the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Scale [ Time Frame: From baseline through follow-up or until disease progression (up to 3 years) ]

Phase : I

Stade : NA

2, 3, 4, X
Critères d'inclusion
Critères de non-inclusion
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - Depending upon study part, a history or status of: 1) a histologically-confirmed hematological malignancy that is expected to express cluster of differentiation (CD)20; 2) relapse after or failure to respond to at least one prior treatment regimen; and 3) no available treatment options that are expected to prolong survival (e.g., standard chemotherapy or autologous stem cell transplant [SCT])
- Participant must have at least one measureable target lesion (>/=1.5 centimeters [cm]) in its largest dimension by computerized tomography [CT] scan)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Life expectancy of >/=12 weeks
- AEs from prior anti-cancer therapy must have resolved to Grade less than or equal to (=) 1
- Adequate liver, hematological and renal function
- Negative serologic or polymerase chain reaction (PCR) test results for acute or chronic Hepatitis B virus (HBV) infection
- Negative test results for Hepatitis C virus (HCV) and human immunodeficiency virus (HIV)

Critères de non-inclusion : - Participants with chronic lymphocytic leukemia (CLL), Burkitt lymphoma and lymphoplasmacytic lymphoma
- Participants with acute bacterial, viral, or fungal infection at baseline, confirmed by a positive blood culture within 72 hours prior to obinutuzumab infusion or by clinical judgment in the absence of a positive blood culture
- Participants with known active infection, or reactivation of a latent infection, whether bacterial, viral, fungal, mycobacterial, or other pathogens or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of dosing
- Prior treatment with systemic immunotherapeutic agents, including, but not limited to, radio-immunoconjugates, antibody-drug conjugates, immune/cytokines and monoclonal antibodies (e.g., anti-cytotoxic T-lymphocyte-associated protein 4 [anti-CTLA4], anti-programmed death 1 [anti-PD1] and anti-programmed death ligand 1 [anti-PDL1]) within 4 weeks or five half-lives of the drug, whichever is shorter, before obinutuzumab infusion on Cycle 1 Day -7
- History of treatment-emergent immune-related AEs associated with prior immunotherapeutic agents
- Documented refractoriness to an obinutuzumab-containing regimen
- Treatment with standard radiotherapy, any chemotherapeutic agent, or treatment with any other investigational anti-cancer agent within 4 weeks prior to obinutuzumab infusion
- Prior solid organ transplantation
- Prior allogeneic SCT
- Autologous SCT within 100 days prior to obinutuzumab infusion
- Participant with history of confirmed progressive multifocal leukoencephalopathy (PML)
- Current or past history of central nervous system (CNS) lymphoma
- Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders and known autoimmune diseases
- Participants with another invasive malignancy in the last 2 years (with the exception of basal cell carcinoma and tumors deemed by the Investigator to be of low likelihood for recurrence)
- Administration of a live, attenuated vaccine within 4 weeks before obinutuzumab infusion or anticipation that such a live attenuated vaccine will be required during the study
- Received systemic immunosuppressive medications (including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) with the exception of corticosteroid treatment =25 mg/day prednisone or equivalent within 2 weeks prior to obinutuzumab infusion
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT03075696
Promoteur :
HOFFMANN-LA ROCHE
Type de sponsor : Industriel
00000 HORS FRANCE

Coordonnateur :
global-roche-genentech-trials@gene.com
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre Hospitalier Universitaire de Lille - 2 Avenue Oscar Lambret - 59000 LILLE

Investigateur :
Professeur Franck MORSCHHAUSER

TEC / ARC / IDE :
Secrétariat de recherche
fanny.miquel@
chru-lille.fr
03.20.44.57.13

Ouverture de l'essai : OUVERT

MAJ : 03/05/2019