Etude : LYM3003 /



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Acronyme
Nom
Traitement
Type d'étude
MÀJ
Présentation de l'étude
Acronyme : LYM3003

Nom :

Traitement :

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 25/11/2019
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : Étude randomisée, en ouvert, évaluant la tolérance et l'efficacité de l'ibrutinib chez des enfants et de jeunes adultes atteints d'un lymphome non hodgkinien à cellules B matures en rechute ou réfractaire

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 : The purpose of this study is to confirm that the pharmacokinetics of ibrutinib in pediatric participants is consistent with that in adults (part 1) and to assess efficacy (event-free survival [EFS]) of ibrutinib in combination with rituximab, ifosfamide, carboplatin, and etoposide (RICE) or rituximab, vincristine, ifosfamide, carboplatin, and idarubicin (RVICI) background therapy compared to RICE or RVICI background therapy alone (part 2).


Study arms:
- Experimental: Part 1: Ibrutinib
The first 2 participants enrolled in each age group (1-5 years, 6-11 years and 12-17 years) will receive starting dose of Ibrutinib 240 milligram per square meter (mg/m^2) for the first cycle, followed by dose escalation at the start of Cycle 2 as long as all pharmacokinetic assessments are within the expected range and there are no safety concerns. For participants being treated at 240 mg/m^2 dose level during the first cycle, the maximum dose should not exceed a total of 420 mg/day. All participants will receive rituximab, ifosfamide, carboplatin, etoposide and dexamethasone (RICE) or ituximab, vincristine, ifosfamide, carboplatin, idarubicin and dexamethasone (RVICI) background therapy (investigator's choice), during treatment phase. Participants with PR or better only will receive Ibrutinib for 3 cycles or until PD, unacceptable toxicity or until initiating antilymphoma therapy or a conditioning regimen for stem cell transplantation during post-treatment phase.

- Experimental: Part 2: Ibrutinib
Participants will either receive ibrutinib and RICE/RVICI background therapy or RICE/RVICI background therapy alone, until 3 cycles are completed or until PD or unacceptable toxicity during the treatment phase. Participants who received ibrutinib and RICE/RVICI background therapy and with PR or better only will receive ibrutinib alone for 3 cycles during post-treatment phase.


Current primary outcome:
Part 1:
- Area Under The Plasma Concentration-Time Curve (AUC) of Ibrutinib [ Time Frame: Predose, at 1, 2, 4, and 6 hours postdose on Day 1, and Day 7 or 8 of cycle 1; predose, 1, 2, 4, and 6 hours postdose on Day 1 of Cycle 2 or Cycle 3 (each cycle of 28 days) ]
- Apparent (oral) Plasma Clearance (CL/F) of Ibrutinib [ Time Frame: Predose, at 1, 2, 4, and 6 hours postdose on Day 1, and Day 7 or 8 of Cycle 1; predose, 1, 2, 4, and 6 hours postdose on Day 1 of Cycle 2 or Cycle 3 (each cycle of 28 days) ]
- Apparent (oral) Volume of Distribution (Vd/F) of Ibrutinib [ Time Frame: Predose, at 1, 2, 4, and 6 hours postdose on Day 1, and Day 7 or 8 of cycle 1; predose, 1, 2, 4, and 6 hours postdose on Day 1 of Cycle 2 or Cycle 3 (each cycle of 28 days) ]
- Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Predose, at 1, 2, 4, and 6 hours postdose on Day 1, and Day 7 or 8 of cycle 1; predose, 1, 2, 4, and 6 hours postdose on Day 1 of Cycle 2 or Cycle 3 (each cycle of 28 days) ]
- Relationship Between Pharmacokinetic Parameters and Age or Measure of Body Size [ Time Frame: up to three 28-day cycles ]

Part 2: Event-free Survival [EFS]) of Ibrutinib [ Time Frame: Randomization to death, disease progression, or lack of CR or PR after 3 cycles of treatment (approximately 4.2 years) ]

Current secondary outcomes:
Part 1:
- Number of Participants with Adverse Events [ Time Frame: Throughout the study duration (approximately up to 4.2 years) ]
- Percentage of Participants Who Achieve Complete Response (CR) and Partial Response (PR) [ Time Frame: Approximately up to 4.2 years ]
- Disease-specific Biomarkers Assessment [ Time Frame: Cycle 1: Days 1, and 7 or 8, Cycle 2: Day 1, and Cycle 3: Day 1 (each cycle of 28 days) and End of treatment visit (30 days after last dose) ]
- Bruton's tyrosine kinase (BTK) Percent Occupancy [ Time Frame: Predose and 4 hours postdose on Day 1, Day 7 or 8 of Cycle 1, predose on Cycle 2 Day 1 or Cycle 3 Day 1 (each cycle of 28 days), and the End-of-Treatment visit (30 days after last dose) ]
- Visual analog Scale Score for Palatability [ Time Frame: Cycle 1 Day 1 and Cycle 3 Day 1 (each cycle of 28 days) ]

Part 2:
- Number of Participants with Adverse Events [ Time Frame: Throughout the study duration (approximately up to 4.2 years) ]
- Percentage of Participants Who Achieve Complete Response (CR) and Partial Response (PR) [ Time Frame: Approximately up to 4.2 years ]
- Tumor Volume Reduction [ Time Frame: Day 14 ]
- Percentage of Participants who Proceed to Stem Cell Transplantation [ Time Frame: Cycle 2 (Day 28) ]
- Time to Response [ Time Frame: Up to 4.2 years ]
- Duration of Response [ Time Frame: Up to 4.2 years ]
- Percentage of Participants with Long-term Survival [ Time Frame: 2, 3 years ]
- Overall Survival [ Time Frame: Randomization to the date of death (maximum up to 4.2 years) ]
- Disease-specific Biomarkers Assessment [ Time Frame: Cycle 1: Days 1 and 14, Cycle 2: Day 1, Cycle 3: Day 1 (each cycle of 28 days) and End of treatment visit (30 days after last dose) ]
- Bruton's tyrosine kinase (BTK) Percent Occupancy [ Time Frame: Predose and 4 hours postdose on Cycle 1 Day 1, predose and 4 hours post dose on Cycle 1 Day 14 or Cycle 2 Day 1, predose on Cycle 3 Day 1 (each cycle of 28 days), and End-of-Treatment visit (30 days after last dose) ]
- Visual analog Scale Score for Palatability [ Time Frame: Cycle 1 Day 1 and Cycle 3 Day 1 (each cycle of 28 days) ]
- Area under the plasma concentration-time curve (AUC) [ Time Frame: Predose, 1, 2, and 4 hours postdose, either on Cycle 1 Day 14 or Cycle 2 Day 1 (each cycle of 28 days) ]

Phase : III

Stade : NA

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 : - Participants with 1 to less than (<) 18 years of age (Part 1 only), or 1 to 30 years of age, inclusive, if initial diagnosis of mature B-cell non-Hodgkin lymphoma (NHL) occurred at <18 years of age (Part 2 only)
- Participants must be in first recurrence or have disease that is primarily refractory to conventional therapy
- Participants must have at least 1 of the following: 1 site of measurable disease greater than (>) 1 centimeter (cm) in the longest diameter and >1 cm in the shortest diameter by radiological imaging; bone marrow involvement; cerebrospinal fluid with blasts present
- Participants with lansky-Karnofsky score of greater than or equal to (>=) 50
- Adolescent women/young women of childbearing potential must have a negative highly sensitive serum or urine beta-human chorionic gonadotropin (beta-hCG) pregnancy test at Screening before enrollment/randomization. Adolescent/young women who are pregnant or breastfeeding are ineligible for this study

Critères de non-inclusion : - Participants with ongoing anticoagulation treatment with warfarin or equivalent vitamin K antagonists (example phenprocoumon), or ongoing treatment with agents known to be strong CYP3A4/5 inhibitors, or has taken any disallowed therapies as noted in Section 8.2, Prohibited Medications, before the planned first dose of study drug
- Participants with inherited or acquired bleeding disorders
- Participants with clinically significant arrhythmias, complex congenital heart disease, or left ventricular ejection fraction (LVEF) <50 percent (%) or shortening fraction (SF) <=28%
- Participants with known history of human immunodeficiency virus (HIV) or active Hepatitis B or C virus
- Participants with any condition that could interfere with the absorption or metabolism of ibrutinib including malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel
- Participants with known allergies, hypersensitivity, or intolerance to ibrutinib or its excipients (refer to Investigator's Brochure)
- A diagnosis of post-transplant lymphoproliferative disease (PTLD)
- Participants who are within 6 months of an allogeneic bone marrow transplant
- Participants who have had prior exposure to ibrutinib
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT02703272
Promoteur :
JANSSEN
Type de sponsor : Industriel
JANSSEN - JANSSEN
00000 HORS FRANCE

Coordonnateur :
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 :
Docteur Brigitte NELKEN

TEC / ARC / IDE :
Amandine GORALSKI
amandine.goralski@
chru-lille.fr
03.20.44.60.58

Ouverture de l'essai : OUVERT

MAJ : 25/11/2019