- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT01939899
Phase 2 Study of Oral IXAZOMIB in Adult Participants With Relapsed and/or Refractory Follicular Lymphoma
7 octobre 2019 mis à jour par: Millennium Pharmaceuticals, Inc.
An Open-label, Multicenter, Phase 2 Study of Oral IXAZOMIB (MLN9708) in Adult Patients With Relapsed and/or Refractory Follicular Lymphoma
The primary purpose of this study is to evaluate the anti-tumor activity of oral Ixazomib as measured by overall response rate (ORR) in adult participants with relapsed and/or refractory follicular lymphoma (FL).
Aperçu de l'étude
Type d'étude
Interventionnel
Inscription (Réel)
29
Phase
- Phase 2
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
-
-
-
Gent, Belgique
-
Leuven, Belgique
-
Wilrijk, Belgique
-
-
-
-
Quebec
-
Montreal, Quebec, Canada
-
-
-
-
-
London, Royaume-Uni
-
Manchester, Royaume-Uni
-
Newcastle Upon Tyne, Royaume-Uni
-
Plymouth, Royaume-Uni
-
Southampton, Royaume-Uni
-
Sutton, Royaume-Uni
-
-
-
-
Massachusetts
-
Boston, Massachusetts, États-Unis
-
-
New York
-
New York, New York, États-Unis
-
-
Tennessee
-
Nashville, Tennessee, États-Unis
-
-
Texas
-
Houston, Texas, États-Unis
-
-
Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
Inclusion Criteria:
- Male or female participants 18 years or older.
- Participants must have a pathologically confirmed diagnosis of non-Hodgkin lymphoma (NHL) (for the lead-in dose-finding phase) and FL (for phase 2).
- Participants must have radiographically or clinically measurable disease.
- Participants must be relapsed and/or refractory after at least 1 prior therapy (excluding radiation) with documented progressive disease at the time of enrollment.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to practice true abstinence.
- Male participants who agree to practice effective barrier contraception or agree to practice true abstinence.
- Voluntary written consent.
- Suitable venous access.
- Appropriate clinical laboratory values as defined in the protocol.
- Recovered from toxicities of prior anticancer therapy.
- If the trial proceeds to the second step on the basis of the tandem 2-step design, participants must be confirmed PSMB1 positive at the central laboratory before treatment.
Exclusion Criteria
- Peripheral neuropathy that is greater or equal to Grade 2 or Grade 1 with pain.
- Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period.
- Autologous stem cell transplant within 6 months before Day 1 of Cycle 1, or prior allogeneic stem cell transplant at any time.
- Major surgery within 14 days before the first dose of study drug.
- Infection requiring systemic antibiotic therapy or other serious infection within 14 days before the first dose of study drug.
- Comorbid systemic illnesses or other severe concurrent disease that, in the judgment of the investigator, would make the participants inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
- Evidence of current uncontrolled cardiovascular conditions including uncontrolled hypertension, severe uncontrolled ventricular arrhythmias, unstable angina, New York Heart Association (NYHA) Class III or IV cardiac disease, or myocardial infarction within the past 6 months.
- Diarrhea greater than (>) Grade 1 on the basis of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) categorization.
- Systemic antineoplastic (including glucocorticoids > the equivalent of 15 mg of prednisone daily), experimental, or radiation therapy within 21 days before the first dose of study drug.
- Prior treatment with rituximab or other unconjugated antibody treatment within 42 days (21 days if clear evidence of progressive disease or immediate treatment is mandated).
- Treatment with radioimmunoconjugates or toxin immunoconjugates within 12 weeks before the first dosing of study treatment.
- Systemic treatment with strong inhibitors of Cytochrome P450 1A2 (CYP1A2) or Cytochrome P450 3A (CYP3A), or strong CYP3A inducers within 14 days before the first dose of IXAZOMIB - Ongoing systemic therapy with corticosteroids.
- Central nervous system (CNS) involvement that is clinically uncontrolled or newly diagnosed in the last 4 months.
- Ongoing or active systemic viral infection, known human immunodeficiency virus (HIV) positive, known active hepatitis B virus or known active hepatitis C virus.
- Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease with the exception of nonmelanoma skin cancer or any completely resected carcinoma in situ.
- Platelet transfusions within 3 days before the 1st dose of study drug.
- Inability to swallow capsules, or inability or unwillingness to avoid taking anything by mouth except for water and prescribed medication for 2 hours before and 1 hour after dose of IXAZOMIB - Known allergy to boron or excipients in the formulation.
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: IXAZOMIB
Ixazomib 4, 5.3 and 7 milligram (mg), orally, once on Days 1, 8 and 15 in a 28 day treatment cycle followed by a rest period of 13 days, for up to Cycle 29 or until disease progression or unacceptable toxicity at lead-in phase for participants with NHL.
After completion of lead-in phase, participants will continue into Phase 2. Participants in Phase 2 will receive Ixazomib at RP2D dose, orally, once weekly on Days 1, 8 and 15 in a 28 day treatment cycle followed by a rest period of 13 days , for up to Cycle 29 or until disease progression or unacceptable toxicity in Phase 2 for participants with RRFL.
|
Each 28-day treatment cycle will include oral administration of IXAZOMIB on Days 1, 8, and 15 followed by a rest period of 13 days.
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Number of Participants With Overall Response Rate (ORR)
Délai: Baseline up to Day 15 Cycle 29 (approximately up to Day 802) or until PD or the start of alternate therapies
|
ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by the investigator using the international Working Group criteria for participants CR: disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level.
PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions.
|
Baseline up to Day 15 Cycle 29 (approximately up to Day 802) or until PD or the start of alternate therapies
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Lead-in Dose Finding Phase: Recommended Phase 2 Dose (RP2D)
Délai: Baseline up to Cycle 1 Day 28
|
Baseline up to Cycle 1 Day 28
|
|
|
Progression Free Survival (PFS)
Délai: Time from the date of first dose of study treatment to the date of first documented PD or death (approximately up to Day 802)
|
PFS is defined as the time from the date of first dose of study treatment to the date of first documented PD or death.
Participants without documentation of PD will be censored at the date of last response assessment that is SD or better.
Participants without response assessment will be censored at the date of first dose.
|
Time from the date of first dose of study treatment to the date of first documented PD or death (approximately up to Day 802)
|
|
Phase 2: Rate of Disease Control
Délai: Baseline or until occurrence of disease progression, unacceptable toxicities, or discontinuation of study due to any other reasons (approximately up to Day 805)
|
Rate of disease control is defined as percentage of participants who achieved a SD or better for greater than or equal to (>=) 6 months.
|
Baseline or until occurrence of disease progression, unacceptable toxicities, or discontinuation of study due to any other reasons (approximately up to Day 805)
|
|
Time to Response (TTR)
Délai: Time from the date of first dose of study treatment to the date of first documented PR or better response or death (approximately up to Day 802)
|
TTR is defined as the time from the date of first dose of study treatment to the date of the first documentation of a PR or better response in a participant who responded.
|
Time from the date of first dose of study treatment to the date of first documented PR or better response or death (approximately up to Day 802)
|
|
Duration of Response (DOR)
Délai: Time from the date of first documentation of a response to the date of first documented PD (approximately up to Day 802)
|
The DOR is defined as the time from the date of first documentation of a response to the date of first documented PD.
Responders without documentation of PD will be censored at the date of last response assessment.
DOR was categorized as CR+PR and CR.
|
Time from the date of first documentation of a response to the date of first documented PD (approximately up to Day 802)
|
|
Phase 2: Number of Participants With Response Rates in PSMB1 Positive and PSMB1 Negative
Délai: Baseline up to occurrence of disease progression, unacceptable toxicities, or discontinuation of study due to any other reasons (approximately up to Day 802)
|
Baseline up to occurrence of disease progression, unacceptable toxicities, or discontinuation of study due to any other reasons (approximately up to Day 802)
|
|
|
Number of Participants Experiencing 1 or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Délai: Baseline up to 30 days after last dose of study drug (approximately up to Day 832)
|
Baseline up to 30 days after last dose of study drug (approximately up to Day 832)
|
|
|
Lead-in Dose Finding Phase: Cmax: Maximum Observed Plasma Concentration for Ixazomib
Délai: Cycle 1, Days 1 and 15 pre-dose and at multiple time points (up to 168 hours) post-dose
|
Cycle 1, Days 1 and 15 pre-dose and at multiple time points (up to 168 hours) post-dose
|
|
|
Lead-in Dose Finding Phase: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
Délai: Cycle 1, Days 1 and 15 pre-dose and at multiple time points (up to 168 hours) post-dose
|
Cycle 1, Days 1 and 15 pre-dose and at multiple time points (up to 168 hours) post-dose
|
|
|
Lead-in Dose Finding Phase: AUC(0-168): Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Postdose for Ixazomib
Délai: Cycle 1, Days 1 and 15 pre-dose and at multiple time points (up to 168 hours) post-dose
|
Cycle 1, Days 1 and 15 pre-dose and at multiple time points (up to 168 hours) post-dose
|
Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude (Réel)
31 octobre 2013
Achèvement primaire (Réel)
1 juin 2016
Achèvement de l'étude (Réel)
23 mars 2017
Dates d'inscription aux études
Première soumission
28 août 2013
Première soumission répondant aux critères de contrôle qualité
6 septembre 2013
Première publication (Estimation)
11 septembre 2013
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
29 octobre 2019
Dernière mise à jour soumise répondant aux critères de contrôle qualité
7 octobre 2019
Dernière vérification
1 octobre 2019
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Maladies du système immunitaire
- Tumeurs par type histologique
- Tumeurs
- Troubles lymphoprolifératifs
- Maladies lymphatiques
- Troubles immunoprolifératifs
- Lymphome non hodgkinien
- Lymphome
- Lymphome folliculaire
- Mécanismes moléculaires de l'action pharmacologique
- Inhibiteurs d'enzymes
- Agents antinéoplasiques
- Inhibiteurs de protéase
- Ixazomib
Autres numéros d'identification d'étude
- C16017
- 2013-002302-32 (Numéro EudraCT)
- U1111-1164-7551 (Autre identifiant: WHO)
- 166547 (Identificateur de registre: HC-CTD)
- REec-2016-2137 (Identificateur de registre: REec)
- 13/EM/0373 (Identificateur de registre: NRES)
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .