Etude : C16029 / Millenium C16029



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Acronyme
Nom
Traitement
Type d'étude
MÀJ
Présentation de l'étude
Acronyme : C16029

Nom : Millenium C16029

Traitement :

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 12/11/2019
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : Étude de Phase 2/3, randomisée, en ouvert, comparant l’Ixazomib/la Dexaméthasone par voie orale et le Pomalidomide/la Dexaméthasone par voie orale dans le myélome multiple en rechute et/ou réfractaire

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C90 - Myélome multiple et tumeurs malignes à plasmocytes
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : The drug being tested in this study is called Ixazomib. Ixazomib is being tested to treat people who have RRMM. This study will compare the efficacy and safety in participants who take ixazomib and dexamethasone to pomalidomide and dexamethasone. It is an open-label, phase 2 study that, on the basis of a prespecified go/no-go decision rule, will progress to a phase 3 registrational study.

The study will enroll approximately 300 patients. Participants will receive:
- Ixazomib 4 mg + dexamethasone 20 mg (or 10 mg if participant is aged >=75 years) OR
- pomalidomide 4 mg + dexamethasone 40 mg (or 20 mg if participant is aged >=75 years)

All participants will be asked to take either ixazomib plus dexamethasone (in cases where only 4 mg tablets for dexamethasone are available, the following dexamethasone schedule is recommended for participants aged >=75 years: 12 mg dexamethasone will be given on Days 1, 8, 15, and 22 of every 28-day cycle; and 8 mg dexamethasone will be given on Days 2, 9, 16, and 23 of every 28-day cycle) or pomalidomide 4 mg + dexamethasone 40 mg at recommended doses.

This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 63 months if the phase 3 portion of the study is completed. Alternatively, if the no-go criteria are met during the phase 2 portion, the study will be completed approximately 22 to 29 months after the first participant enters the study.

Participants will make multiple visits to the clinic, and will be contacted for PFS follow-up, in case of study drug discontinuation for up to 7 years from first dose administration. After disease progression, participants will be followed-up for OS every 12 weeks until death or up to 10 years.


Study arms:
- Experimental: Ixazomib plus dexamethasone
Ixazomib 4 mg as starting dose, capsules, orally on Days 1, 8, and 15 of each 28-day cycle, with escalation to 5.5 mg at Cycle 2 for participants who tolerate the 4 mg dose in Cycle 1, plus dexamethasone 20 mg (or 10 mg if participant is aged >=75 years) tablets, orally, on Days 1, 2, 8, 9, 15, 16, 22, and 23 of every 28-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or sponsor termination of study (up to 63 months).

- Active Comparator: Pomalidomide plus dexamethasone
Pomalidomide 4 mg, capsules, orally on Days 1 to 21 of each 28-day cycle plus dexamethasone 40 mg, (or 20 mg if participant is aged >=75 years), tablets, orally on Days 1, 8, 15, and 22 of each 28-day cycle until disease progression, unacceptable toxicity, withdrawal of consent, or sponsor termination of study (up to 63 months).


Current primary outcome:
Progression Free Survival (PFS) [ Time Frame: From date of randomization until disease progression or death due to any cause, whichever occurs first (Up to 7 years) ]

Current secondary outcomes:
- Overall Survival (OS) [ Time Frame: From randomization to death from any cause (Up to 10 years) ]
- Percentage of Participants with Objective Response Rate (ORR - Partial Response [PR], Very Good Partial Response [VGPR] and Complete Response [CR]) [ Time Frame: Day 1 of Cycle 1 (28 day cycle) then every cycle until disease progression for up to 7 years ]
- Duration of Response (DOR) [ Time Frame: Day 1 of Cycle 1 (28 day cycle) then every cycle until disease progression for up to 7 years ]
- Time to Response [ Time Frame: Day 1 of Cycle 1 (28 day cycle) then every cycle until the first documentation of PR or PR/VGPR/CR for up to 7 years ]
- Time to Progression (TTP) [ Time Frame: Day 1 of Cycle 1 (28 day cycle) then every cycle until disease progression for up to 7 years ]
- Health-Related Quality of Life (HRQOL) based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire- Core 30 (EORTC QLQ-C30) Physical Domain Score [ Time Frame: Baseline up to 7 years ]
- HRQOL based on EORTC QLQ-C30 Total Score [ Time Frame: Baseline up to 7 years ]
- HRQOL based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score [ Time Frame: Baseline up to 7 years ]
- HRQOL based on 5-level Classification System of the EuroQol 5-Dimensional Health Questionnaire (EQ-5D-5L) Score [ Time Frame: Baseline up to 7 years ]
- Health Care Utilization (HU): Number of Medical Encounters [ Time Frame: Baseline up to 7 years ]
- HU: Duration of Medical Encounters [ Time Frame: Baseline up to 7 years ]

Phase : II/III

Stade : NA

4
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 : - Must have a confirmed diagnosis of multiple myeloma (MM) requiring therapy according to IMWG criteria.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- Must have had a relapse or PD after having received 2 or more prior lines of systemic therapy. Note: A line of therapy is defined as 1 or more cycles of a planned treatment program; this may consist of 1 or more planned cycles of single-agent therapy or combination therapy, as well as a sequence of treatments administered in a planned manner. For example, a planned treatment approach of induction therapy followed by autologous SCT, followed by maintenance is considered 1 line of therapy. Typically each line of therapy is separated by PD. Discussion with the medical monitor may help clarify the number of lines of therapy that a prospective study participant had.
- Must be refractory to lenalidomide, defined as having received at least 2 consecutive cycles of lenalidomide as a single agent or within a lenalidomide-containing regimen and having had PD during treatment with or within 60 days after the last dose of lenalidomide. The starting dose of lenalidomide should have been 25 mg (or as low as 10 mg in the case of renal function impairment or other safety concern), and the final dose should have been a minimum of 10 mg.
- Must have received at least 2 consecutive cycles of a bortezomib- or carfilzomib-containing regimen, and either:
* Achieved at least a PR and did not have PD during treatment with or within 60 days after the last dose of bortezomib or carfilzomib, OR
* Had bortezomib and/or carfilzomib intolerance (defined as discontinuation because of drug-related adverse events [AEs] before completion of the planned treatment course) without PD before the start of the next regimen.
- Must have measurable disease defined by:
* Serum M-protein >=1 g/dL (>=10 g/L), OR
* Urine M-protein >=200 mg/24 hours and must have documented MM isotype by immunofixation (central laboratory).
- Suitable venous access for the study-required blood sampling, including pharmacokinetic (PK) sampling.
- Recovered (that is, less than or equal to [<=] Grade 1 nonhematologic toxicity) from the reversible effects of prior anticancer therapy.
- Must be willing and able to adhere to pomalidomide-related risk mitigation activities if randomized to the pom+dex arm (example, Risk Evaluation and Mitigation Strategies [REMS], pregnancy prevention programs).

Critères de non-inclusion : - Prior allogenic bone marrow transplantation in any prior line of therapy or prior autologous SCT in the last prior line of therapy- unless the autologous SCT was performed a year or more before disease progression.
- Diagnosed with or treated for another malignancy within 2 years before randomization, or previously diagnosed with another malignancy and have any evidence of residual, persistent, or recurrent disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
- Diagnosis of smoldering MM, Waldenström's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
- Peripheral neuropathy Grade 1 with pain or Grade 2 or higher peripheral neuropathy of any cause on clinical examination during the Screening period.
- Treatment with any investigational products or with chimeric or fully human monoclonal antibodies within 30 days before randomization, systemic anticancer therapy or radiotherapy within 14 days before randomization (Note: "spot" radiation for areas of pain is permitted), and major surgery within 14 days before randomization.
- Known gastrointestinal disease or gastrointestinal procedure that could interfere with the oral absorption or tolerance of study therapy, including difficulty swallowing.
- Serious infection requiring parenteral antibiotic therapy or any other serious infection within 14 days before randomization.
- Central nervous system involvement with MM (by clinical symptoms and signs).
- Ongoing or active systemic infection, known human immunodeficiency virus-ribonucleic acid (RNA) positive, known hepatitis B surface antigen seropositive, or known hepatitis C virus-RNA positive.
- Systemic treatment with strong cytochrome P-450 3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital) or use of St. John's wort within 14 days before randomization.
- Admission or evidence of illicit drug use, drug abuse, or alcohol abuse.
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT03170882
Promoteur :
MILLENIUM PHARMACEUTICALS
Type de sponsor : Industriel
MILLENIUM PHARMACEUTICALS - MILLENIUM PHARMACEUTICALS
00000 HORS FRANCE

Coordonnateur :
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre hospitalier de Dunkerque - 130, avenue Louis Herbeaux - CS 76367 - 59140 DUNKERQUE

Investigateur :
Docteur Hélène DEMARQUETTE

TEC / ARC / IDE :
Virginie EL AZOUZI - PAQUEZ
Virginie.Paquez@
ch-dunkerque.fr
03 28 28 59 00 poste 6485

Ouverture de l'essai : OUVERT

MAJ : 12/11/2019