Etude : RRMM / C16047



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

Nom : C16047

Traitement : Induction

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 28/01/2020
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : A Phase 2, Open-Label Study of Ixazomib+Daratumumab+Dexamethasone (IDd) in Relapsed and/or Refractory Multiple Myeloma (RRMM)

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C90 - Myélome multiple et tumeurs malignes à plasmocytes
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : The regimen being tested in this study is the combination of ixazomib, daratumumab, and dexamethasone. This study will look at the efficacy and safety of Ixazomib + Daratumumab + Dexamethasone (IDd) in people who have relapsed and/or refractory multiple myeloma (RRMM).

The study will enroll approximately 60 patients. Participants will be assigned to the treatment group:

• Ixazomib 4.0 mg + Daratumumab 16.0 mg/kg + Dexamethasone 20 mg
All participants will be asked to take Ixazomib on Days 1, 8 and 15 of each 28-day cycle plus Daratumumab on Days 1, 8, 15 and 22 of each 28-day cycle for Cycles 1 and 2, on Days 1 and 15 of each 28-day cycle for Cycles 3 through 6 and on Day 1 of each 28-day cycle for Cycle 7 and beyond plus Dexamethasone orally on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day cycle.

This multi-center trial will be conducted worldwide. The overall time to participate in this study is 5 years. Participants will make multiple visits to the clinic, and every 12 weeks after PD until death or termination of the study by the sponsor.

Current primary outcome:
Percentage of Participants With Very Good Partial Response (VGPR) or Better [ Time Frame: Up to 3 years ]
Response will be assessed using International Myeloma Working Group (IMWG) Criteria. VGPR is defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours.

Current secondary outcomes:
- Progression-free Survival (PFS) [ Time Frame: Up to 5 years ]
PFS is defined as time from date of first dose of drug to date of first documentation of progressive disease (PD) or death from any cause, whichever occurs first. PD: Increase of 25% from lowest response value in any of following: Serum M component with increase ≥ 0.5 gm/dL; serum M component increases ≥1 gm/dL are sufficient to define relapse if starting M component is ≥ 5 gm/dL and/or; Urine M component (absolute increase must be ≥ 200 mg/24 h) and/or, development of new/definite increase in size of existing bone lesions/soft tissue plasmacytomas, development of hypercalcemia that can be attributed to plasma cell proliferative disorder.
- Time to Progression (TTP) [ Time Frame: Up to 5 years ]
TTP is defined as the time from the first dose of any study drug treatment to the date of the first documented progressive disease (PD). PD: Increase of 25% from lowest response value in any of following: Serum M component with increase ≥ 0.5 gm/dL; serum M component increases ≥1 gm/dL are sufficient to define relapse if starting M component is ≥ 5 gm/dL and/or; Urine M component (absolute increase must be ≥ 200 mg/24 h) and/or, development of new/definite increase in size of existing bone lesions/soft tissue plasmacytomas, development of hypercalcemia that can be attributed to plasma cell proliferative disorder.
- Overall Survival (OS) [ Time Frame: Up to 5 years ]
OS is defined as the time from the date of first dose of any study drug treatment to the date of death.
- Overall Response Rate (ORR) [ Time Frame: Up to 5 years ]
ORR is defined as participants with complete response (CR), VGPR and partial response (PR). CR: Negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow; normal FLC ratio of 0.26-1.65; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein + urine M-protein level <100 mg/24 hours; and PR: ≥50% reduction of serum M protein and reduction in 24-hour urinary M protein by ≥90%/to <200 mg/24 h; In addition, if present at baseline, ≥50% reduction in size of soft tissue plasmacytomas; no known evidence of progressive/new bone lesions.
- Time To Response (TTR) [ Time Frame: Up to 5 years ]
TTR is defined as the time from first dose of any study drug treatment to the date of first documentation of PR or better. PR is defined as ≥50% reduction of serum M protein and reduction in 24-hour urinary M protein by ≥90%/to <200 mg/24 h; In addition, if present at baseline, ≥50% reduction in size of soft tissue plasmacytomas; no known evidence of progressive/new bone lesions.
- Duration of Response (DOR) [ Time Frame: Up to 5 years ]
DOR is defined as the time from the date of first documentation of PR or better to the date of the first documented PD among participants who responded to the treatment. PR is defined as ≥50% reduction of serum M protein and reduction in 24-hour urinary M protein by ≥90%/to <200 mg/24 h; In addition if present at baseline, ≥50% reduction in size of soft tissue plasmacytomas; no known evidence of progressive/new bone lesions.

Phase : II

Stade : NA

2, 3, 4, Rechute, Réfractaire
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 : - Have measurable disease by at least 1 of the following measurements:
* serum M-protein ≥1 gm/dL (≥10 gm/L).
* urine M-protein ≥200 mg/24 hours.
- Have documented evidence of progressive disease (PD) on or after their last regimen as defined by IMWG criteria. All participants must have received between 1 to 3 prior therapies for MM (a prior therapy is defined as 2 or more cycles of therapy given as a treatment plan for MM [eg, a single-agent or combination therapy or a sequence of planned treatments such as induction therapy followed by autologous stem cell transplant (SCT) and then consolidation and/or maintenance therapy]).
- Have achieved a response (partial response (PR) or better) to at least 1 prior therapy.
- Have an Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2.
- Must meet the following laboratory criteria:
* Absolute neutrophil count (ANC) ≥1000/mm3.
* Platelet count ≥75,000/mm3.
* Total bilirubin ≤1.5 x the upper limit of the normal range (ULN) (except for Gilbert syndrome: direct bilirubin ≤2 x ULN).
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x ULN.
* Calculated creatinine clearance ≥50 mL/min.

Critères de non-inclusion : - Have undergone prior allogenic bone marrow transplantation.
- Have received prior ixazomib at any time or daratumumab or other anti-CD38 therapies, except as part of initial therapy if this was stopped to move on to SCT and the participants did not progress on anti-CD38 treatment.
- Are refractory to bortezomib or carfilzomib at the last exposure before this study (defined as participants having PD while receiving bortezomib or carfilzomib therapy or within 60 days after ending bortezomib or carfilzomib therapy).
- Are planning to undergo SCT prior to PD on this study (ie, these participants should not be enrolled in order to reduce disease burden prior to transplant).
- Are receiving systemic treatment with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital, St. John's wort) within 14 days before randomization.
- Has received autologous SCT within 12 weeks before the date of study treatment.
- With known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal. Note: FEV1 testing is required for participants suspected of having COPD and participants must be excluded if FEV1 is <50% of predicted normal.
participants with Grade 2 or higher residual toxicities from prior therapy (including Grade 2 or higher peripheral neuropathy or any grade neuropathy with pain; excluding alopecia). This includes recovery from any major surgery. Note: Participants with planned surgical to be conducted under local anesthesia may participate. Kyphoplasty or vertebroplasty are not considered major surgery.
- Has uncontrolled clinically significant cardiac disease, including myocardial infarction within 6 months before date of study entry or unstable or uncontrolled angina, congestive heart failure, New York Heart Association (NYHA) Class III-IV, uncontrolled cardiac arrhythmia (Grade 2 or higher).
- With ongoing or active systemic infection requiring intravenous (IV) medical management, known human immunodeficiency virus (HIV-RNA) positive, known hepatitis B surface antigen seropositive, or known hepatitis C virus-RNA positive. Note: Participants who have positive hepatitis B core antibody can be enrolled but must have hepatitis B virus-DNA negative. Participants who have positive hepatitis C antibody can be enrolled but must have hepatitis C virus-RNA negative.
-Diagnosed or treated for another malignancy within 2 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT03439293
Promoteur :
TAKEDA Pharmaceuticals
Type de sponsor : Industriel
TAKEDA Pharmaceuticals
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 :
Professeur Thierry FACON

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

Statut de l'essai : CLOS

MAJ : 22/10/2019