En studie för att utvärdera effekten av Venetoclax på deltagare som får en kovalent Brutons tyrosinkinashämmare (cBTKi) för första linjens kronisk lymfatisk leukemi (1L CLL) för att uppnå djupa varaktiga remissioner för att tillåta en period utan behandling (BRAVE)
Fas II, öppen etikett, prospektiv enarmad, multicenter klinisk prövning för att utvärdera om tillägg av Venetoclax till patienter på kovalent BTKi för 1L CLL kan uppnå djupa varaktiga remissioner (genom UMRD 10^-4) för att tillåta en period utan behandling
The main purpose of the study is to evaluate if adding venetoclax to participants receiving cBTKi for the 1L CLL can achieve deep durable remissions of undetectable measurable residual disease [uMRD < or 10^-4 in peripheral blood (PB)] by end of combination treatment (EOCT) to allow off-treatment period.
The acronym BRAVE stands for Btki Responders to Achieve deep remission (or off-treatment periods) with VEnetoclax.
Studieöversikt
Status
Betingelser
Intervention / Behandling
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 2
Kontakter och platser
Studieorter
-
-
Arkansas
-
Springdale, Arkansas, Förenta staterna, 72762
- Highlands Oncology Group
-
-
Colorado
-
Aurora, Colorado, Förenta staterna, 80012-5405
- Rocky Mountain Cancer Centers (Aurora) - USOR
-
-
Florida
-
Jacksonville, Florida, Förenta staterna, 32256-6932
- Cancer Specialists of North Florida
-
-
Indiana
-
Fort Wayne, Indiana, Förenta staterna, 46804
- Fort Wayne Medical Oncology and Hematology, Inc
-
-
Iowa
-
Des Moines, Iowa, Förenta staterna, 50314-3030
- Mission Blood and Cancer - MercyOne Cancer Center
-
-
Maryland
-
Bethesda, Maryland, Förenta staterna, 20817-1915
- American Oncology Partners of Maryland, PA
-
-
Massachusetts
-
Boston, Massachusetts, Förenta staterna, 02215-5418
- Dana-Farber Cancer Institute - Hematologic Oncology Treatment Center
-
-
Nebraska
-
Grand Island, Nebraska, Förenta staterna, 68803
- Nebraska Cancer Specialists St Francis - Grand Island
-
Omaha, Nebraska, Förenta staterna, 68130-2042
- Nebraska Cancer Specialists
-
-
New Jersey
-
East Brunswick, New Jersey, Förenta staterna, 08816-4096
- Astera Cancer Care East Brunswick
-
-
New Mexico
-
Farmington, New Mexico, Förenta staterna, 87401
- San Juan Oncology Associates, PC
-
-
Ohio
-
Cincinnati, Ohio, Förenta staterna, 45236-2725
- Oncology Hematology Care Inc - Cincinnati - USOR
-
Columbus, Ohio, Förenta staterna, 43210
- Ohio State University
-
-
Oregon
-
Eugene, Oregon, Förenta staterna, 97401-6043
- Willamette Valley Cancer Institute and Research Center
-
Medford, Oregon, Förenta staterna, 97504-8332
- Asante Rogue Regional Medical Center
-
-
Tennessee
-
Chattanooga, Tennessee, Förenta staterna, 37404
- Tennessee Oncology, PLLC - Chattanooga
-
Nashville, Tennessee, Förenta staterna, 37203
- Tennessee Oncology - Midtown
-
-
Texas
-
Houston, Texas, Förenta staterna, 77030
- MD Anderson Cancer Center
-
Tyler, Texas, Förenta staterna, 75702
- Texas Oncology- Northeast Texas
-
-
Wisconsin
-
Milwaukee, Wisconsin, Förenta staterna, 53226
- Medical College of Wisconsin
-
-
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
Inclusion Criteria:
- Diagnosed with CLL and currently receiving a stable dose of cBTKi (i.e., ibrutinib, acalabrutinib, or zanubrutinib) for at least 6 months for 1L treatment with a response of at least a PR per iwCLL criteria
- Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to (</=) 2
- Adequate renal and liver function
Exclusion Criteria:
- Prior B-cell lymphoma (Bcl-2) inhibitor therapy
- Anti-cluster of differentiation 20 (CD20) therapy within the month prior to screening
- Progressive or stable disease on cBTKi
- Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (Richter's transformation or pro-lymphocytic leukemia)
- History of cardiomyopathy
- Hypersensitivity to venetoclax or to any of the excipients (e.g., trehalose)
- Clinically significant cardiovascular disease
- Active bleeding or history of bleeding diathesis
- Pregnant women and nursing mothers
- Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: N/A
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Experimentell: Venetoclax Added to cBTKi (Commercially Prescribed)
Participants will receive venetoclax, orally, once daily (QD) with a starting ramp-up dose of 20 milligrams (mg) on Day 1 of Cycle 1 (cycle length= 28 days). The dose will increase weekly; thereafter, treatment will continue with venetoclax at the target dose of 400 mg, QD from Week 5 up to Day 28 of Cycle 12. Participant will discontinue from venetoclax and/or cBTKi after 12 cycles. Participants with detectable measurable residual disease with the presence of less than 1 CLL cell in 10,000 leukocytes (< 10^-4) (MRD4) or uMRD4 with partial response (PR) may continue receiving cBTKi-monotherapy (i.e. ibrutinib or acalabrutinib, or zanubrutinib) as previously prescribed by the investigator according to the prescribing label. |
Venetoclax tablets will be administered as per the schedule specified in the arm.
Andra namn:
Commercially available cBTKi (ibrutinib or acalabrutinib, or zanubrutinib) will be administered in accordance with its prescribing label. |
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
uMRD4 Rate at EOCT
Tidsram: Cycle 12 Day 28 (Cycle length= 28 Days)
|
uMRD4 will be assessed using next generation sequencing (NGS) (sensitivity 10^-4) from PB. |
Cycle 12 Day 28 (Cycle length= 28 Days)
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
CR/CRi Rate at EOCT as Determined by the Investigator According to International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Guidelines
Tidsram: Up to approximately 12 months
|
Complete response (CR)/complete response with incomplete recovery of the bone marrow (CRi) rate is defined as the percentage of participants with a CR or CRi at EOCT, as determined by the investigator according to the iwCLL. |
Up to approximately 12 months
|
|
PR Rate at EOCT as Determined by the Investigator According to iwCLL Guidelines
Tidsram: Up to approximately 12 months
|
PR rate is defined as the percentage of participants with a PR at EOCT, as determined by the investigator according to the iwCLL. |
Up to approximately 12 months
|
|
Overall Response Rate (ORR) at EOCT as Determined by the Investigator According to iwCLL Guidelines
Tidsram: Up to approximately 12 months
|
ORR is defined as the percentage of participants with a CR/CRi or PR at EOCT, as determined by the investigator according to the iwCLL. |
Up to approximately 12 months
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Tidsram: Up to approximately 13 months
|
AE and SAEs will be collected as part of this study at baseline and every clinical visit, until 30 days after the final dose of study treatment. |
Up to approximately 13 months
|
|
Number of Participants Who Withdrew Prematurely from the Study
Tidsram: Up to approximately 12 months
|
Participants who discontinued treatment before Cycle 12 Day 28 (cycle length= 28 days). |
Up to approximately 12 months
|
|
Overall Survival (OS)
Tidsram: Up to approximately 48 months
|
OS is defined as the time from the first study treatment to death from any cause. |
Up to approximately 48 months
|
|
Progression-free Survival (PFS) as Determined by the Investigator According to iwCLL Guidelines
Tidsram: Up to approximately 48 months
|
PFS is defined as the time from the first study treatment to the first occurrence of disease progression (PD) or death from any cause during study, whichever occurs first, as determined by the investigator according to the iwCLL. |
Up to approximately 48 months
|
|
Event-free Survival (EFS) as Determined by the Investigator According to iwCLL Guidelines
Tidsram: Up to approximately 48 months
|
EFS is defined as the time from the first study treatment to the first occurrence of PD, anti-leukemic treatment subsequent to the study treatment, or death from any cause during study, whichever occurs first, as determined by the investigator according to the iwCLL. |
Up to approximately 48 months
|
|
Duration of Response (DOR) in Participants With CR/CRi or PR as Determined by the Investigator According to iwCLL Guidelines
Tidsram: Up to approximately 12 months
|
DOR is defined as the time from the first occurrence of a documented objective response (i.e., CR/CRi or PR) to PD or death from any cause, whichever occurs first, as determined by the investigator according to the iwCLL. |
Up to approximately 12 months
|
|
DOR in Participants With CR or CRi as Determined by the Investigator According to iwCLL Guidelines
Tidsram: Up to approximately 12 months
|
DOR is defined as the time from the first occurrence of a documented objective response (i.e., CR or CRi ) to PD or death from any cause, whichever occurs first, as determined by the investigator according to the iwCLL. |
Up to approximately 12 months
|
|
Time to Next CLL Treatment (TTNT)
Tidsram: Up to approximately 12 months
|
TTNT is defined as the time from the first study treatment to the start of anti-leukemic treatment subsequent to the study treatment or death, whichever occurs first. |
Up to approximately 12 months
|
Samarbetspartners och utredare
Sponsor
Utredare
- Studierektor: Clinical Trials, Hoffmann-La Roche
Studieavstämningsdatum
Studera stora datum
Studiestart (Faktisk)
Primärt slutförande (Beräknad)
Avslutad studie (Beräknad)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Faktisk)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
- Patologiska processer
- Neoplasmer
- Kronisk sjukdom
- Sjukdomsegenskaper
- Immunsystemets sjukdomar
- Neoplasmer efter histologisk typ
- Hematologiska sjukdomar
- Lymfatiska sjukdomar
- Lymfoproliferativa störningar
- Immunproliferativa störningar
- Leukemi, B-cell
- Leukemi, lymfoid
- Leukemi
- Patologiska tillstånd, tecken och symtom
- Hemiska och lymfsjukdomar
- Leukemi, lymfocytisk, kronisk, B-cell
- venetoklax
Andra studie-ID-nummer
- ML45219
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
IPD-planbeskrivning
For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing
Läkemedels- och apparatinformation, studiedokument
Studerar en amerikansk FDA-reglerad läkemedelsprodukt
Studerar en amerikansk FDA-reglerad produktprodukt
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .