Trial Title:
A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010)
NCT ID:
NCT05947851
Condition:
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Chronic Lymphocytic
Small-Cell Lymphoma
Lymphoma, Small Lymphocytic
CLL
SLL
Conditions: Official terms:
Lymphoma
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Rituximab
Venetoclax
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
In Part 1, Dose Confirmation will be determined by modified toxicity probability interval
(mTPI) design, where participants will be assigned to two treatment groups, Nemtabrutinib
+ Venetoclax in parallel with Nemtabrutinib + Venetoclax. Part 2 will be an Efficacy
Expansion where all participants will be randomized 1:1 to Nemtabrutinib Part 1 Dose
Selection plus Venetoclax or Venetoclax plus Rituximab (VR) (or Rituximab biosimilar) for
the duration of the study.
Primary purpose:
Treatment
Masking:
Single (Outcomes Assessor)
Intervention:
Intervention type:
Drug
Intervention name:
Nemtabrutinib
Description:
5 and 20 mg tablets
Arm group label:
Nemtabrutinib + Venetoclax
Other name:
ARQ 531
Other name:
MK-1026
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
10, 50, and 100 mg tablets
Arm group label:
Nemtabrutinib + Venetoclax
Arm group label:
Venetoclax + Rituximab
Other name:
ABT-199
Other name:
GDC-0199
Intervention type:
Biological
Intervention name:
Rituximab
Description:
100 mg/10 mL, 500 mg/50 mL (10 mg/mL) IV Infusion
Arm group label:
Venetoclax + Rituximab
Summary:
The purpose of this study is to assess the safety and tolerability and to confirm the
dose of nemtabrutinib in combination with venetoclax in participants with R/R CLL/SLL.
The primary study hypotheses are that the combination of nemtabrutinib plus venetoclax is
superior to VR with respect to progression-free survival (PFS) per 2018 International
Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria as assessed by blinded
independent central review (BICR).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Confirmed diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma
(CLL/SLL) and active disease clearly documented to initiate therapy.
- Deletion (Del) (17p) status, tumor protein 53 (TP53) mutation status, immunoglobulin
heavy chain gene (IGHV) mutation status and Bruton's tyrosine kinase (BTK)-C481
mutation status results required before randomization for Part 2 participants only.
- Relapsed or refractory to at least 1 prior available therapy.
- Have at least 1 marker of disease burden.
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within
7 days before randomization.
- Has a life expectancy of at least 3 months.
- Has the ability to swallow and retain oral medication.
- Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if
they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks
and have undetectable HBV deoxyribonucleic acid (DNA) viral load before
randomization.
- Participants with history of hepatitis C virus (HCV) infection are eligible if HCV
ribonucleic acid (RNA) viral load is undetectable at screening.
- Participants with human immunodeficiency virus (HIV) who meet ALL eligibility
criteria.
- Participants with adequate organ function with specimens collected within 7 days
before the start of study intervention.
- If capable of producing sperm, participant agrees to eliminate Nemtabrutinib: 12
days, Venetoclax: 1 month (30 days), Rituximab (rituximab biosimilar): not
applicable; abstains from penile-vaginal intercourse as their preferred and usual
lifestyle; OR uses prescribed contraception.
- Participant assigned female sex at birth are eligible to participate if not pregnant
or breastfeeding and are not a person of childbearing potential (POCBP) OR is a
POCBP and uses a contraceptive method that is highly effective, has a negative
highly sensitive pregnancy test, and abstains from breastfeeding.
Exclusion Criteria:
- Has an active hepatitis B virus/ hepatitis C virus (HBV/HCV) infection.
- Has gastrointestinal (GI) dysfunction that may affect drug absorption.
- Has a known additional malignancy that is progressing or has required active
treatment within the past 3 years.
- Has diagnosis of Richter Transformation or active central nervous system (CNS)
involvement by CLL/SLL.
- Has an active infection requiring systemic therapy, such as intravenous (IV)
antibiotics, during screening.
- HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric
Castleman's Disease and/or acquired immune deficiency syndrome (AIDS)-defining
opportunistic infection in the past 12 months before screening.
- Has QT interval corrected (QTc) prolongation or other significant electrocardiogram
(ECG) abnormalities.
- Has a known allergy/sensitivity to nemtabrutinib or contraindication to
venetoclax/rituximab (or rituximab biosimilar), or any of the excipients.
- Has history of severe bleeding disorders (eg, hemophilia).
- Has received prior systemic anticancer therapy within 5 half-lives or 4 weeks (if
prior therapy was a monoclonal antibody) before randomization.
- Has received prior B-cell lymphoma 2 inhibitor(s) (BCL2i) including venetoclax or
Non-covalent Bruton's tyrosine kinase inhibitor (BTKi).
- Is currently being treated with p-glycoprotein (P-gp) substrates with a narrow
therapeutic index, cytochrome P450 3A (CYP3A) strong or moderate inducers or CYP3A
strong inhibitors.
- Has received a live or live attenuated vaccine within 30 days before the first dose
of study intervention.
- Has received an investigational agent or has used an investigational device within 4
weeks before study intervention administration.
- Has a known psychiatric or substance use disorder that would interfere with the
participant's ability to cooperate with the requirements of the study.
- Participants who have not adequately recovered from major surgery or have ongoing
surgical complications.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Highlands Oncology Group ( Site 5405)
Address:
City:
Springdale
Zip:
72762
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
479-872-8130
Facility:
Name:
MemorialCare Health System - Long Beach Medical Center ( Site 5421)
Address:
City:
Long Beach
Zip:
90806
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
562-933-1877
Facility:
Name:
Memorial Hospital West ( Site 5410)
Address:
City:
Pembroke Pines
Zip:
33028
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
786-333-9982
Facility:
Name:
Medical Oncology Associates, PS ( Site 5406)
Address:
City:
Spokane
Zip:
99208
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
509-462-2273
Facility:
Name:
University of Wisconsin Hospital and Clinics-Carbone Cancer Center ( Site 5423)
Address:
City:
Madison
Zip:
53792
Country:
United States
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
608-262-9317
Facility:
Name:
Instituto Alexander Fleming ( Site 1005)
Address:
City:
Ciudad Autónoma de Buenos Aires
Zip:
C1426ANZ
Country:
Argentina
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
+5491140510781
Facility:
Name:
Instituto de Investigaciones Clínicas Mar del Plata ( Site 1007)
Address:
City:
Mar del Plata
Zip:
B7600FZO
Country:
Argentina
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
+5492235937663
Facility:
Name:
Centro de Educación Médica e Investigaciones Clínicas (CEMIC)-Hematology ( Site 1002)
Address:
City:
Buenos Aires
Zip:
C1431FWO
Country:
Argentina
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
+5491159785130
Facility:
Name:
Sanatorio Parque ( Site 1003)
Address:
City:
Rosario
Zip:
S2000DSV
Country:
Argentina
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
5493416149812
Facility:
Name:
Centro Medico Fleischer ( Site 1006)
Address:
City:
Buenos Aires
Zip:
1414
Country:
Argentina
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
05491164901040
Facility:
Name:
Hospital Aleman-oncohematologic diseases ( Site 1001)
Address:
City:
Buenos Aires
Zip:
C1118AAT
Country:
Argentina
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
+5491153857234
Facility:
Name:
Royal Adelaide Hospital ( Site 1104)
Address:
City:
Adelaide
Zip:
5000
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
61-8-8222-6934
Facility:
Name:
Western Health-Sunshine & Footscray Hospitals-Cancer Services-Cancer Research ( Site 1103)
Address:
City:
Melbourne
Zip:
3021
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
61395944044
Facility:
Name:
UZ Leuven-Hematology ( Site 1200)
Address:
City:
Leuven
Zip:
3000
Country:
Belgium
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
3216346880
Facility:
Name:
ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO-Pesquisa Clinica ( Site 1308)
Address:
City:
Sao Paulo
Zip:
01246-000
Country:
Brazil
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
+5511999014316
Facility:
Name:
The Moncton Hospital ( Site 1414)
Address:
City:
Moncton
Zip:
E1C 6Z8
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
506-870-2404
Facility:
Name:
Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre ( Site 1402)
Address:
City:
Greenfield Park
Zip:
J4V 2H1
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
450-466-5000 ext 3226
Facility:
Name:
Centre intégré universitaire de santé et de services sociaux de l'Estrie - Centre Hospitalier Univer
Address:
City:
Sherbrooke
Zip:
J1H 5H4
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
819-346-1110 ext 12811
Facility:
Name:
Biocenter ( Site 1507)
Address:
City:
Concepcion
Zip:
4070196
Country:
Chile
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
956284078
Facility:
Name:
IC La Serena Research ( Site 1506)
Address:
City:
La Serena.
Zip:
1720430
Country:
Chile
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
+56951280903
Facility:
Name:
Centro de Estudios Clínicos SAGA-CECSAGA ( Site 1509)
Address:
City:
Santiago
Zip:
7500653
Country:
Chile
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
+56991612199
Facility:
Name:
FALP-UIDO ( Site 1500)
Address:
City:
Santiago
Zip:
7500921
Country:
Chile
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
+56984290128
Facility:
Name:
Clínica Inmunocel ( Site 1511)
Address:
City:
Santiago
Zip:
7580206
Country:
Chile
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
997890202
Facility:
Name:
Fundación Valle del Lili ( Site 1703)
Address:
City:
Cali
Zip:
760032
Country:
Colombia
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
23319090
Facility:
Name:
Hopital Claude Huriez - CHU de Lille ( Site 2107)
Address:
City:
Lille
Zip:
59037
Country:
France
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
+33320444290
Facility:
Name:
Centre Hospitalier Universitaire Estaing ( Site 2105)
Address:
City:
Clermont-Ferrand
Zip:
63100
Country:
France
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
33473750065
Facility:
Name:
CHD Vendee ( Site 2100)
Address:
City:
La Roche-sur-Yon
Zip:
85925
Country:
France
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
0251446173
Facility:
Name:
Klinikum Mutterhaus der Borromäerinnen-Innere Medizin I ( Site 2203)
Address:
City:
Trier
Zip:
54290
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
0049 651 947 2571
Facility:
Name:
Universitätsklinikum Leipzig-Medical Department I - Hematology and Celltherapy ( Site 2201)
Address:
City:
Leipzig
Zip:
04103
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
+49 341 97 13131
Facility:
Name:
Rambam Health Care Campus ( Site 2801)
Address:
City:
Haifa
Zip:
3109601
Country:
Israel
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
97247772541
Facility:
Name:
Hadassah Medical Center-Hemato-Oncology ( Site 2812)
Address:
City:
Jerusalem
Zip:
9112001
Country:
Israel
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
97226778180
Facility:
Name:
Sheba Medical Center-Hemato Oncology ( Site 2809)
Address:
City:
Ramat Gan
Zip:
5265601
Country:
Israel
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
972526669155
Facility:
Name:
Sourasky Medical Center ( Site 2811)
Address:
City:
Tel Aviv
Zip:
6423906
Country:
Israel
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
97236973782
Facility:
Name:
Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare -Azienda Ospedaliera Nazionale SS. Ant
Address:
City:
Alessandria
Zip:
15121
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
+390131206440
Facility:
Name:
Ospedale San Raffaele-Programma di Ricerca Strategica sulla LLC ( Site 2902)
Address:
City:
Milano
Zip:
20132
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
+390226436119
Facility:
Name:
Arcispedale Santa Maria Nuova-Hematology ( Site 2900)
Address:
City:
Reggio Emilia
Zip:
42123
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
3474890239
Facility:
Name:
Auxilio Mutuo Cancer Center ( Site 3900)
Address:
City:
San Juan
Zip:
00918
Country:
Puerto Rico
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
7877582000
Facility:
Name:
Netcare Pretoria East Hospital-Albert Alberts Stem Cell Transplant Centre ( Site 4401)
Address:
City:
Moreletta Park
Zip:
0181
Country:
South Africa
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
27129932555
Facility:
Name:
Groote Schuur Hospital ( Site 4400)
Address:
City:
Cape Town
Zip:
7925
Country:
South Africa
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
0727689024
Facility:
Name:
Haemalife ( Site 4407)
Address:
City:
Kuilsriver
Zip:
7580
Country:
South Africa
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
+27219006277
Facility:
Name:
Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 4601)
Address:
City:
L'Hospitalet Del Llobregat
Zip:
08908
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
+34932607750
Facility:
Name:
HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID ( Site 4602)
Address:
City:
Pozuelo de Alarcon
Zip:
28223
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
914521900
Facility:
Name:
HOSPITAL CLINICO DE VALENCIA-HEMATOLOGY ( Site 4603)
Address:
City:
Valencia
Zip:
46010
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
961973930
Facility:
Name:
Namik Kemal University Medical Faculty-Hematology ( Site 4912)
Address:
City:
Tekirdag
Zip:
59100
Country:
Turkey
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
05326347632
Facility:
Name:
Ankara Universitesi Tip Fakultesi Hastanesi-hematology ( Site 4913)
Address:
City:
Ankara
Zip:
06100
Country:
Turkey
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
05055025050
Facility:
Name:
City Hospital, Nottingham University Hospitals-Hematology ( Site 5002)
Address:
City:
Nottingham
Zip:
NG5 1PF
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
447425788152
Facility:
Name:
University College London Hospital-Cancer Clinical Trials Unit ( Site 5001)
Address:
City:
London-Camden
Zip:
NW1 2PG
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Study Coordinator
Phone:
07877274114
Start date:
August 8, 2023
Completion date:
June 27, 2033
Lead sponsor:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Source:
Merck Sharp & Dohme LLC
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05947851
https://www.merckclinicaltrials.com
https://trialstransparency.merckclinicaltrials.com/Study.aspx?id=1026-010&&kw=1026-010
