Chronic Lymphocytic Leukemia Clinical Trial

Efficacy and Safety of Nemtabrutinib (MK-1026) in Participants With Hematologic Malignancies (MK-1026-003)

Summary

The purpose of this study is to evaluate the safety and efficacy of nemtabrutinib (formerly ARQ 531) in participants with hematologic malignancies of leukemia-cll/" >chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), Richter's transformation, marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and Waldenström's macroglobulinemia (WM).

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Full Description

This study will be performed in 2 parts: Dose Escalation and Confirmation (Part 1) and Cohort Expansion (Part 2). Following determination of a recommended phase 2 dose (RP2D) in Part 1, the study plans to proceed with Part 2 using 8 disease-specific expansion cohorts (Cohorts A to H).

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7 days prior to allocation
Has a life expectancy of at least 3 months, based on the investigator assessment
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 viral load prior to randomization
Participants with history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
Has adequate organ function
Male participants agree to refrain from donating sperm and agree to either remain abstinent from heterosexual intercourse as their preferred and usual lifestyle OR agree to use contraception, during the intervention period and for 12 days after last dose of study intervention
Female participants not pregnant or breastfeeding are eligible to participate if not a woman of childbearing potential (WOCBP), or if a WOCBP they either use a contraceptive method that is highly effective OR remain abstinent from heterosexual intercourse as their preferred and usual lifestyle during the intervention period and for at least 30 days after the last dose of study intervention
Participants with HIV are eligible if they meet all of the following: the CD4 count is >350 cells/uL at screening, the HIV viral load is below the detectable level, are on a stable ART regimen for at least 4 weeks prior to study entry, and are compliant with their ART

Part 1 and Part 2 (Cohorts A to C)

Has a confirmed diagnosis of CLL/SLL with

At least 2 lines of prior therapy (Part 1 only)
Part 2 Cohort A: CLL/SLL participants who are relapsed or refractory to prior therapy with a covalent, irreversible Bruton's tyrosine kinase inhibitor (BTKi), and a B-cell lymphoma 2 inhibitor (BCL2i). CLL participants must have received and failed, been intolerant to, or determined by their treating physician to be a poor phosphoinositide 3-kinase inhibitor (PI3Ki) candidate or ineligible for a PI3Ki per local guidelines
Part 2 Cohort B: CLL/SLL participants who are relapsed or refractory following at least 1 line of prior therapy and are BTKi treatment naive
Part 2 Cohort C: CLL/SLL participants with 17p deletion or tumor protein p53 (TP53) mutation who are relapsed or refractory following at least 1 line of prior therapy
Has active disease for CLL/SLL clearly documented to initiate therapy
Has evaluable core or excisional lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy at Screening (optional for participants enrolling in Part 1)

Part 2 (Cohorts D to G)

Has a confirmed diagnosis of and response to previous treatment of one of the following:

Participants with Richter's transformation who are relapsed or refractory following at least 1 line of prior therapy (Cohort D)
Participants with pathologically confirmed MCL, documented by either overexpression of cyclin D1 or t(11;14), who are relapsed or are refractory to chemoimmunotherapy and a covalent irreversible BTKi (Cohort E)
Participants with MZL (including splenic, nodal, and extra nodal MZL) who are relapsed or refractory to chemoimmunotherapy and a covalent irreversible BTKi (Cohort F)
Participants with FL who are relapsed or refractory to chemoimmunotherapy, immunomodulatory agents (i.e. lenalidomide plus rituximab) (Cohort G)
Have measurable disease defined as at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral CT scan
Has a lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy at Screening

Part 2 (Cohort H): confirmed diagnosis of WM; participants who are relapsed or refractory to standard therapies for WM including chemoimmunotherapy and a covalent irreversible BTKi

Has active disease defined as 1 of the following: systemic symptoms, physical findings, laboratory abnormalities, coexisting disease
Has measurable disease, satisfying any of the following: at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral CT scan (minimum measurement must be >15 mm in the longest diameter or >10 mm in the short axis); IgM ≥450 mg/dL; or bone marrow infiltration of 10%
Has fresh bone marrow aspirate or a lymph node biopsy for biomarker analysis at Screening or a lymph node biopsy from an archival

Exclusion Criteria:

Has active HBV/HCV infection (Part 1 and Part 2)
Has a history of malignancy ≤3 years prior to providing documented informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
Has active central nervous system (CNS) disease
Has an active infection requiring systemic therapy
Has received prior systemic anti-cancer therapy within 4 weeks prior to allocation
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
Has any clinically significant gastrointestinal abnormalities that might alter absorption
History of bleeding disorders

Study is for people with:

Chronic Lymphocytic Leukemia

Phase:

Phase 2

Estimated Enrollment:

450

Study ID:

NCT04728893

Recruitment Status:

Recruiting

Sponsor:

Merck Sharp & Dohme LLC

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There are 48 Locations for this study

See Locations Near You

Lundquist Institute for Biomedical Innovation at Harbor-UCLA-Hematology and Medical Oncology ( Site
Torrance California, 90502, United States More Info
Study Coordinator
Contact
424-201-3000
John Theurer Cancer Center at Hackensack University Medical Center ( Site 2704)
Hackensack New Jersey, 07601, United States More Info
Study Coordinator
Contact
551-996-3003
Medical Oncology Associates (Summit Cancer Centers) ( Site 2710)
Spokane Washington, 99208, United States More Info
Study Coordinator
Contact
509-462-2273
Hospital Aleman ( Site 0102)
Ciudad Autonoma de Buenos Aires Buenos Aires, C1118, Argentina More Info
Study Coordinator
Contact
+541148277000
Centro de Educación Médica e Investigaciones Clínicas (CEMIC) ( Site 0103)
Buenos Aires Caba, C1431, Argentina More Info
Study Coordinator
Contact
+541152990247
FUNDALEU ( Site 0104)
Caba , C1114, Argentina More Info
Study Coordinator
Contact
5411 48771046
Hospital Privado Universitario de Córdoba ( Site 0107)
Cordoba , X5016, Argentina More Info
Study Coordinator
Contact
+54-11-1569634187
Nepean Hospital-Nepean Cancer Care Centre ( Site 0204)
Sydney New South Wales, 2747, Australia More Info
Study Coordinator
Contact
+61247343500
Box Hill Hospital ( Site 0203)
Box Hill Victoria, 3128, Australia More Info
Study Coordinator
Contact
+611300342255
Instituto Nacional do Cancer Jose Alencar Gomes da Silva INCA ( Site 0300)
Rio de Janeiro , 20231, Brazil More Info
Study Coordinator
Contact
+552132076564
BP - A Beneficencia Portuguesa de São Paulo ( Site 0302)
Sao Paulo , 01321, Brazil More Info
Study Coordinator
Contact
+551134744249
Hospital Paulistano - Amil Clinical Research ( Site 0311)
Sao Paulo , 01321, Brazil More Info
Study Coordinator
Contact
+551130161340
Tom Baker Cancer Centre ( Site 0401)
Calgary Alberta, T4N 4, Canada More Info
Study Coordinator
Contact
4035213723
The Ottawa Hospital ( Site 0404)
Ottawa Ontario, K1H 8, Canada More Info
Study Coordinator
Contact
613 737-7700
Jewish General Hospital ( Site 0400)
Montreal Quebec, H3T 1, Canada More Info
Study Coordinator
Contact
5143408222 x 24572
Institut Paoli-Calmettes ( Site 0803)
Marseille Bouches-du-Rhone, 13009, France More Info
Study Coordinator
Contact
+33491223537
Centre Hospitalier Lyon-Sud ( Site 0804)
Pierre Benite Rhone-Alpes, 69495, France More Info
Study Coordinator
Contact
+33478864348
Hopital Saint Louis ( Site 0805)
Paris , 75010, France More Info
Study Coordinator
Contact
33142499236
Ha Emek Medical Center ( Site 1305)
Afula , 18341, Israel More Info
Study Coordinator
Contact
972-46494052
Soroka Medical Center ( Site 1307)
Beer-Sheva , 84101, Israel More Info
Study Coordinator
Contact
+972544203424
Rambam Medical Center ( Site 1301)
Haifa , 31096, Israel More Info
Study Coordinator
Contact
+97247772547
Hadassah Ein Karem Jerusalem ( Site 1300)
Jerusalem , 91120, Israel More Info
Study Coordinator
Contact
+97226778180
Chaim Sheba Medical Center ( Site 1302)
Ramat Gan , 52620, Israel More Info
Study Coordinator
Contact
+972526669155
Sourasky Medical Center ( Site 1303)
Tel Aviv , 64239, Israel More Info
Study Coordinator
Contact
+97236973782
A.O. Universitaria Policlinico S. Orsola-Malpighi ( Site 1400)
Bologna , 40138, Italy More Info
Study Coordinator
Contact
+390516363680
ASST Spedali Civili di Brescia ( Site 1408)
Brescia , 25123, Italy More Info
Study Coordinator
Contact
+39 0303996416
IRCCS Ospedale San Raffaele ( Site 1402)
Milano , 20132, Italy More Info
Study Coordinator
Contact
00390226434797
Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1403)
Napoli , 80131, Italy More Info
Study Coordinator
Contact
+39 0815903 382
Fondazione IRCCS Policlinico San Matteo ( Site 1407)
Pavia , 27100, Italy More Info
Study Coordinator
Contact
+39 0382503084
IRCCS - Arcispedale Santa Maria Nuova ( Site 1405)
Reggio Emilia , 42123, Italy More Info
Study Coordinator
Contact
+39 0522295654
Uniwersytecki Szpital Kliniczny-Klinika Hematologii, Nowotworow Krwi i Transplantacji Szpiku ( Site
Wroclaw Dolnoslaskie, 50-36, Poland More Info
Study Coordinator
Contact
+48717842576
Pratia MCM Krakow ( Site 1601)
Krakow Malopolskie, 30-51, Poland More Info
Study Coordinator
Contact
48 12 2954135
Szpital Wojewódzki w Opolu-Hematology Department ( Site 1607)
Opole Opolskie, 45-06, Poland More Info
Study Coordinator
Contact
774433100
Szpitale Pomorskie Sp. z o.o. ( Site 1600)
Gdynia Pomorskie, 81-51, Poland More Info
Study Coordinator
Contact
48587260102
Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals ( Site 2000)
Hospitalet de Llobregat Barcelona, 08908, Spain More Info
Study Coordinator
Contact
+34932607750
Hospital Universitari Vall d'Hebron ( Site 2001)
Barcelona , 08035, Spain More Info
Study Coordinator
Contact
+34934893806
Hospital Universitario 12 de Octubre ( Site 2003)
Madrid , 28041, Spain More Info
Study Coordinator
Contact
+34917792809
Hospital Universitario de Salamanca ( Site 2002)
Salamanca , 37007, Spain More Info
Study Coordinator
Contact
+34 923 29 11 00 Ext. 55974
Inselspital Bern ( Site 2303)
Bern Berne, 3010, Switzerland More Info
Study Coordinator
Contact
+41316329023
Istituto Oncologica della Svizzera Italiana (IOSI) ( Site 2302)
Bellinzona Ticino, 6500, Switzerland More Info
Study Coordinator
Contact
+41918118540
Ankara Universitesi Tip Fakultesi Cebeci Hastanesi ( Site 2400)
Ankara , 06590, Turkey More Info
Study Coordinator
Contact
+903125957099
VKV Amerikan Hastanesi ( Site 2403)
Istanbul , 34365, Turkey More Info
Study Coordinator
Contact
+905322566160
Dokuz Eylül Üniversitesi-Hematology ( Site 2402)
Izmir , 35340, Turkey More Info
Study Coordinator
Contact
+905425151780
Kyiv City Clinical Hospital 9 ( Site 2502)
Kyiv , 04112, Ukraine
Nottingham University Hospitals NHS Trust. City Hospital Campus ( Site 2601)
Nottingham England, NG5 1, United Kingdom More Info
Study Coordinator
Contact
+441159691169
GenesisCare - Windsor ( Site 2608)
Windsor England, SL4 3, United Kingdom More Info
Study Coordinator
Contact
+447989474250
GenesisCare - Oxford ( Site 2607)
Oxford Oxfordshire, OX4 6, United Kingdom More Info
Study Coordinator
Contact
+447989474250
The Royal Marsden NHS Foundation Trust. ( Site 2606)
London Surrey, SM3 5, United Kingdom More Info
Study Coordinator
Contact
02089156773
The Christie NHS Foundation Trust ( Site 2602)
Manchester , M20 4, United Kingdom More Info
Study Coordinator
Contact
01619561217

How clear is this clinincal trial information?

Study is for people with:

Chronic Lymphocytic Leukemia

Phase:

Phase 2

Estimated Enrollment:

450

Study ID:

NCT04728893

Recruitment Status:

Recruiting

Sponsor:


Merck Sharp & Dohme LLC

How clear is this clinincal trial information?

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