Chronic Lymphocytic Leukemia Clinical Trial
Official title:
A Phase 3, Randomized Study to Compare the Efficacy and Safety of Nemtabrutinib Versus Chemoimmunotherapy for Previously Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Without TP53 Aberrations
The purpose of this study is to evaluate the efficacy and safety of nemtabrutinib compared to investigator's choice of fludarabine plus cyclophosphamide plus rituximab (FCR) or bendamustine plus rituximab (BR) in participants with previously untreated CLL/SLL without 17p deletion and/or tumor protein (TP) 53 mutation. The primary hypothesis is that nemtabrutinib is superior to FCR/BR with respect to progression-free survival (PFS).
| Status | Recruiting |
| Enrollment | 300 |
| Est. completion date | March 17, 2031 |
| Est. primary completion date | May 19, 2027 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | The main inclusion and exclusion criteria include but are not limited to the following: Inclusion Criteria: - Confirmed diagnosis of chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) and active disease clearly documented to have a need to initiate therapy - Has previously untreated CLL/SLL participants without tumor protein 53 (TP53) aberrations and documented 11q status and immunoglobulin heavy chain gene (IGHV) mutational status - The ability to swallow and retain oral medication Exclusion Criteria: - Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection - Gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy) - Known additional malignancy that is progressing or has required active treatment within the past 3 years, except basal cell carcinoma of skin, squamous cell carcinoma of skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potential curative therapy - History of severe bleeding disorders - Not adequately recovered from major surgery or has ongoing surgical complications |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Royal Adelaide Hospital ( Site 1105) | Adelaide | South Australia |
| Brazil | Hospital Erasto Gaertner-CEPEP - Pesquisa Clínica ( Site 1317) | Curitiba | Parana |
| Brazil | Hospital Amaral Carvalho-Centro de Pesquisas ( Site 1304) | Jaú | Sao Paulo |
| Brazil | Instituto Nacional de Câncer - INCA-Divisão de Pesquisa Clínica e Desenvolvimento Tecnológico HC1 ( | Rio de Janeiro | |
| Brazil | Hospital Paulistano-Americas Oncologia ( Site 1302) | Sao Paulo | |
| Brazil | A. C. Camargo Cancer Center ( Site 1318) | São Paulo | Sao Paulo |
| Brazil | ICESP - INSTITUTO DO CÂNCER DO ESTADO DE SÃO PAULO-Pesquisa Clinica ( Site 1308) | São Paulo | Sao Paulo |
| Chile | Biocenter ( Site 1507) | Concepción | Biobio |
| Chile | IC La Serena Research ( Site 1506) | La Serena | Coquimbo |
| Chile | Centro de Estudios Clínicos SAGA-CECSAGA ( Site 1509) | Santiago | Region M. De Santiago |
| Chile | Clínica Inmunocel ( Site 1511) | Santiago | Region M. De Santiago |
| Chile | FALP-UIDO ( Site 1500) | Santiago | Region M. De Santiago |
| Chile | James Lind Centro de Investigación del Cáncer ( Site 1503) | Temuco | Araucania |
| China | Peking University Third Hospital ( Site 1602) | Beijing | Beijing |
| China | The First Hospital of Jilin University-Hematology ( Site 1621) | Changchun | Jilin |
| China | Hunan Cancer Hospital ( Site 1615) | Changsha | Hunan |
| China | Xiangya Hospital Central South University-Hematology department ( Site 1616) | Changsha | Hunan |
| China | Chongqing University Cancer Hospital ( Site 1605) | Chongqing | Chongqing |
| China | Chongqing University Three Gorges Hospital ( Site 1609) | Chongqing | Chongqing |
| China | Southern Medical University Nanfang Hospital-Department of Hematopathology ( Site 1607) | Guangzhou | Guangdong |
| China | Sun Yat-sen University Cancer Center ( Site 1608) | Guangzhou | Guangdong |
| China | The Affiliated Hospital of Guizhou Medical University ( Site 1625) | Guiyang | Guizhou |
| China | Hainan General Hospital ( Site 1603) | Haikou | Hainan |
| China | The First Affiliated Hospital, Zhejiang University-Hematology ( Site 1611) | Hangzhou | Zhejiang |
| China | Jiangxi Provincial Cancer Hospital ( Site 1628) | Nanchang | Jiangxi |
| China | The First Affiliated Hospital of Nanchang University ( Site 1614) | Nanchang | Jiangxi |
| China | Fudan University Shanghai Cancer Center ( Site 1606) | Shanghai | Shanghai |
| China | The First Affiliated Hospital of Soochow University-hematology department ( Site 1612) | Suzhou | Jiangsu |
| China | Shanxi Cancer Hospital ( Site 1629) | Taiyuan | Shanxi |
| China | Institute of hematology&blood disease hospital ( Site 1600) | Tianjin | Tianjin |
| China | Tianjin Medical University Cancer Institute & Hospital-lymphoma ( Site 1604) | Tianjin | Tianjin |
| China | Tongji Hospital Tongji Medical,Science & Technology ( Site 1619) | Wuhan | Hubei |
| China | Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 1618) | Wuhan | Hubei |
| China | Shaanxi provincial people's hospital ( Site 1626) | Xi'an | Shaanxi |
| China | The First Affiliated Hospital of Xi'an Jiaotong University ( Site 1617) | Xi'an | Shaanxi |
| China | Henan Cancer Hospital-hematology department ( Site 1613) | Zhengzhou | Henan |
| Colombia | Clini Salud ( Site 1700) | Envigado | Antioquia |
| Colombia | Fundacion Colombiana de Cancerología Clinica Vida ( Site 1707) | Medellin | Antioquia |
| Colombia | Oncologos del Occidente ( Site 1706) | Pereira | Risaralda |
| Colombia | Sociedad De Oncologia Y Hematologia Del Cesar-Oncology ( Site 1704) | Valledupar | Cesar |
| Denmark | Aalborg Universitetshospital, Syd ( Site 1901) | Aalborg | Nordjylland |
| Denmark | Aarhus Universitetshospital, Skejby-Blodsygdomme ( Site 1902) | Aarhus | Midtjylland |
| Denmark | Odense Universitetshospital ( Site 1900) | Odense | Syddanmark |
| Denmark | Vejle Sygehus ( Site 1903) | Vejle | Syddanmark |
| Guatemala | CELAN,S.A ( Site 2403) | Guatemala | |
| Guatemala | MEDI-K CAYALA ( Site 2401) | Guatemala | |
| Guatemala | Oncomedica-Guatemala ( Site 2402) | Guatemala | |
| Hong Kong | Queen Mary Hospital ( Site 2500) | Hksar | |
| Hungary | Heves Vármegyei Markhot Ferenc Oktatókórház és Rendelointézet ( Site 2608) | Eger | Heves |
| Hungary | Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókór-Haematológia osztály ( Site 2602) | Nyiregyhaza | Szabolcs-Szatmar-Bereg |
| Hungary | Fejér Megyei Szent György Egyetemi Oktató Kórház ( Site 2609) | Székesfehérvár | Fejer |
| Malaysia | Hospital Ampang ( Site 3202) | Ampang | Selangor |
| Malaysia | Hospital Sultanah Aminah ( Site 3203) | Johor Bahru | Johor |
| Mexico | Centro de Infusion Superare ( Site 3314) | Ciudad de México | Distrito Federal |
| Mexico | Health Pharma Professional Research S.A. de C.V: ( Site 3301) | Ciudad de México | Distrito Federal |
| Mexico | Centro de Investigacion Clinica Chapultepec ( Site 3309) | Morelia | Michoacan |
| Poland | Uniwersyteckie Centrum Kliniczne-Klinika Hematologii i Transplantologii ( Site 3702) | Gdansk | Pomorskie |
| Poland | Pratia Onkologia Katowice ( Site 3705) | Katowice | Slaskie |
| Poland | Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zakl-Klinika Hematologii i Transplantacji S | Kielce | Swietokrzyskie |
| Poland | Samodzielny Publiczny Szpital Kliniczny nr 1-Department of Haematooncology and Bone Marrow Transpla | Lublin | Lubelskie |
| Poland | Samodzielny Publiczny Zaklad Opieki Zdrowotnej MSWiA z Warmi-Oddzial Kliniczny Hematologii ( Site 37 | Olsztyn | Warminsko-mazurskie |
| Poland | Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworów Ukladu Chlonnego ( S | Warszawa | Mazowieckie |
| Romania | Spitalul Clinic Col?ea ( Site 4000) | Bucure?ti | Bucuresti |
| Romania | Spitalul Clinic Col?ea ( Site 4001) | Bucure?ti | Bucuresti |
| Romania | Institutul Oncologic Cluj ( Site 4002) | Cluj | |
| Singapore | National Cancer Centre Singapore ( Site 4200) | Singapore | Central Singapore |
| Singapore | Tan Tock Seng Hospital ( Site 4202) | Singapore | Central Singapore |
| South Africa | Groote Schuur Hospital-Clinical Haematology ( Site 4400) | Cape Town | Western Cape |
| South Africa | Netcare Pretoria East Hospital-Albert Alberts Stem Cell Transplant Centre ( Site 4401) | Centurion | Gauteng |
| South Africa | Wits Clinical Research ( Site 4403) | Johannesburg | Gauteng |
| South Africa | Haemalife ( Site 4407) | Kuilsriver | Western Cape |
| South Africa | Constantiaberg Haematology ( Site 4408) | Plumstead | Western Cape |
| Taiwan | Chang Gung Memorial Hospital at Kaohsiung-Division of Hematology and Oncology ( Site 4700) | Kaohsiung | |
| Taiwan | National Cheng Kung University Hospital ( Site 4701) | Tainan | |
| Taiwan | National Taiwan University Hospital ( Site 4704) | Taipei | |
| Turkey | Ankara Universitesi Tip Fakultesi Hastanesi-hematology ( Site 4913) | Ankara | |
| Turkey | TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi ( Site 4906) | Istanbul | |
| Turkey | Ege Universitesi Hastanesi ( Site 4902) | Izmir | |
| Turkey | Mega Medipol-Hematology ( Site 4904) | Stanbul | Istanbul |
| Turkey | Namik Kemal University Medical Faculty-Hematology ( Site 4912) | Suleymanpasa | Tekirdas |
| Ukraine | MNPE ClinCenter of Oncology,Hematology,Transplantology and Palliative Care of CherkasyRegCouncil ( S | Cherkassy | Cherkaska Oblast |
| Ukraine | Communal non-profit enterprise "Regional clinical hospital o-Hematology Department ( Site 5113) | Ivano-Frankivsk | Ivano-Frankivska Oblast |
| Ukraine | National Research Center for Radiation Medicine of National Academy of Medical Sciences of Ukraine ( | Kyiv | |
| Ukraine | Nonprofit Organization National Cancer Institute ( Site 5103) | Kyiv | Kyivska Oblast |
| Ukraine | Public Non-Profit Enterprise Kyiv City Clinical Hospital #9 -Hematology department #1 ( Site 5111) | Kyiv | |
| Ukraine | Institute of Blood Pathology and Transfusion Medicine of National A?ademy of Medical Sciences of Ukr | Lviv | Lvivska Oblast |
| United States | Clermont Oncology Center ( Site 5224) | Clermont | Florida |
| United States | Hattiesburg Clinic Hematology/Oncology ( Site 5216) | Hattiesburg | Mississippi |
| United States | Medical Oncology Associates, PS ( Site 5206) | Spokane | Washington |
| United States | Highlands Oncology Group ( Site 5205) | Springdale | Arkansas |
| Lead Sponsor | Collaborator |
|---|---|
| Merck Sharp & Dohme LLC |
United States, Australia, Brazil, Chile, China, Colombia, Denmark, Guatemala, Hong Kong, Hungary, Malaysia, Mexico, Poland, Romania, Singapore, South Africa, Taiwan, Turkey, Ukraine,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Progression-Free Survival (PFS) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria 2018 as Assessed by Blinded Independent Central Review (BICR) | PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. PD is evaluated per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria 2018 as assessed by blinded independent central review (BICR). | Up to approximately 49 months | |
| Secondary | Overall Survival (OS) | OS is defined as the time from randomization to death due to any cause. | Up to approximately 94 months | |
| Secondary | Objective Response Rate (ORR) per iwCLL Criteria 2018 as Assessed by BICR | ORR is defined as the percentage of participants with complete response (CR), complete response with an incomplete recovery of the participant's bone marrow (CRi), nodular partial response (nPR), or Partial response (PR), per iwCLL criteria 2018 as assessed by BICR. | Up to approximately 36 months | |
| Secondary | Duration of Response (DOR) per iwCLL Criteria 2018 as Assessed by BICR | For participants who demonstrate a CR, CRi, nPR, or PR per iwCLL criteria as assessed by BICR, DOR is defined as the time from the first documented evidence of CR, CRi, nPR, or PR that led to response until disease progression or death due to any cause, whichever occurs first. | Up to approximately 94 months | |
| Secondary | Number of Participants Who Experience an Adverse Event (AE) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. | Up to approximately 94 months | |
| Secondary | Number of Participants Who Discontinue Study Treatment Due to an AE | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. | Up to approximately 94 months |
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