A Phase 3, Open-label, Randomized Study to Compare the Efficacy and Safety of Nemtabrutinib (MK-1026) Plus Venetoclax Versus Venetoclax Plus Rituximab in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Following at Least 1 Prior Therapy (BELLWAVE-010)
ESTADO CLÍNICO
Reclutando
FASE/S DEL ENSAYO
Fase III
PATOLOGÍA
Coagulopatías hemorrágicas, Leucemia linfática crónica y otros SLPC, Leucemia mieloide aguda, Trasplante de progenitores hematopoyéticos, Leucemia mieloide crónica, Linfoma, Leucemia
CENTRO INVESTIGADOR
H.U. Quirónsalud Madrid
INVESTIGADOR PRINCIPAL
Carmen Martínez Chamorro
FECHA DE APERTURA
Noviembre, 2023
FECHA DE CIERRE
,
CRITERIOS DE INCLUSIÓN
Confirmed diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and active disease clearly documented to initiate therapy
Participants with human immunodeficiency virus (HIV) 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 is eligible to participate if not pregnant or breastfeeding and is 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.
Deletion (Del) (17p) status, tumor protein 53 (TP53) mutation status, and immunoglobulin heavy chain gene (IGHV) 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) 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 is eligible to participate if not pregnant or breastfeeding and is 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.
Deletion (Del) (17p) status, tumor protein 53 (TP53) mutation status, and immunoglobulin heavy chain gene (IGHV) 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.
CRITERIOS DE EXCLUSIÓN
Has active hepatitis B virus/ hepatitis C virus (HBV/HCV) infection.
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) within 12 months before randomization or has received prior radiotherapy within 2 weeks of start of study intervention, or radiation related toxicities, requiring corticosteroids.
Is currently being treated with p-glycoprotein (P-gp) substrates with a narrow therapeutic index, cytochrome P450 3A (CYP3A) strong inducers or inhibitors, or CYP3A moderate inducers
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 known psychiatric or substance use disorder that would interfere with the participants ability to cooperate with the requirements of the study.
Participants who have not adequately recovered from major surgery or have ongoing surgical complications.
Has gastrointestinal (GI) dysfunction that may affect drug absorption.
Has known additional malignancy that is progressing or has required active treatment within the past 2 years.
Has diagnosis of Richter Transformation or active central nervous system (CNS) involvement by CLL/SLL.
Has active infection requiring systemic therapy, such as intravenous (IV) antibiotics, during screening.
HIV-infected participants with a history of Kaposis sarcoma and/or Multicentric Castlemans Disease and/or acquired immune deficiency syndrome (AIDS)-defining opportunistic infection in the past 12 months before screening.
Clinically significant cardiovascular disease.
Has 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) within 12 months before randomization or has received prior radiotherapy within 2 weeks of start of study intervention, or radiation related toxicities, requiring corticosteroids.
Is currently being treated with p-glycoprotein (P-gp) substrates with a narrow therapeutic index, cytochrome P450 3A (CYP3A) strong inducers or inhibitors, or CYP3A moderate inducers
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 known psychiatric or substance use disorder that would interfere with the participants ability to cooperate with the requirements of the study.
Participants who have not adequately recovered from major surgery or have ongoing surgical complications.
Has gastrointestinal (GI) dysfunction that may affect drug absorption.
Has known additional malignancy that is progressing or has required active treatment within the past 2 years.
Has diagnosis of Richter Transformation or active central nervous system (CNS) involvement by CLL/SLL.
Has active infection requiring systemic therapy, such as intravenous (IV) antibiotics, during screening.
HIV-infected participants with a history of Kaposis sarcoma and/or Multicentric Castlemans Disease and/or acquired immune deficiency syndrome (AIDS)-defining opportunistic infection in the past 12 months before screening.
Clinically significant cardiovascular disease.
Has 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).
DESCRIPCIÓN
1. Part 1: To evaluate the safety and tolerability and to confirm the dose of nemtabrutinib in combination with venetoclax 2. Part 2: To compare nemtabrutinib + venetoclax to VR with respect to PFS per 2018 iwCLL criteria, as assessed by BICR
PALABRAS CLAVE
chronic leukemia, donor lymphocyte infusion, factor xi, leukemia, lymphocytic, lymphoma, relapsed/refractory all, small lymphocytic lymphoma
