A Phase 2 Study of Emavusertib in Combination with an Approved Bruton Tyrosine Kinase Inhibitor in Patients with Chronic Lymphocytic Leukemia and Other B-cell Malignancies
ESTADO CLÍNICO
Reclutando
FASE/S DEL ENSAYO
Fase II
PATOLOGÍA
Leucemia linfática crónica y otros SLPC, Trombosis y Anticoagulantes, Leucemia mieloide crónica, Linfoma, Leucemia
CENTRO INVESTIGADOR
H. Fundación Jiménez Díaz
INVESTIGADOR PRINCIPAL
Daniel Morillo Giles
CENTRO INVESTIGADOR
MD Anderson Cancer Center Madrid
INVESTIGADOR PRINCIPAL
Adolfo De la Fuente Burguera
FECHA DE APERTURA
Marzo, 2026
FECHA DE CIERRE
,
CRITERIOS DE INCLUSIÓN
1. Age 18 years of age with life expectancy of 3 months.
10. For Cohort 1 only: Patient must be in a PR or PR-L and MRD+, must have detectable MRD as determined by the ClonoSEQ assay, actively taking zanubrutinib for at least 12 months, acceptable organ function (protocol-defined) at Screening within 28 days prior to Cycle 1 Day 1 (C1D1)
11. For Cohort 2 only: Relapsed disease (protocol-defined) for which patients are ineligible for or exhausted standard of care options; Actively taking zanubrutinib and with direct progression on zanubrutinib and no other anticancer therapy administered since; Acceptable organ function (protocol-defined) at Screening within 28 days prior to C1D1.
2. Eastern Cooperative Oncology Group Performance Status of 2;
3. Histopathologically confirmed diagnosis of CLL per the World Health Organization 2016 classification;
4. At least 1 criterion for measurable disease per iwCLL; creatine phosphokinase (CPK) < 2.5 × upper limit of normal (ULN);
5. Ability to tolerate contrast-enhanced computed tomography (CT) scan;
6. Ability to swallow/retain oral medications;
7. Negative serum pregnancy test in women of childbearing potential (WOCP);
8. WOCP and men who partner with WOCP must use highly effective contraceptive methods during study and 180 days after the last dose of study treatment;
9. Ability to understand/sign a written informed consent document.
10. For Cohort 1 only: Patient must be in a PR or PR-L and MRD+, must have detectable MRD as determined by the ClonoSEQ assay, actively taking zanubrutinib for at least 12 months, acceptable organ function (protocol-defined) at Screening within 28 days prior to Cycle 1 Day 1 (C1D1)
11. For Cohort 2 only: Relapsed disease (protocol-defined) for which patients are ineligible for or exhausted standard of care options; Actively taking zanubrutinib and with direct progression on zanubrutinib and no other anticancer therapy administered since; Acceptable organ function (protocol-defined) at Screening within 28 days prior to C1D1.
2. Eastern Cooperative Oncology Group Performance Status of 2;
3. Histopathologically confirmed diagnosis of CLL per the World Health Organization 2016 classification;
4. At least 1 criterion for measurable disease per iwCLL; creatine phosphokinase (CPK) < 2.5 × upper limit of normal (ULN);
5. Ability to tolerate contrast-enhanced computed tomography (CT) scan;
6. Ability to swallow/retain oral medications;
7. Negative serum pregnancy test in women of childbearing potential (WOCP);
8. WOCP and men who partner with WOCP must use highly effective contraceptive methods during study and 180 days after the last dose of study treatment;
9. Ability to understand/sign a written informed consent document.
CRITERIOS DE EXCLUSIÓN
1. Active second malignancy unless in remission with life expectancy > 2 years;
10. History of Stevens-Johnson syndrome or toxic epidermal necrolysis;
11. Intolerance to contrast-enhanced CT scan: Major surgery < 28 days prior to C1D1, minor surgery < 7 days prior to C1D1. Viral infections (protocol-defined);
12. Concomitant illness that would preclude safe participation in the study.
2. Active malignancy other than CLL requiring systemic therapy;
3. high-risk CLL TP53 mutations and 17P deletion;
4. History of Grade 3 rhabdomyolysis without complete recovery;
5. Prior chimeric antigen receptor-T cell therapy;
6. Prior investigational drugs within 28 days or 5 half-lives, whichever is shorter, prior to C1D1: allogeneic hematopoietic stem cell transplant (HSCT) within 60 days prior to C1D1, or clinically significant graft-versus-host disease (GVHD) requiring ongoing uptitration of immunosuppressive medications prior to Screening: Prior systemic anticancer treatment received within 21 days or 5 half-lives, whichever is shorter, prior to C1D1 (with the exception of zanubrutinib, which may be continued until the day before C1D1);
7. Receiving the following medications within 7 days or 5 half-lives, whichever is shorter, prior to C1D1: Medications that have a high risk of causing prolonged QT interval, corrected (QTc) and/or Torsades de Pointes, Peg-filgrastim or equivalent, St Johns Wort;
8. History of or ongoing drug-induced pneumonitis, History of stroke or intracranial hemorrhage within 6 months prior to C1D1, Requirement for anticoagulation with warfarin or equivalent vitamin K antagonists, including dual antiplatelet agents, within 5 half-lives of the anticoagulant or 7 days, whichever is longer, prior to C1D1;
9. Vaccinated with a live-attenuated vaccine within 4 weeks prior to C1D1: History of hypersensitivity or anaphylaxis to ema, approved BTKi, or any of their excipients;
10. History of Stevens-Johnson syndrome or toxic epidermal necrolysis;
11. Intolerance to contrast-enhanced CT scan: Major surgery < 28 days prior to C1D1, minor surgery < 7 days prior to C1D1. Viral infections (protocol-defined);
12. Concomitant illness that would preclude safe participation in the study.
2. Active malignancy other than CLL requiring systemic therapy;
3. high-risk CLL TP53 mutations and 17P deletion;
4. History of Grade 3 rhabdomyolysis without complete recovery;
5. Prior chimeric antigen receptor-T cell therapy;
6. Prior investigational drugs within 28 days or 5 half-lives, whichever is shorter, prior to C1D1: allogeneic hematopoietic stem cell transplant (HSCT) within 60 days prior to C1D1, or clinically significant graft-versus-host disease (GVHD) requiring ongoing uptitration of immunosuppressive medications prior to Screening: Prior systemic anticancer treatment received within 21 days or 5 half-lives, whichever is shorter, prior to C1D1 (with the exception of zanubrutinib, which may be continued until the day before C1D1);
7. Receiving the following medications within 7 days or 5 half-lives, whichever is shorter, prior to C1D1: Medications that have a high risk of causing prolonged QT interval, corrected (QTc) and/or Torsades de Pointes, Peg-filgrastim or equivalent, St Johns Wort;
8. History of or ongoing drug-induced pneumonitis, History of stroke or intracranial hemorrhage within 6 months prior to C1D1, Requirement for anticoagulation with warfarin or equivalent vitamin K antagonists, including dual antiplatelet agents, within 5 half-lives of the anticoagulant or 7 days, whichever is longer, prior to C1D1;
9. Vaccinated with a live-attenuated vaccine within 4 weeks prior to C1D1: History of hypersensitivity or anaphylaxis to ema, approved BTKi, or any of their excipients;
DESCRIPCIÓN
Cohort 1 and Cohort 2: Assess the anticancer activity of emavusertib in combination with zanubrutinib
PALABRAS CLAVE
antagonistas de la vitamin k, chronic leukemia, leukemia, lymphocytic, vitamin k antagonist
