EUCTR2020-002464-31-FR进行中（未招募）1 期
An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of KRT-232 in Combination with Acalabrutinib in Subjects with Relapsed/Refractory Diffuse Large B-cell Lymphoma or Relapsed/Refractory Chronic Lymphocytic Leukemia
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 85
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •1. Adults =18 years of age;
- •2. Patient population:
- •Cohort 1 (R/R DLBCL):
- •a) Histologically confirmed diagnosis of de novo TP53^wt ABC (non-GCB) or GCB DLBCL based on 2016 WHO Classification;
- •i) Phase 2: 25 or more subjects with non-GCB and 10 or more subjects with double-expressor lymphoma will be enrolled as described in Section 10.2 of the study protocol;
- •b) R/R DLBCL after treatment with at least 2 prior lines of systemic therapy or at least 1 prior line of systemic therapy in subjects who are ineligible for hematopoietic stem cell transplantation (autologous or allogeneic) for reasons other than active disease;
- •c) At least 1 measurable site of disease on computed tomography (CT) (defined as >1.5 cm in longest transverse diameter of a lesion [LDi]) and clearly measurable in 2 perpendicular dimensions);
- •Cohort 2 (R/R CLL):
- •d) Histologically confirmed diagnosis of TP53^wt CLL according to iwCLL criteria;
- •e) Previously treated with at least 1 prior regimen according to
- •current guidelines;
- •f) Active disease meeting at least 1 of the iwCLL 2008 criteria for
- •requiring treatment;
- •3. ECOG performance status of 0 to 2;
- •4. Adequate hematologic function independent of growth factor support for at least 7 days with the exception of pegylated G-CSF and darbepoetin which require at least 14 days, defined as:
- •a) Absolute neutrophil count (ANC) =1,000/mm^3;
- •b) Platelet count =50,000/mm^3;
- •5. Adequate hepatic function within 28 days prior to first dose defined as:
- •a) Total bilirubin within normal limits (WNL); if total bilirubin is > upper limit of normal (ULN) then patients are eligible if the direct bilirubin is =2.0 x ULN;
- •b) Aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine transaminase/serum glutamic pyruvic transaminase (ALT/SGPT) =2.5 ULN;
- •6. Adequate renal function within 28 days prior to the first dose defined as an estimated creatinine clearance =30 mL/min by Cockcroft Gault;
- •7. Female subjects of childbearing potential and their male partners, or male subjects who have female partners of childbearing potential must both use an effective contraception method during the study. In addition, both male and female subjects must continue to use contraception for 6 months after the last dose of study drug. Effective birth control for males includes either vasectomy or use of condoms. Effective birth control for females includes (a) combined estrogen- and progestogen-containing hormonal contraception (oral, intravaginal, transdermal); (b) intrauterine device combined with a barrier method; (c) intrauterine hormone-releasing system combined with a barrier method; (d) bilateral tubal occlusion or ligation; (e) vasectomized partner; and (f) sexual abstinence, when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
- •Note: Marketed drugs administered concomitantly in this study may have
- •different contraception requirements, including required duration of
- •contraception use. The contraception requirements in the prescribing
- •information (PI) or summary of product characteristics (SmPC) must be
- •followed for all concomitant drugs administered in this study.
- •Are the trial subjects under 18? no
- •Number of subjects for this age range:
- •F.1.2 Adults (18-64 years) yes
- •F.1.2.1 Number of subjects for this age range 34
- •F.1.3 Elderly (>=65 years) yes
- •F.1.3.1 Number of
排除标准
- •1. Subjects with a history of CNS involvement;
- •2. Any recent prior therapy meeting one or more of the following criter:
- •a) Concurrent anticancer treatment, such as chemotherapy, cytoreductive therapy, immune therapy, or cytokine therapy:
- •i) DLBCL: Within 14 days prior to the first dose of study treatment;
- •ii) CLL: Within 28 days prior to the first dose of study treatment;
- •b) Allogeneic stem cell transplant within the last 6 months, or active graft versus host disease following allogeneic transplant, or autologous stem cell transplant within 3 months prior to the first dose of study treatment;
- •c) Subjects who have received immunosuppressive therapy for graft-versus-host disease within 6 months prior to first dose of study treatment;
- •3. Subjects previously treated with MDM2 antagonist therapies;
- •4. Subjects previously treated with a BTK inhibitor;
- •5. Subjects with a history of bleeding diathesis or major hemorrhage within 6 months prior to first dose of study treatment;
- •6. History of stroke or intracranial hemorrhage within 6 months before first dose of study drug;
- •7. Uncontrolled intercurrent illness including but not limited to clinically significant cardiac disease (New York Heart Association Class III or IV); symptomatic congestive heart failure, unstable angina pectoris; unstable ventricular arrhythmia; or psychiatric illness/social situations that would limit compliance with study requirements;
- •8. Grade 2 or higher QTc prolongation (>480 milliseconds per National Cancer Institute Common Terminology of Adverse Events [v 5.0]);
- •9. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach; or extensive small bowel resection that is likely to affect absorption; symptomatic inflammatory bowel disease, or partial or complete bowel obstruction; or gastric restrictions and bariatric surgery, such as gastric bypass;#
- •10. Subjects with uncontrolled bacterial, fungal, parasitic, or viral infection. Subjects with acute bacterial infections requiring antibiotic use should not enroll until the infection is stable in the judgement of the treating physician; these subjects may be on antibiotics at time of enrollment;
- •11. Subjects with active hepatitis B virus (HBV) or hepatitis C virus (HCV);
- •12. Known history of HIV;
- •13. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, preprohormone) within 7 days of first dose of study drug;
- •14. Phase 1 only: Requires treatment with a strong and/or moderate CYP3A inhibitor/inducer within 7 days prior to first dose of study drug;
- •15. Phase 2 only: Requires treatment with a strong CYP3A inhibitor/inducer within 7 days prior to first dose of study drug;
- •16. Requires treatment with proton-pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects receiving proton-pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment to this study provided the proton pump inhibitor is discontinued at least 5 days prior to first dose of study drug;
- •17. Other malignancy within the last 3 years, other than curatively treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, organ-confined or treated nonmetastatic prostate cancer with normal prostate-specific antigen, in situ breast carcinoma after complete surgical resection, or superficial transitional cell bladder carcinoma;
- •18. Subjects who have had major surgery w
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