A Randomized, Double-Blind Phase 3 Study of Ibrutinib in Combination With Corticosteroids versus Placebo in Combination With Corticosteroids in Subjects with New Onset Chronic Graft Versus Host Disease (cGVHD)

Pharmacyclics LLC0 个研究点目标入组 193 人开始时间: 2017年3月2日最近更新: 2022年3月2日

适应症

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: Pharmacyclics LLC
入组人数: 193

研究概览入排标准研究者记录与标识符相似试验

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

•Prior to randomization, each potential subject must satisfy all of the following inclusion criteria.
•Disease related
•1. New onset moderate or severe cGVHD as defined by the NIH Consensus Development Project Criteria (2014, see Appendix M, Appendix N and Appendix O of protocol).
•2. History of an allogeneic hematopoietic cell transplant.
•3. Need for systemic treatment with corticosteroids for cGVHD.
•4. No previous systemic treatment for cGVHD (including extracorporeal photopheresis [ECP]).
•5. Participants may be receiving other immunosuppressants for the prophylaxis or treatment of acute GVHD but if the subject is receiving prednisone for prophylaxis or treatment of acute GVHD it must be at or below 0.5 mg/kg/d.
•6. Participants may have received pre-transplant BTK inhibitors for other reasons besides cGVHD such as for the treatment of leukemia or lymphoma, but must not have received a BTK inhibitor since the time of transplant.
•Demographic
•7. Age =12 years old.
•8. Karnofsky or Lansky (subjects <16 years) performance score =60.
•9. Adequate renal function defined as estimated Creatinine Clearance =30 mL/min (Cockcroft-Gault formula)
•10. Adequate hepatic function as defined by:
•- Total bilirubin =1.5 x ULN (unless of non-hepatic origin or due to Gilbert’s Syndrome) or
•- Total bilirubin of > 1.5 x ULN to 3.0 x ULN if due to GVHD
•11. Adequate hematological function defined as:
•- Absolute neutrophil count =1.0 x 109/L and off growth factor support for 7 days
•- Platelets =30 x 109/L and no transfusion for 7 days
•12. PT/INR <1.5 x ULN and PTT (aPTT) <1.5 x ULN (unless abnormalities are unrelated to coagulopathy or bleeding disorder). When treated with warfarin or other vitamin K antagonist, then INR =3.0 (Section 6.2.3 of protocol)
•Ethical/Other
•13. Male and female subjects of reproductive potential who agree to use both a highly effective methods of birth control (eg, implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], complete abstinence, or sterilized partner) and a barrier method (eg, condoms, cervical ring, sponge, etc) during the period of therapy and for 90 days for both females and males after the last dose of study drug.
•Are the trial subjects under 18? yes
•Number of subjects for this age range: 35
•F.1.2 Adults (18-64 years) yes
•F.1.2.1 Number of subjects for this age range 151
•F.1.3 Elderly (>=65 years) no
•F.1.3.1 Number of subjects for this age range

排除标准

•To be enrolled in the study, potential subjects must meet NONE of the following exclusion criteria:
•Disease related
•1. Received any previous systemic treatment for cGVHD with the following exception
•- Corticosteroids for cGVHD received within the 72 hours prior to signing the informed consent form.
•2. Inability to begin a prednisone dose =0.5 mg/kg/d for the treatment of cGVHD.
•3. Presence of single-organ, genito-urinary involvement with cGVHD as the only manifestation of cGVHD.
•Concurrent conditions
•4. Received any investigational agent =28 days before randomization.
•5. Received donor lymphocyte infusion (DLI) =56 days before randomization.
•6. Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization.
•7. Any uncontrolled active systemic infection or active infection requiring systemic treatment that was ongoing =7 days before randomization. This does not include secondary prophylaxis of well controlled fungal infections, ongoing treatment of controlled viral reactivations (eg, CMV), or treatment or prophylaxis of controlled low grade central line infections (eg, Staphylococcus epidermidis).
•8. Progressive underlying malignant disease or active post-transplant lymphoproliferative disease.
•9. History of other malignancy (not including the underlying malignancy that was the indication for transplant), with the following exceptions:
•- Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to Screening and felt to be at low risk for recurrence by treating physician
•- Adequately treated nonmelanomatous skin cancer or lentigo maligna melanoma without current evidence of disease
•- Adequately treated cervical carcinoma in situ without current evidence of disease
•10. Subject has a concurrent illness which in the opinion of the investigator may interfere with the treatment and evaluation of the subject.
•11. Known bleeding disorders (eg, von Willebrand’s disease or hemophilia).
•12. History of stroke or intracranial hemorrhage within 6 months prior to randomization.
•13. Known history of human immunodeficiency virus (HIV).
•14. Subject with chronic liver disease with hepatic impairment per Child-Pugh classification Class C (Appendix E). Please note that acute liver dysfunction due to cGVHD is not applicable to the evaluation of Child-Pugh classification.
•15. Active hepatitis C virus (HCV) or hepatitis B virus (HBV). Subjects who are positive for hepatitis B core antibody or hepatitis B surface antigen or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result before randomization. Those who are PCR positive will be excluded.
•16. Vaccinated with live, attenuated vaccines within 4 weeks of randomization.
•17. Major surgery within 4 weeks of randomization.
•18. Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator’s opinion, could compromise the subject’s safety or put the study outcomes at undue risk.
•19. Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or

研究者

发起方

Pharmacyclics LLC

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