ISRCTN10760016已完成2 期
A phase II study to determine the safety and efficacy of the dual mTORC inhibitor AZD2014 and to investigate additional toxicities in combination with rituximab in relapsed refractory DLBC
适应症
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 36
研究概览
简要总结
2019 Results article in https://www.ncbi.nlm.nih.gov/pubmed/31385336 results (added 13/08/2019)
研究设计
- 研究类型
- Interventional
入排标准
- 性别
- All
入选标准
- •1. Relapsed or refractory Diffuse Large B-Cell Lymphoma (DLBCL) relapsing after at least 1 course of potentially curative, anti-CD20 antibody containing regimen (e.g. RCHOP, GCHOP, RGCVP). High grade transformation from low grade lymphoma (e.g. follicular lymphoma, lymphoplasmacytic lymphoma, chronic lymphocytic leukaemia) is permitted. Patients must have relapsed post-ASCT or be considered not suitable for ASCT
- •2. Tissue biopsy (or bone marrow trephine if no other tissue available) confirming histology within 3 months of enrolment
- •3. Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses
- •4. Aged at least 18 years
- •5. Eastern Cooperative Oncology Group (ECOG) performance status of = 2
- •6. Females should be using adequate contraceptive measures (as described in the protocol, different for patient receiving rituximab), should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
- •6.1. Post-menopausal defined as amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
- •6.2. Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
- •7. Male patients should be willing to use barrier contraception (i.e. condoms) as described in the protocol, (different for patient receiving rituximab)
- •8. Ability to swallow and retain oral medication
- •9. CT measurable disease with at least 1 lesion having short axis = 1.5cm or splenomegaly = 13cm in cranio-caudal length attributable to relapsed lymphoma
- •10. Patients must have negative virology for HIV and hepatitis C prior to trial entry. Patients with an isolated anti-hepatitis B sAg antibody may be entered as this indicates previous vaccination. These patients MUST have HBV DNA tested
排除标准
- •1. Prior chemotherapy, biological therapy, radiation therapy, androgens, thalidomide, immunotherapy, other anti-cancer agents, and any investigational agents within 14 days of registration (not including palliative radiotherapy at focal sites). Corticosteroids are permitted during screening but should be weaned down to a max dose of prednisolone 10mg daily (or equivalent) by cycle 1 day 1
- •1.1. With the exception of alopecia, any unresolved toxicities from prior chemotherapy should be no greater than CTCAE (Version 4.0) Grade 2 at the time of registration
- •2. Major surgery within 4 weeks prior to entry to the study (excluding placement of vascular access), or minor surgery within 2 weeks of entry into the study
- •3. Exposure to potent or moderate inhibitors or inducers of CYP3A4/5 if taken within the stated washout periods before the first dose of study treatment
- •4. Exposure to potent or moderate inhibitors or inducers of CYP2C8 if taken within the stated washout periods before the first dose of study treatment
- •5. Exposure to sensitive or narrow therapeutic range substrates of the drug metabolising enzymes CYP2C8, CYP2C9, CYP2C19, CYP2D6 or the drug transporters Pgp (MDR1), BCRP, OATP1B1, OATP1B3, OCT1 and OCT2 within the appropriate wash-out period (minimum of 5x the reported terminal elimination half-life of each drug) before the 1st dose of study treatment
- •6. Previous treatment with any first generation mTORC1 inhibitors (rapamycin, sirolimus, temsirolimus, everolimus) or any dual mTORC1/2 inhibitors
- •7. Patients who have experienced intolerable AEs prejudged by the treating Investigator due to other mTORC1 or mTORC1/2 inhibitors, PI3 kinase inhibitors, or AKT inhibitors
- •8. Patients with proven central nervous system (CNS) involvement
- •9. As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases (e.g., severe hepatic impairment, interstitial lung disease (e.g.bilateral, diffuse, parenchymal lung disease), uncontrolled chronic renal diseases (e.g. glomerulonephritis, nephritic syndrome, Fanconi Syndrome or Renal tubular acidosis) or current unstable or uncompensated respiratory or cardiac conditions, or uncontrolled hypertension, active bleeding diatheses or active infection
- •10. Patients who have experienced any of the following procedures/conditions currently or in the preceding 12 months:
- •10.1. Coronary artery bypass graft
- •10.2. Angioplasty
- •10.3. Vascular stent
- •10.4. Myocardial infarction
- •10.5. Angina pectoris
- •10.6. Congestive heart failure New York Heart Association Grade =2
- •10.7. Ventricular arrhythmias requiring continuous therapy
- •10.8. Supraventricular arrhythmias including atrial fibrillation, which are uncontrolled
- •10.9. Haemorrhagic or thrombotic stroke, including transient ischaemic attacks or any other central nervous system bleeding
- •11. Abnormal echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) at baseline (left ventricular ejection fraction [LVEF] <50%)
- •12. Torsade’s de Pointes within 12 months of study entry
- •13. Mean (3 consequent ECGs 1 minute apart) resting QTcF or QTcB >470 msec as per local reading
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