CTRI/2020/05/025367尚未招募3 期
Phase III Multicenter Open-Label Randomized Trial to Evaluate Efficacy and Safety of CPI-613® (devimistat) in Combination with High Dose Cytarabine and Mitoxantrone (CHAM) Compared to High Dose Cytarabine and Mitoxantrone (HAM) in Older Patients (≥ 50 years) with Relapsed/Refractory Acute Myeloid Leukemia (AML).
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 530
- 试验地点
- 6
- 主要终点
- CR
研究概览
简要总结
This is Phase III Multicenter Open-Label RandomizedTrial to Evaluate Efficacy and Safety of CPI-613® (devimistat) inCombination with High Dose Cytarabine and Mitoxantrone (CHAM) Compared to HighDose Cytarabine and Mitoxantrone (HAM) in Older Patients (≥ 50 years) withRelapsed/Refractory Acute Myeloid Leukemia (AML). Both Male and Female can be enrolled in the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 50.00 Year(s) 至 85.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Patient has provided an informed consent prior to initiation of any study specific activities/procedures.
- •2.Males and females age ≥ 50 years must have histologically documented AML that is relapsed from, or refractory to, prior standard therapies.
- •3.Refractory is defined as failure to achieve CR or CRi following a.
- •Two standard dose Cytarabine based induction cycles or one HiDAC based cycle or, b.
- •Persistent disease after one cycle of standard dose cytarabine (defined as no decrease in marrow blast percentage from diagnosis on Day 14 marrow) or, c.
- •Persistent disease after at least 2 cycles of a hypomethylating agent (azacytidine or decitabine) with or without venetoclax.
- •4.Relapse is defined as development of recurrent AML (as described by Döhner et al, 2017) after CR or CRi has been achieved with a prior chemotherapy or after disease progression on a hypomethylating agent with or without venetoclax.
- •5.ECOG PS 0-2 6.Expected survival greater than 3 months.
- •7.Women of child-bearing potential (i.e. women who are pre-menopausal or < 2 years post-menopausal or not surgically sterile) must practice a highly effective method of birth control consistent with local regulations regarding the use of birth control methods.
- •Examples are use of oral, injected or implanted hormonal methods of contraception, placement of an intra uterine device or intra uterine system, male partner sterilization, true abstinence during and for 6 months after the last administered dose of CHAM or HAM therapy and must have a negative serum pregnancy test within 1 week prior to treartment initiation and at first day of each cycle and at the end of systemic exposure.
- •(Note: Pregnant patients are excluded because the effects of CPI-613® (devimistat) on a fetus are unknown.
- •8.Fertile men who are sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control eg, either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository during the study period and up to 6 months after completion of the study screening, unless documentation of infertility exists 9.Good state of mental health, ability to understand and willingness to sign the informed consent form (ICF).
- •10.No radiotherapy, treatment with cytotoxic chemotherapy, treatment with biologic agents or any anti-cancer therapy within the 1 week prior to treatment with CPI-613® (devimistat).
- •Hydroxyurea and oral tyrosine kinase (FLT3) or Isocitrate Dehydrogenase 1 and 2 (IDH1/2) inhibitors being used with Grade ≤ 2 toxicity can be taken until the day prior to starting study therapy.
- •Previous exposure to a hypomethylating agent either alone or in combination with Venetoclax is allowed.
- •Patients must have fully recovered from the acute, non-hematological, non-infectious toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities with the exception of alopecia (returned to baseline status as noted before most recent treatment).
- •Patients with persisting, non-hematologic, non-infectious toxicities from prior treatment Grade ≤ 2 are eligible but must be documented as such 11.Laboratory values ≤ 2 weeks before dosing must be: a.
- •Adequate hepatic function (aspartate aminotransferase/serum glutamic-oxaloacetic transaminase [AST/SGOT] ≤ 5 x upper limit of normal [ULN], alanine aminotransferase/serum glutamic oxaloacetic transaminase [ALT/SGPT] ≤ 5 × ULN, bilirubin ≤ 1.5 × ULN).
- •Adequate renal function (serum creatinine clearance ≥ 60 mL/min per CockCroft-Gault formula).
- •Adequate coagulation (International Normalized Ratio [INR] must be < 1.7 unless on vitamin k antagonist anticoagulation).
- •12.Left Ventricular Ejection Fraction (LVEF) by Transthoracic Echocardiogram (TTE) or Multigated Acquisition Scan (MUGA) or cardiac Magnetic Resonance Imaging (MRI), sufficient to safely administer mitoxantrone.
- •Subjects must have an LVEF ≥ 45%.
- •13.No marked baseline prolongation of QT/QTc interval (repeated exhibition of a QTc interval >450 ms for male and > 470 ms for female patients).
- •14.No history of additional risk factors for torsade de pointes (e.g. clinically significant heart failure, hypokalemia, immediate family history of Long QT Syndrome).
- •15.Allow only patients who experienced relapse after 1 year from previous HiDAC treatment or who didn’t receive HiDAC previously (Note: This inclusion applies only to South Korea).
排除标准
- •1.Patients who have received cytotoxic chemotherapy treatment for their current relapsed or refractory AML.
- •(Treatment with hypomethylating agents (decitabine or azacytidine) either alone or in combination with venetoclax is allowed.
- •Targeted therapies including FLT3 or IDH1/2 inhibitors or Hydrea or venetoclax are allowed.
- •Targeted therapies and Hydrea may be taken until the day prior to starting CHAM or HAM therapy) .
- •2.Vulnerable adult and patient whose health conditions does not allow them to give their consent.
- •3.History or evidence of any other clinically significant disorder, condition or disease (e.g. symptomatic congestive heart failure, unstable angina pectoris, symptomatic myocardial infection, uncontrolled cardiac arrhythmia, pericardial disease or heart failure New York Heart Association Class III or IV), or severe debilitating pulmonary disease, that would potentially increase patients’ risk for toxicity and in the opinion of the Investigator, would pose a risk to patient safety or interfere with the study evaluation, procedures or completion.
- •4.Patients with active Central Nervous System (CNS) involvement (leukemic infiltration, blast in the spinal fluid).
- •5.Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g active peptic ulcer disease) bleeding diathesis (e.g. active peptic ulcer disease).
- •6.Female patients who are pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 6 months after the last dose of CHAM or HAM therapy (the teratogenic potential of CPI-613® (devimistat) is unknown).
- •Female patients of childbearing potential with a positive pregnancy test assessed by a serum pregnancy test at Screening.
- •7.Women of childbearing potential (i.e. women who are pre-menopausal or < 2 years postmenopausal or not surgically sterile) unwilling to practice a highly effective method of birth control consistent with local regulations regarding the use of birth control methods during treatment and for 6 months after completion of CHAM or HAM therapy for AML.
- •8.Male patients with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for 6 months after completion of CHAM or HAM therapy.
- •11.Life expectancy less than 3 months.
- •12.Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients.
- •13.Unwilling or unable to follow protocol requirements.
- •15.Patients with any amount of clinically significant pericardial effusion that requires drainage.
- •16.Evidence of ongoing, uncontrolled bacterial, viral or fungal infection.
- •17.Patients with known human immunodeficiency virus infection.
- •18.History of other malignancy within the past 5 years, with the following exception(s): a.
- •Malignancy treated with curative intent and with no known active disease present for ≥ 5 years before enrolment and felt to be at low risk for recurrence by the treating physician b.
- •Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of recurrent or residual disease c.
- •Adequately treated cervical carcinoma in situ without evidence of disease d.
- •Prostate cancer Stage 1 19.Patients receiving any other standard or investigational treatment for AML, or any other investigational agent for any indication within the past 1 week prior to initiation of CPI-613® (devimistat) treatment (the use of Hydrea and/or venetoclax, oral tyrosine kinase inhibitors FLT3 or IDH 1/2 inhibitors is allowed until the day prior to starting CHAM or HAM therapy.
- •Previous exposure to a hypomethylating agent either alone or in combination with venetoclax is allowed).
- •20.Patients who have received immunotherapy of any type within the past 1 week prior to initiation of CPI-613® (devimistat) treatment.
- •21.Requirement for immediate palliative treatment of any kind including minor surgery.
- •23.Patients who have had allogenic bone marrow transplantation within the last 6 months.
- •Patients who have had an allogenic transplant more than 6 months ago are eligible provided they have no graft vs host disease.
- •24.Cytarabine contraindications a.
- •Anemia, leucopenia and thrombocytopenia of non-malignant aetiology (e.g bone marrow aplasia); unless the clinician feels that such management offers the most hopeful alternative for the patient.
- •Degenerative and toxic encephalopathies, especially after the use of methotrexate or treatment with ionizing radiation.
- •25.Mitoxantrone contraindications a.
- •Mitoxantrone Sterile Concentrate is contraindicated in patients who have demonstrated prior hypersensitivity to mitoxantrone hydrochloride, other anthracyclines or any of its components.
- •Use in patients with profound bone marrow suppression is a relative contraindication depending on the clinical circumstances.
- •Mitoxantrone Sterile Concentrate should not be used during pregnancy or lactation.
结局指标
主要结局
CR
时间窗: a.1st Interim Analysis: 14 months after first randomization | b.2nd Interim Analysis: 25 months after first randomization | c.3rd Interim Analysis: 36 Months after first randomization
次要结局
- OS (Overall survival)(CR and CRh (Complete remission and Complete remission with partial hematologic recovery))
研究者
研究点 (6)
Loading locations...
相似试验
已完成
3 期
A Clinical Study To Evaluate Camrelizumab (SHR-1210) Plus Capecitabine and Oxaliplatin Followed by Sequential Treatment With Camrelizumab Plus Apatinib Mesylate in Advanced or Metastatic Gastric Cancer (GC) or Gastroesophageal Junction Cancer (GEJ) Without Prior Systemic TherapyGastroEsophageal CancerGastric CancerNCT03813784Jiangsu HengRui Medicine Co., Ltd.885
已完成
3 期
Study of Atezolizumab in Combination With Cabozantinib Versus Docetaxel in Patients With Metastatic Non-Small Cell Lung Cancer Previously Treated With an Anti-PD-L1/PD-1 Antibody and Platinum-Containing ChemotherapyCarcinoma, Non-Small-Cell LungNCT04471428Hoffmann-La Roche366
招募中
3 期
A Study of MRG003 in Combination With Pucotenlimab Versus Chemotherapy in the Treatment of Patients With Recurrent or Metastatic Nasopharyngeal CarcinomaNCT06976190Lepu Biopharma Co., Ltd.446
已完成
3 期
A Study of Atezolizumab in Combination With Carboplatin Plus (+) Nab-Paclitaxel Compared With Carboplatin+Nab-Paclitaxel in Participants With Stage IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC)Carcinoma, Non-Squamous Non-Small Cell LungNCT02367781Hoffmann-La Roche723
尚未招募
3 期
A Clinical study to compare effects and safety of Recombinant Human Thrombopoietin (rhTPO) Injection with Romiplostim injection in Indian Patients with Immune ThrombocytopeniaCTRI/2020/06/025707Eris Lifesciences Ltd108