2024-513084-38-00招募中2 期
SALMA Study - Phase I/II Clinical Trial Assessing the Combination of Sulfasalazine with Standard of Care Induction Therapy in Newly Diagnosed Non-Favorable Acute Myeloid Leukemias (AML) Patients 60 years or older
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 64
- 试验地点
- 10
- 主要终点
- Phase I : Documentation during the dose escalation of dose limiting toxicity (DLT)
研究概览
简要总结
Phase I To assess the safety, characterize the dose-limiting toxicities (DLTs), and identify the maximal tolerated dose (MTD), and recommended phase II dose (RP2D) of the combination of Sulfasalazine (SSZ) with Idarubicin (IDA) and Cytarabine (AraC) in patients with newly diagnosed non-favorable AML. Probability of DLT should not exceed 33% at the end of the induction cycle (EOI) of IDA-AraC + SSZ treatment (up to Day 42). Phase II To assess preliminarily the anti-leukemia efficacy of the combination of IDA-AraC + SSZ, mainly in phase II, in newly diagnosed non-favorable AML with reference from historical data on complete remission rate, and MRD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Patients aged 60 years or older
- •With newly diagnosed AML (short course treatment with hydroxyurea and or steroids is acceptable). Patients with AML secondary to an antecedent Myelodysplastic Syndromes (MDS) or Myeloproliferative Neoplasms (MPN) are eligible, as those with therapy-related AML.
- •Eligible for intensive chemotherapy in the investigator’s opinion
- •Multiparameter Flow Cytometry detected at screening allowing and / or compatible with MFCM-based MRD monitoring defined according to ELN criteria (Phase II only)
- •ECOG performance status ≤2
- •AST and ALT ≤3.0 x upper the limit of normal (ULN) and total and direct serum bilirubin ≤ 1.5 x ULN unless considered due to leukemia
- •Estimated glomerular filtration rate (GFR) ≥ 50 mL/min according to the MDRD equation
- •Written informed consent obtained prior to any screening procedures
- •Eligible for National Health Insurance in France.
排除标准
- •Myeloid Sarcoma with < 20% bone marrow blasts
- •History of allergic reaction to idarubicin or idarubicin excipients
- •History of allergic reaction to cytarabine or cytarabine excipients
- •Known glucose 6-phosphate dehydrogenase deficiency
- •Known acute intermittent porphyria or porphyria variegata
- •Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate treatment).
- •Other uncontrolled or active malignant disease within prior 12 months (excluding myelodysplastic syndrome; cutaneous basal cell carcinoma, “in-situ” carcinoma of the cervix or breast, or other local malignancy excised).
- •Known human immunodeficiency virus (HIV) infection or HIV-related malignancy
- •Clinically active hepatitis B or hepatitis C infection
- •Inability to swallow
- •Known malabsorption syndrome or other condition that may significantly impair absorption of oral study medications
- •Patient who has received a vaccine injection with live-attenuated virus in the last three weeks
- •Participation in another therapeutic interventional clinical study within 30 days of enrolment
- •Administration of any therapy considered investigational (i.e., used for non-approved indications(s) or in the context of a research investigation) within 5 drug half-lives (whichever is longer) prior to the first dose of study drug
- •Previous treatment by anthracyclines
- •Any contraindication to use anthracyclines including uncontrolled coronary disease, severe renal failure, severe hepatic failure, recent myocardial infarction, symptomatic congestive heart failure, severe cardiomyopathy, significant arrhythmia as estimated by the investigator or LVEF <53% as assessed by echocardiography or MUGA, anterior treatment by idarubicin and/or anthracyclines and anthracènediones beyond the maximum cumulative dose
- •Any contraindication to use cytarabine including degenerative and toxic encephalopathy
- •Any condition requiring treatment with digoxin
- •Any of concurrent severe and/or uncontrolled medical condition, which could compromise participation in the study
- •Females who are pregnant or breastfeeding
- •In a man whose sexual partner is a woman of childbearing potential, unwillingness or inability of the man or woman to use a highly effective contraceptive method for the entire treatment period and for at least 6 months after completion of protocol treatment. Highly effective contraception methods include: combined (estrogen and progestogen containing) hormonal methods associated with inhibition of ovulation, intra-uterine device; surgical sterilization (including bilateral tubal occlusion, partner’s vasectomy) or sexual abstinence if this is the preferred and usual lifestyle of the patient. Male patients must not freeze or donate sperm starting at screening and throughout the treatment period and 3 months after the administration of the final dose of study medication.
- •In a heterosexually active woman of childbearing potential, unwillingness or inability to use a highly effective contraceptive method (as described above) for the entire treatment period and for at least 6 months after the administration of the final dose of study medication. Women are not regarded as of childbearing potential if they are post-menopausal (at least 2 years without menses) or are surgically sterile (at least 1 month before enrollment). Female patients must not donate or retrieve, for their own use, ova from the time of screening and throughout the treatment period, and for 12 weeks after the administration of the final dose of study medication. Female patients must agree not to breastfeed from the time of screening and throughout the protocol period, and for (5 1/2 lives) days after the administration of the final dose of study medication.
- •Proven central nervous system leukemic involvement
- •Adults subjects to a legal protection order or unable to give their consent
- •Persons deprived of their freedom by judicial or administrative decision, person hospitalized without their consent by virtues of articles L 3212-1 and L3213-1 and who are not subject to the provisions of article L 1121
- •Favorable risk cytogenetics: t(15;17), t(8;21), inv(16) or t(16;16) or presence of PML-RARA, RUNX1-RUNX1T1 or CBFB-MYH11 fusion transcript
- •Presence of FLT3-ITD or TKD mandating treatment with midostaurin.
- •Concurrent therapy with any cytotoxic drug within 3 weeks before the first study dose. Only hydroxyurea for the control of blood counts is permitted
- •Patients planned to received CPX-351 for myelodysplasia-related changes or therapy-related AML
- •Previous treatment with sulfasalazine in the last 5 years or ongoing treatment with sulfasalazine or 5-aminosalicylic acid (5-ASA) for ulcerative colitis or inflammatory rheumatisms.
- •History of allergy SSZ, one of its metabolites (5-aminosalicylic acid, 5-ASA) or mesalazine, other sulfonylarylamines sulfonamides or salicylates, or sulfasalazine excipients
结局指标
主要结局
Phase I : Documentation during the dose escalation of dose limiting toxicity (DLT)
Phase I : Documentation during the dose escalation of dose limiting toxicity (DLT)
Phase I : Identification of a maximal tolerated dose (MTD) anticipated to be the recommended phase II dose (RP2D) - MTD is defined by a target DLT rate of 33%, assessed during the dose escalation phase by a continual reassessment method - RP2D is anticipated to be the MTD. However, it could be equal to one dose level lower than the MTD. It will be determined in interaction with the DSMB, insofar that this dose level is validated by PK/PD studies and efficacy preliminary data.
Phase I : Identification of a maximal tolerated dose (MTD) anticipated to be the recommended phase II dose (RP2D) - MTD is defined by a target DLT rate of 33%, assessed during the dose escalation phase by a continual reassessment method - RP2D is anticipated to be the MTD. However, it could be equal to one dose level lower than the MTD. It will be determined in interaction with the DSMB, insofar that this dose level is validated by PK/PD studies and efficacy preliminary data.
Phase II : MRD-negative Complete Response at EOI (day 28-42) per ELN 2022 Criteria
Phase II : MRD-negative Complete Response at EOI (day 28-42) per ELN 2022 Criteria
次要结局
- Assessment of safety - Safety outcome measures will be assessed continuously during the study. Monitoring of ECGs and clinical laboratory values are integral to safety assessment. Adverse events (AE), treatment emergent adverse events (TEAE) and treatment-related TEAEs will be evaluated according to the NCI CTCAE version 5.0.
- Pharmacokinetics - To assess SSZ and its metabolites, IDA (and its metabolite) and AraC. This will allow to determine a PK model for SSZ at an early and late time point and confirm the lack of interaction between SSZ and IDA or AraC.
- Pharmacodynamics - Pharmacodynamic assays aim at demonstrating ROS induction upon SSZ exposure relative to pre-treatment levels.
- Antileukemia activity - Response at EOI assessment (day 28-42) per ELN 2022 Criteria.
- Antileukemia activity - Survival assessment at 12 months
研究者
Raphael Itzykson
Scientific
Assistance Publique Hopitaux De Paris
研究点 (10)
Loading locations...
相似试验
终止
不适用
CAR-T Cells Therapy in Relapsed/Refractory Acute Myeloid LeukemiaRelapsed/Refractory Acute Myeloid Leukemia(AML)NCT03473457Zhujiang Hospital2
进行中（未招募）
2 期
Efficacy of HAD Induction With Intensified Cytarabine in Newly-diagnosed CEBPA Double Mutated Acute Myeloid LeukemiaCEBPA Double MutationAcute Myeloid LeukemiaNCT04415008Institute of Hematology & Blood Diseases Hospital, China61
Unknown
1 期
Decitabine Combined With Unrelated Cord Blood Transplantation for Elderly Patients With AMLAcute Myeloid LeukemiaNCT03913312Ruijin Hospital150
Unknown
2 期
A Phase 2 Study of Venetoclax in Combination With Low-dose HHT, G-CSF, and AZA as First-line Treatment for Newly Diagnosed Elderly AML Patients Unfit for Intensive ChemotherapyLeukemia, Myeloid, AcuteNCT04824924Shanghai Jiao Tong University School of Medicine100
招募中
1 期
A Phase Ib Study of APG-115 Single Agent or in Combination With Azacitidine or Cytarabine in Patients With AML and MDS.Acute Myeloid Leukemia (AML)Myelodysplastic Syndromes (MDS)NCT04275518Ascentage Pharma Group Inc.102