临床试验/2024-516112-21-00

2024-516112-21-00招募中3 期

Myechild 01: International Randomised Phase III Clinical Trial in Children with Acute Myeloid Leukaemia - Incorporating an Embedded Dose Finding Study for Gemtuzumab Ozogamicin in Combination with Induction Chemotherapy

The University Of Birmingham29 个研究点分布在 2 个国家目标入组 289 人开始时间: 2024年12月2日最近更新: 2024年12月2日

试验速览

阶段: 3 期
状态: 招募中
发起方: The University Of Birmingham
入组人数: 289
试验地点: 29
主要终点: R1: Event-free survival (EFS) from date of randomisation 1 (R1)

研究概览入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

In newly diagnosed AML, high risk MDS (>10% blasts in the bone marrow) and isolated myeloid sarcoma:

Embedded dose finding studies

To establish the optimum tolerated number of 3 mg/m2 doses of gemtuzumab ozogamicin (up to a maximum of 3 doses) that can be safely delivered in combination with cytarabine plus mitoxantrone or liposomal daunorubicin in induction

Randomised

To compare mitoxantrone (anthracenedione) & cytarabine with liposomal daunorubicin (anthracycline) & cytarabine as induction therapy.
To compare a single dose of gemtuzumab ozogamicin 3 mg/m2 with the optimum tolerated number of doses of gemtuzumab ozogamicin (identified by the dose-finding study) when combined with induction chemotherapy
To compare two consolidation regimens: high dose cytarabine (HD Ara-C) and fludarabine & cytarabine (FLA) in standard risk patients.
To compare the toxicity and efficacy of two haemopoietic stem cell transplant (HSCT) conditioning regimens of different intensity: conventional myeloablaive conditioning (MAC) with busulfan/cyclophosphamide and reduced intensity conditioning (RIC) with fludarabine/busulfan.

研究设计

研究类型: Interventional

入排标准

年龄范围: 0 years 至 17 years（0-17 Years）
接受健康志愿者: 是

入选标准

•Trial Entry & R1 : A diagnosis of acute myeloid leukaemia (AML)/high risk myelodysplastic syndrome (MDS)(>10% blasts in the bone marrow)/isolated myeloid sarcoma(MS) (either de novo or secondary)
•Gemtuzumab ozogamicin not as part of DFS or R2: Normal renal function, defined as calculated creatinine clearance ≥90 ml/min/1.73m2
•Gemtuzumab ozogamicin not as part of DFS or R2: Normal hepatic function, defined as total bilirubin ≤2.5 upper limit of normal (ULN) for age and not due to leukaemic involvement or Gilbert’s syndrome or similar disorder
•Trial Entry & R1: Age <18 years at trial entry
•Gemtuzumab ozogamicin not as part of DFS or R2: ALT or AST ≤10 x ULN for age
•Gemtuzumab ozogamicin not as part of DFS or R2: Written informed consent from the patient and/or parent/legal guardian
•R2: Patient meets the inclusion criteria for Trial Entry & R1
•R2: Patient age: ≥12 months OR ≥12 weeks (once R2 open in patients aged ≥12 weeks and <12 months)
•R2: Normal renal function defined as calculated creatinine clearance ≥90ml/min/1.73m2
•R2: Normal hepatic function defined as total bilirubin ≤2.5 upper limit of normal (ULN) for age and not due to leukaemic involvement or Gilbert’s syndrome or similar disorder
•R2: ALT or AST ≤10 x ULN for age
•Dose Finding Study: Patient meets the inclusion criteria for Trial Entry & R1
•R2: Written informed consent from the patient and/or parent/legal guardian
•R3: Patient meets the inclusion criteria for Trial Entry & R1
•R3: Induction treatment as per MyeChild 01 protocol or treated with 2 courses of mitoxantrone & cytarabine off trial
•Trial Entry & R1: No prior chemotherapy or biological therapy for AML/high risk MDS/isolated MS other than that permitted in the protocol
•R3: MRD response: Patients with good risk cytogenetics/molecular genetics and a MRD level <0.1% by flow after course 2, or a decrease in transcript levels of >3 logs after course 2 for those with an informative molecular marker, but without an informative marker of sufficient sensitivity for flow MRD monitoring OR Patients with intermediate risk cytogenetics/molecular genetics with a MRD level <0.1% by flow after course 1 and course 2, or a decrease in transcript levels of >3 logs after course 1 and course 2 for those with an informative molecular marker, but without an informative marker of sufficient sensitivity for flow MRD monitoring
•R3: Written informed consent from the patient and/or parent/legal guardian
•R4: Patient meets the inclusion criteria for Trial Entry & R1
•R4: Induction treatment as per MyeChild 01 protocol or treated with 1 or 2 courses of mitoxantrone & cytarabine ± treatment intensification with FLA-Ida off trial
•R4: Patient is in CR or CRi defined as <5% blasts confirmed by flow cytometry/ molecular/FISH in a bone marrow aspirate taken within 6 weeks prior to randomisation to R4
•R4: Patient meets one of the following criteria and is a candidate for HSCT as per the protocol: High risk after course 1 (all patients with poor risk cytogenetics and patients with intermediate risk cytogenetics who fail to achieve CR/CRi) OR Intermediate risk cytogenetics with MRD >0.1% after course 1 and 2 measured by flow. If no flow MRD marker of sufficient sensitivity is identified, a molecular MRD marker with a sensitivity of >0.1% may be used OR Good risk cytogenetics with flow MRD >0.1% or a decrease in molecular MRD of <3 logs or rising transcript levels after course 3 despite treatment intensification (FLA-Ida) and after discussion with the Clinical Co-ordinators
•Dose Finding Study: Age: ≥12 months for the major dose finding study OR ≥ 12 weeks and <12 months for the minor dose finding study
•R4: Availability of a 9-10/10 HLA matched family or unrelated donor or 5-8/8 matched cord blood unit with an adequate cell dose as defined by the protocol section 17.1
•R4: Written informed consent from the patient and/or parent/legal guardian
•Trial Entry & R1: Normal cardiac function defined as fractional shortening ≥28% or ejection fraction ≥55%
•Trial Entry & R1: Fit for protocol chemotherapy
•Trial Entry & R1: Documented negative pregnancy test for female patients of childbearing potential
•Trial Entry & R1: Written informed consent from the patient and/or parent/legal guardian
•Trial Entry & R1: Patients with reproductive potential must agree to use effective contraception during the period of therapy. Both men and women of childbearing potential should be advised to use effective contraception to avoid pregnancy up to 12 months after the last dose of study treatment. Effective contraceptive methods include hormonal and barrier contraception etc.
•Dose Finding Study: Normal renal function defined as calculated creatinine clearance ≥90ml/min/1.73m2
•Dose Finding Study: Normal hepatic function defined as total bilirubin ≤2.5 upper limit of normal (ULN) for age unless it is caused by leukaemic involvement or Gilbert’s syndrome or similar disorder
•Dose Finding Study: ALT or AST ≤10 x ULN for age
•Dose Finding Study: Written informed consent from the patient and/or parent/legal guardian
•Gemtuzumab ozogamicin not as part of DFS or R2: Patient meets the inclusion criteria for Trial Entry & R1
•Gemtuzumab ozogamicin not as part of DFS or R2: Age: ≥12 months OR ≥ 12 weeks OR ≥28 days and <12 weeks (patients will receive a maximum of one dose of gemtuzumab ozogamicin)

排除标准

•Acute Promyelocytic Leukaemia
•Down Syndrome
•Blast crisis of chronic myeloid leukaemia
•Relapsed or refractory AML
•Bone marrow failure syndromes
•Prior anthracycline exposure which would inhibit the delivery of study anthracyclines
•Concurrent treatment or administration of any other experimental drug or with any other biological therapy for AML/high risk MDS/isolated MS
•Pregnant or lactating females

结局指标

主要结局

R1: Event-free survival (EFS) from date of randomisation 1 (R1)

Dose Finding Study: The incidence of dose limiting toxicities (DLTs)

R2: Event-free survival (EFS) from date of randomisation 2 (R2)

R3: Relapse-free survival (RFS) from date of randomisation 3 (R3)

R4: Early treatment related adverse reactions defined as the incidence by day 100 post-transplant of grade 3-5 toxicity for specific toxicities in the following systems using the National Cancer Institute (NCI) Common Terminology Criteria v4: Cardiac; Respiratory, thoracic and mediastinal; Gastrointestinal; Investigations; Renal and Urinary; Nervous system

R4: Relapse-free survival (RFS) from date of randomisation 4 (R4)

次要结局

Cumulative incidence of relapse (CIR) defined as time from first CR or CRi for patients entering at induction or from randomisation to the relevant question for patients entering at R3 or R4, to relapse
Dose Finding Study: The nature, incidence and severity of AEs evaluated until day 45 post course 1 and course 2
Dose Finding Study: Response measured by bone marrow morphology and MRD assessment post course 1 and 2
Complete Remission (CR) defined as CR or CRi and evaluated post course 1 and 2 of treatment (R1 and R2 only)
Reasons for failure to achieve CR evaluated pose course 1 and 2 of treatment and classified as resistant disease, induction death or not evaluable (R1 and R2 only)
Death in CR (DCR) defined as time from first CR or CRi for patients entering at induction or from randomisation to the relevant question for patients entering at R3 or R4, to date of death from any cause.
Event-free survival defined as time from randomisation to the relevant question to the first of failure to achieve CR (recorded as an event on day 1), relapse, secondary malignancy or death from any cause.
Overall Survival (OS) defined as time from randomisation to the relevant question to death from any cause or date last seen for patients who are alive at the end of the trial
Incidence of cardiotoxicity experienced within 10 years of randomisation and defined as a fall in fractional shortening to <28% or ejection fraction <55% (R1, R2 and R4 only)
Incidence of bilirubin of grade 3 or higher experienced within 30 days of end of trial treatment (R2 and R4 only)
Incidence of veno-occlusive disease experienced within 30 days of end of trial treatment (R2 and R4 only)
MRD negativity post course 1, course 2 and at the end of treatment (R1 and R2 only)
Time to haematological recovery defined as time from start of course to date of neutrophil recovery to 1.0 x 10^9/L and platelet recovery to 80 x 10^9/L for DFS patients; and neutrophil recover to 0.75 x 10^9/L and platelet recovery to 75 x 10^9/L for all other patients
Days in hospital per course of treatment
Incidence of mixed chimerism at day 100 post-transplant (R4 only)
Treatment Related Mortality (TRM) defined as the time bwtween randomisation to R4 and death which is unrelated to the underlying disease and considered related to the transplant procedure (R4 only)
Gonadal function at 1 year post-transplant and end of study follow up, assessed by Tanner stage, gonadotrophins and serum AMH (females)/inhibin B (males) (R4 only)

研究者

发起方

The University Of Birmingham

申办方类型

Educational Institution

责任方

Principal Investigator

主要研究者

Clinical Trial Coordinator

Scientific

The University Of Birmingham

研究点 (29)

Loading locations...

相似试验

已完成

不适用

DB289 Versus TMP-SMX para el tratamiento de la neumonia aguda neumocistis jiroveci (PCP)

PER-020-06IMMTECH INTERNACIONAL INC.,

进行中（未招募）

不适用

AI114373: A Phase III international, randomized, doubleblind, double-dummy study to evaluate the efficacy and safety of 300 mg or 600 mg of intravenous zanamivir twice daily compared to 75 mg of oral oseltamivir twice daily in the treatment of hospitalized adults and adolescents with influenza. - N/A

EUCTR2010-021621-12-NLGlaxoSmithKline Research & Development Ltd462

进行中（未招募）

不适用

A Study of Intravenous Zanamivir Versus Oral Oseltamivir in Adults and Adolescents Hospitalized With Influenza.hospitalised adults and adolescents with influenzaMedDRA version: 17.1Level: PTClassification code 10022000Term: InfluenzaSystem Organ Class: 10021881 - Infections and infestations

EUCTR2010-021621-12-BEGlaxoSmithKline Research & Development Ltd600

进行中（未招募）

1 期

EUCTR2010-021621-12-NOGlaxoSmithKline Research & Development Ltd626

进行中（未招募）

不适用

EUCTR2010-021621-12-SKGlaxoSmithKline Research & Development Ltd600