Share
Save
International Randomised Phase III Clinical Trial in Children With Acute Myeloid Leukaemia
The main purpose of this study is : 1. To establish which number of doses of gemtuzumab ozogamicin (up to a maximum of 3 doses) is tolerated and can be safety delivered in combination with cytarabine plus mitoxantrone or liposomal daunorubicin in induction 2. To compare mitoxantrone (anthracenedione) \& cytarabine with liposomal daunorubicin (anthracycline) \& cytarabine as induction therapy.
(Randomisation 1 (R1) closed early to recruitment on 8th September 2017, due to liposomal daunorubicin manufacturing issues resulting in unavailability of the drug. ) 3. To compare a single dose of gemtuzumab ozogamicin with the optimum tolerated number of doses of gemtuzumab ozogamicin (identified by the dose-finding study) when combined with induction chemotherapy.
4. To compare two consolidation regimens: high dose cytarabine (HD Ara-C) and fludarabine \& cytarabine (FLA) in standard risk patients. 5.
To compare the toxicity and effectiveness of two haemopoietic stem cell transplant (HSCT) conditioning regimens of different intensity: conventional myeloablative conditioning (MAC) with busulfan/cyclophosphamide and reduced intensity conditioning (RIC) with fludarabine/busulfan.
Study details:
MyeChild 01 is an international phase III clinical trial in children with acute myeloid leukaemia (AML); a disease with significant mortality. It will compare two induction chemotherapy regimens: mitoxantrone and cytarabine (current standard treatment) with liposomal daunorubicin and cytarabine. This will test liposomal daunorubicin, which is believed to be less cardiotoxic than similar conventional drugs, although this is unproven.
(Randomisation 1 (R1) closed early to recruitment on 8th September 2017, due to liposomal daunorubicin manufacturing issues resulting in unavailability of the drug. ). Patients responding well to induction chemotherapy are eligible for a randomisation of two consolidation regimens: high dose cytarabine (current standard treatment) or fludarabine and cytarabine (FLA); a regimen commonly used in patients with relapsed disease, testing whether FLA is more effective in front line therapy than standard consolidation treatment.
Patients with cytogenetic features associated with a higher risk of relapse and those responding sub-optimally to induction treatment are candidates for haemopoietic stem cell transplant (HSCT) and are eligible for a randomisation comparing two HSCT conditioning regimens: myeloablative conditioning (MAC) (current UNited Kingdom (UK) standard) or reduced intensity conditioning (RIC). HSCT has not consistently shown benefit in high risk patients because the mortality associated with the procedure has outweighed the advantage from a reduction in relapse risk. This will test whether reducing the intensity of conditioning improves survival by reducing transplant related deaths without increasing the relapse rate.
The trial incorporates a dose finding study for gemtuzumab ozogamicin. The aim is to identify the optimum tolerated number of doses of gemtuzumab ozogamicin (up to a total of 3 doses), which can be safely combined with either of the induction chemotherapy regimens and then to compare this number of doses with one dose of gemtuzumab ozogamicin. The intensity of treatment will be directed by cytogenetics/molecular genetics and response assessed by minimal residual disease (MRD) levels measured by flow cytometry and molecular methodology.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 0 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2016-04-01
Primary completion: 2031-12-01
Study completion finish: 2032-12-01
Study type
TREATMENT
Phase
PHASE3
Trial ID
NCT02724163
Intervention or treatment
DRUG: Gemtuzumab ozogamicin
DRUG: Liposomal daunorubicin
DRUG: Mitoxantrone
DRUG: Fludarabine
DRUG: Cytarabine
DRUG: Busulfan
DRUG: Cyclophosphamide
Conditions
- • Acute Myeloid Leukaemia
Find a site
Closest Location:
Perth Children's Hospital
Research sites nearby
Select from list below to view details:
Perth Children's Hospital
Perth, Not Specified, Australia
Sydney Children's Hospital
Sydney, Not Specified, Australia
Women and Children's Hospital Adelaide
Adelaide, Not Specified, Australia
Queensland Children's Hospital
Brisbane, Not Specified, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Participant Group/Arm | Intervention/Treatment |
---|---|
ACTIVE_COMPARATOR: Mitoxantrone
| DRUG: Mitoxantrone
|
EXPERIMENTAL: Liposomal daunorubicin
| DRUG: Liposomal daunorubicin
|
EXPERIMENTAL: Gemtuzumab Ozogamicin Dose Finding Study
| DRUG: Gemtuzumab ozogamicin
|
ACTIVE_COMPARATOR: High dose cytarabine
| DRUG: Cytarabine
|
EXPERIMENTAL: Fludarabine & cytarabine
| DRUG: Fludarabine
|
ACTIVE_COMPARATOR: Myeloablative conditioning
| DRUG: Busulfan
|
EXPERIMENTAL: Reduced intensity conditioning
| DRUG: Fludarabine
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
Incidence of dose limiting toxicities (DLTs). | Not Specified | Incidence of DLTs will be evaluated up to day 45 post course 1 and course 2 of induction chemotherapy. |
Event Free Survival (EFS). | The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. EFS estimates will be presented at 24 months along with 95% confidence intervals. | Event free survival (EFS) will be evaluated as the time from randomisation one to the first event, up to 16 years. |
Event Free Survival (EFS). | The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. EFS estimates will be presented at 24 months along with 95% confidence intervals. | Event free survival (EFS) will be evaluated as the time from randomisation two to the first event, up to 16 years.. |
Relapse free survival (RFS). | The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. RFS estimates will be presented at 24 months along with 95% confidence intervals. | Relapse free survival (RFS) will be evaluated as the time of randomisation three to the first relapse or death from any cause, up to 16 years. |
Early treatment related adverse reactions. | Early treatment related adverse reactions defined as the incidence by day 100 post-transplant of grade 3-5 toxicity for the following systems using the National Cancer Institute (NCI) Common Terminology Criteria v4: * Cardiac (pericardial effusion/Left ventricular systolic dysfunction). * Respiratory, thoracic and mediastinal (hypoxia/pneumonitis). * Gastrointestinal (GI) (diarrhoea/typhlitis/upper and lower GI haemorrhage). * Investigations (bilirubin). * Renal and Urinary (acute kidney injury/haematuria). * Nervous system (seizure). | Early treatment related adverse reactions will be evaluated at day 100 post-transplant. |
Relapse free survival (RFS). | The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. RFS estimates will be presented at 12 months along with 95% confidence intervals. | Relapse free survival (RFS) will be evaluated as the time of randomisation four to the first relapse or death from any cause, up to 16 years. |
Secondary outcome
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
---|---|---|
The nature, incidence and severity of adverse events (AEs) (gemtuzumab ozogamicin dose finding study). | Not Specified | Evaluated by day 45 post course 1 and course 2. |
Response measured by bone marrow assessment using morphology and minimal residual disease (MRD) assessment (gemtuzumab ozogamicin dose finding study). | Response is assessed by morphology confirmed by MRD levels measured by flow cytometry, molecular methods or fluorescence in situ hybridisation (FISH) as defined in the protocol, in combination with platelet and neutrophil counts. These results of these assessments will be combined to determine the patient's disease response using the response criteria defined in the protocol. | Evaluated by day 45 post course 1 and course 2. |
Serum pharmacokinetic (PK) parameters of gemtuzumab ozogamicin: Clearance (CL) (gemtuzumab ozogamicin dose finding study) | Serum PK parameters will be measured using serial samples taken at multiple timepoints during course 1 and at 1 month post first dose of gemtuzumab ozogamicin as defined in the protocol by dose cohort. | Evaluated up to one month after the first dose of gemtuzumab ozogamicin. |
Serum pharmacokinetic (PK) parameters of gemtuzumab ozogamicin: Volume of distribution (Vd) (gemtuzumab ozogamicin dose finding study) | Serum PK parameters will be measured using serial samples taken at multiple timepoints during course 1 and at 1 month post first dose of gemtuzumab ozogamicin as defined in the protocol by dose cohort. | Evaluated up to one month after the first dose of gemtuzumab ozogamicin. |
Complete remission (CR) (R1 & R2). | Evaluated using remission status at completion of course 1 and course 2. | Evaluated and presented at the completion of course 1 and 2 of treatment up to a maximum of 45 days post each course of treatment |
Reasons for failure to achieve CR (R1 & R2). | Evaluated as resistant disease, induction death or not evaluable.This will be evaluated at completion of course 1 and 2 of treatment, once patient's blood counts have recovered or reason for non-recovery has been determined. | Evaluated and presented at the completion of course 1 and 2 of treatment, up to a maximum of 45 days post each course of treatment. |
Cumulative Incidence of Relapse (CIR) (all randomisations). | The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. CIR estimates will be presented at 24 months along with 95% confidence intervals for randomisations 1, 2 and 3, and at 12 months for randomisation 4. | Evaluated as time from randomisation to the relevant question to relapse, up to 16 years. |
Death in CR (DCR) (R1, R2 & R3). | The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. DCR estimates will be presented at 24 months along with 95% confidence intervals. | Evaluated as time from randomisation to relevant question to date of death from any cause in patients who have achieved CR, up to 16 years. |
Event Free Survival (EFS) (R1, R2 & R3). | The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. EFS estimates will be presented at 24 months along with 95% confidence intervals. | Evaluated 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, up to 16 years. |
Overall Survival (OS) (all randomisations). | The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. OS estimates will be presented at 24 months along with 95% confidence intervals for randomisations 1, 2 and 3, and at 12 months for randomisation 4. | Evaluated 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, up to 16 years. |
Incidence of toxicities (all randomisations). | Not Specified | Evaluated 30 days after end of trial treatment. |
Incidence of cardiotoxicity (R1, R2 & R4 only). | Not Specified | Evaluated 30 days after end of trial treatment. |
Incidence of bilirubin of grade 3 of higher (R2 & R4 only). | Not Specified | Evaluated 30 days after end of trial treatment. |
Incidence of Veno-Occlusive Disease (R2 & R4 only). | Not Specified | Evaluated 30 days after end of trial treatment. |
Minimal Residual Disease (MRD) clearance after course 1 & 2 (R1 & R2 only). | Evaluated using MRD result at completion of course 1 and 2 once patient's blood counts have recovered or reason for non-recovery has been determined. | Evaluated and presented at completion of course 1 and 2 of treatment, up to a maximum of 45 days post each course of treatment. |
Time to haematological recovery (all randomisations). | Evaluated using the date of haematological recovery (platelets to \>=80 x 10\^9/L, and neutrophils to \>=1.0 x 10\^9/L). The primary analysis will be carried out once the last patient has a minimum of 1 year follow up. Time to haematological recovery estimates will be presented at 45 days post course 1 and course 2 of treatment along with 95% confidence intervals. | Evaluated by day 45 post course 1 and course 2. |
Days in hospital after each course of treatment (all randomisations). | Total number of days spent in hospital for each course of treatment, collected from date of randomisation until count recovery after final course of treatment, up to a maximum of 45 days post the final course of treatment. This will be summarised per course of treatment. | Evaluated once all patients have completed trial treatment. |
Incidence of mixed chimerism at day 100 post-transplant (R4 only). | Not Specified | Evaluated at day 100 post-transplant. |
Treatment Related Mortality (TRM) (R4 only). | The primary analysis will be carried out once the last patient has a minimum of 1 year follow up which is estimated to be 7 years after the start of recruitment. TRM estimates will be presented at 12 months along with 95% confidence intervals. | Evaluated as time in days between randomisation to R4 and death which is unrelated to the underlying disease and considered related to the transplant procedure. |
Gonadal function (R4 only). | The method of assessment will be by scale (Tanner scale) and physiological parameters. This will be evaluated at 1 year post-transplant and at the end of study follow-up. | Evaluated at 1 year post-transplant and at the end of follow-up, which is estimated to be through to study completion, an average timeframe of 10 years. |
Frequently Asked Questions
Please note: some questions and answers are submitted by anonymous patients or using AI, and have not been verified by Clinrol
No questions submitted. Be the first to ask a question!