Acute Myeloid Leukemia, ChildhoodPhase 3NCT03846362
A Prospective Multicenter Clinical Trial of MRD-based Treatment Strategy in Children and Young Adults With AML
A Phase 3 study testing HSCT in people with Acute Myeloid Leukemia, Childhood, run by Federal Research Institute of Pediatric Hematology, Oncology and Immunology at 2 sites in Russia.
Trial summary
Minimal-residual disease (MRD) will be measured either by flow cytometry, or polymerase chain reaction (PCR) methods, in 3 check-points and it will be one of the decision-making control parameter for the optimal therapy tactics. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Acute Myeloid Leukemia, Childhood
- What is being tested?
- HSCT
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 500 participants
- Where
- 2 sitesRussia
- Study dates
- 1 Apr 2019to Jan 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- de novo acute myeloid leukemia
- signed informed consent
Who cannot join
- diagnosis of: Fanconi anemia, acute promyelocytic leukemia, MDS, JMML, AML as secondary malignancy, Dawn syndrome.
Trial locations and contacts
2 sites in 1 country.
Russia2 sites, 2 recruiting
- Recruiting
Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology
Moscow, 117198
Irina Kalinina, 84956647078 ext. 7432, oml-registration@fnkc.ru
Zhanna Shekhovtsova, 84956647078, zhanna.shekhovtsova@fccho-moscow.ru
- Not yet recruiting
Regional Children's Clinical Hospital № 1
Yekaterinburg, Sverdlovsk Oblast, 620149
Oleg Arakaev, (343) 231-91-09
Larisa Fechina, PhD
About this study
Official title: A Prospective Multicenter Clinical Trial of Treatment Strategy Based on MRD Level After 2 Initial Courses of Chemotherapy in Children and Young Adults With Acute Myeloid Leukemia
Minimal-residual disease (MRD) will be measured either by flow cytometry, or polymerase chain reaction (PCR) methods, in 3 check-points and it will be one of the decision-making control parameter for the optimal therapy tactics.
Patients with initially high-risk group and those with high MRD after 2 initial courses of chemotherapy will be assigned to the allogenic transplantation of the hematopoietic stem cells from Human Leucocyte Antigen (HLA) matched or haploidentical family donors.
Read the detailed description
Genetic alterations in acute myeloid leukemia (AML) clone are well known prognostic risk factors of AML relapse. Standard risk group includes favorable t (15;17) (q22; q21) and inv (16)/t (16;16). High-risk patients have a complex karyotype rearrangement (3 and more), inversion of the long arm in 3rd chromosome and EVI1 gene rearrangement, monosomy 5 and 7, translocations involving KMT2A gene and several rare translocations. All other genotype alterations attributed to the moderate risk group.
Besides genetic factors, detection of the minimal residual disease (MRD) after initial chemotherapy and its decrease rate after 1st postremission chemotherapy with high dose Cytarabine and anthracyclines, plays a crucial role in the development of the morphologic relapse. Patients with PCR-MRD<0,1% after 2 courses of chemotherapy have a 30% or less risk of relapse, while PCR-MRD>0,1% - over 70%. In the clinical trial investigators are planning to measure MRD either by immune-phenotype, or PCR methods, in 3 check-points and it will be one of decision-making control parameter for the optimal therapy tactics.
Patients with initially high-risk group and those with high MRD after 2 initial courses of chemotherapy will be assigned to the allogenic transplantation of the hematopoietic stem cells from HLA- matched or haploidentical family donors.
- Conditions
- Acute Myeloid Leukemia, Childhood
- Being tested
- HSCT
- Keywords
- AML, MRD, stem cell transplantation, pediatric, leukemia, haploidentical, TcRab-depletion, young adult
- Medical subject headings
- Leukemia, Myeloid, Acute, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HSCTOther
allogenic HSCT from 5-8 HLA-MM family donor as a first choice for patients with initial high risk of relapse and for patients with MRD2>0,1% and initial intermediate risk
| Study group | Role | What they receive |
|---|---|---|
| intermediate risk MRD2>0,1% | Experimental | MRD2>0,1% - FLA - MRD3 - HSCT Receives: Other: HSCT |
What is being measured
The primary outcome is the main question the study is designed to answer.
relapse-free survival (RFS)
relapse-free survival from date of diagnosis till date of relapse, or date of death (whichever comes first) or date of last follow up
Measured: 1 year
Secondary outcomes (11)
overall survival (OS)
Measured: 1 year
event-free survival (EFS)
Event=relapse/nonresponse, death or second malignancy
Measured: 2 years
The proportion of of patients with severe adverse effects
The proportion of of patients with severe adverse effects of therapy according to CTCAE (ver 4.3)
Measured: 6 months
The proportion of of patients with severe infections
The proportion of of patients with severe infections: number of episodes, grade, after each course of chemotherapy
Measured: 1 month
The proportion of of patients with severe cardiotoxicity
The proportion of of patients with severe cardiotoxicity: number of episodes and %EF by echocardiogam
Measured: 1 year
MRD dynamic
MRD (IFT and/or PCR) dynamic between check-points
Measured: 1 months
MRD specificity and sensitivity
MRD specificity and sensitivity in relapse prognosis
Measured: 1, 2, 3 months
Cumulative incidence of relapse
competing event - death in CR
Measured: 6 months, 1 year
Cumulative incidence of transplant-related mortality
for transplanted patients
Measured: 6 months after HSCT
Cumulative incidence of aGvHD II-IV grade
for transplanted patients
Measured: 100 days after HSCT
Cumulative incidence of cGvHD
for transplanted patients
Measured: 1 year after HSCT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2019
- Study start1 Apr 2019
- Primary completionDec 2023 (estimated)
- Study completionJan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid Leukemia, ChildhoodStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Federal Research Institute of Pediatric Hematology, Oncology and Immunology
- Sponsor type
- University, hospital or other
- Collaborators
- Physicians, Innovations, Science for Children Fund
- Responsible party
- Sponsor
- Investigators
- Alexey Maschan, Principal investigator, National Research Center for Pediatric Hematology , Moscow, Russian FederationMichael Maschan, Study director, National Research Center for Pediatric Hematology , Moscow, Russian FederationGalina Novichkova, Study chair, National Research Center for Pediatric Hematology , Moscow, Russian Federation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03846362
- Sponsor's protocol ID
- NCPHOI-2018-05
- Status last verified
- Mar 2023
- First submitted
- 14 Feb 2019
- Last updated
- 16 Mar 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Multicenter Clinical Trial of Treatment Strategy Based on MRD Level After 2 Initial Courses of Chemotherapy in Children and Young Adults With Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT03846362
- Acronym / sponsor ID
- NCPHOI-2018-05
- Conditions
- Acute Myeloid Leukemia, Childhood
- Keywords
- AML, MRD, stem cell transplantation, pediatric, leukemia, haploidentical, TcRab-depletion, young adult
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Federal Research Institute of Pediatric Hematology, Oncology and ImmunologyUniversity, hospital or other
- Collaborators
- Physicians, Innovations, Science for Children Fund
- Study start
- 1 Apr 2019 (actual)
- Primary completion
- Dec 2023 (estimated)
- Study completion
- Jan 2025 (estimated)
- First posted
- 19 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Minimal-residual disease (MRD) will be measured either by flow cytometry, or polymerase chain reaction (PCR) methods, in 3 check-points and it will be one of the decision-making control parameter for the optimal therapy tactics.
Patients with initially high-risk group and those with high MRD after 2 initial courses of chemotherapy will be assigned to the allogenic transplantation of the hematopoietic stem cells from Human Leucocyte Antigen (HLA) matched or haploidentical family donors.
Detailed description
Genetic alterations in acute myeloid leukemia (AML) clone are well known prognostic risk factors of AML relapse. Standard risk group includes favorable t (15;17) (q22; q21) and inv (16)/t (16;16). High-risk patients have a complex karyotype rearrangement (3 and more), inversion of the long arm in 3rd chromosome and EVI1 gene rearrangement, monosomy 5 and 7, translocations involving KMT2A gene and several rare translocations. All other genotype alterations attributed to the moderate risk group.
Besides genetic factors, detection of the minimal residual disease (MRD) after initial chemotherapy and its decrease rate after 1st postremission chemotherapy with high dose Cytarabine and anthracyclines, plays a crucial role in the development of the morphologic relapse. Patients with PCR-MRD<0,1% after 2 courses of chemotherapy have a 30% or less risk of relapse, while PCR-MRD>0,1% - over 70%. In the clinical trial investigators are planning to measure MRD either by immune-phenotype, or PCR methods, in 3 check-points and it will be one of decision-making control parameter for the optimal therapy tactics.
Patients with initially high-risk group and those with high MRD after 2 initial courses of chemotherapy will be assigned to the allogenic transplantation of the hematopoietic stem cells from HLA- matched or haploidentical family donors.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| intermediate risk MRD2>0,1% | Experimental | Other: HSCTMRD2>0,1% - FLA - MRD3 - HSCT |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- de novo acute myeloid leukemia
- signed informed consent
Key exclusion criteria (1 listed)
- diagnosis of: Fanconi anemia, acute promyelocytic leukemia, MDS, JMML, AML as secondary malignancy, Dawn syndrome.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HSCTallogenic HSCT from 5-8 HLA-MM family donor as a first choice for patients with initial high risk of relapse and for patients with MRD2>0,1% and initial intermediate risk | Other | intermediate risk MRD2>0,1% |
Primary outcome
relapse-free survival (RFS)
Time frame: 1 year
relapse-free survival from date of diagnosis till date of relapse, or date of death (whichever comes first) or date of last follow up
11 secondary outcomes
overall survival (OS)
Time frame: 1 year
event-free survival (EFS)
Time frame: 2 years
The proportion of of patients with severe adverse effects
Time frame: 6 months
The proportion of of patients with severe infections
Time frame: 1 month
The proportion of of patients with severe cardiotoxicity
Time frame: 1 year
MRD dynamic
Time frame: 1 months
MRD specificity and sensitivity
Time frame: 1, 2, 3 months
Cumulative incidence of relapse
Time frame: 6 months, 1 year
Cumulative incidence of transplant-related mortality
Time frame: 6 months after HSCT
Cumulative incidence of aGvHD II-IV grade
Time frame: 100 days after HSCT
Cumulative incidence of cGvHD
Time frame: 1 year after HSCT
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alexey Maschan principal investigator
National Research Center for Pediatric Hematology , Moscow, Russian Federation
Michael Maschan study director
National Research Center for Pediatric Hematology , Moscow, Russian Federation
Galina Novichkova study chair
National Research Center for Pediatric Hematology , Moscow, Russian Federation
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing HSCT in people with Acute Myeloid Leukemia, Childhood, run by Federal Research Institute of Pediatric Hematology, Oncology and Immunology at 2 sites in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Irina Kalinina (+7 495 287 65 70 ext. 7425, oml-registration@fnkc.ru), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
relapse-free survival (RFS) (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2023.