NOPHO-DBH AML 2012 Protocol: Research study for treatment of children and adolescents with acute myeloid leukemia 0-18 years

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vaestra Goetalandsregionen

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

1 Mar 2013 → ongoing

Decision date (initial)

2024-11-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-518254-16-00

EudraCT number

2012-002934-35

ClinicalTrials.gov

NCT01828489

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

The AML 2012 study is a treatment and research protocol with the overall aim of improving prognosis for children and adolescents with AML. This is to be achieved by better risk stratification based on MRD quantification and more intensive induction compared to previous NOPHO protocols.

Specific research aims are 1) To investigate if DaunoXome® has a higher efficacy than Mitoxantrone, when given in course 1 for treatment of pediatric AML

2) To investigate if FLADx has a higher efficacy than ADxE when given as the second induction course for treatment of pediatric AML

3) To investigate the correlation between MRD measurement by PCR and flow cytometry and the prognostic impact of MRD with either method after course 1 and 2 respectively.

Secondary objectives 5

1. Improving both EFS and OS as compared to NOPHO-AML 93 and 2004.
2. Improving EFS and OS for patients with intermediate response (5- 14.9%) blasts after course 1 and patients with t(8;21).
3. Achieving improved anti-leukaemic effect with no increase or a decrease in early toxic deaths and deaths in CR.
4. Comparing outcome in subgroups of patients as defined by characteristics of both patients and disease such as age, FAB type and cytogenetics (e.g. t(8;21, inv(16) and MLL rearrangements).as defined by both patient and disease characteristics such as age and cytogenetics
5. Compare the incidence of severe infections and severe organ toxicity in the treatment arms and with previous protocols

Conditions and MedDRA coding

Acute Myeloid Leukemia (Pediatric 0-18 years)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. AML as defined by the diagnostic criteria in the protocol
2. Age below 19 years at time of diagnosis
3. Written informed consent

Exclusion criteria 11

1. Previous chemotherapy or radiotherapy. This includes patient with secondary AML after previous cancer therapy. They can be treated according to the protocol but will not be included in the study population. Secondary AML has a poorer response to chemotherapy but may benefit from SCT if the procedure can be tolerated.
2. AML secondary to previous bone marrow failure syndrome.
3. Down syndrome (DS). Patients with myeloid leukaemia of Down syndrome are recommended to be treated according to the international ML-DS protocol. Patients with AML and DS older than 5 years who often lack GATA1 mutation and do not have typical myeloid leukaemia of DS may be treated according to the protocol but will not be included in the study population.
4. Acute promyelocytic leukaemia (APL). These patients are recommended treatment according to the international APL Study.
5. Myelodysplastic syndrome (MDS). These patients are recommended treatment according to EWOG-MDS.
6. Juvenile Myelomonocytic Leukaemia (JMML). These patients are recommended treatment according to EWOG-MDS.
7. Known intolerance to any of the chemotherapeutic drugs in the protocol.
8. Fanconi anemia
9. Major organ failure precluding administration of planned therapy
10. Positive pregnancy test
11. Lactating female or female of childbearing potential not using adequate contraception

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. The fraction of patients who achieve an MRD level below 0.1%, as quantified by flow cytometry, after the first induction course. (aim 1)
2. The fraction of patients who achieve an MRD level below 0.1%, as quantified by flow cytometry, after the second induction course (aim 2)
3. For patients with fusion genes MRD levels after course 1 and 2 (aim 3)

Secondary endpoints 5

1. Event-free survival and overall survival at five years
2. The median MRD after course 1 and course 2.
3. The rate of CR after one and two induction courses.
4. Cardiac function after one and five years.
5. Frequency of severe adverse events as defined in section 14.2.3 in the protocol, early deaths and deaths in CR

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vaestra Goetalandsregionen

Sponsor organisation

Vaestra Goetalandsregionen

Address

Regionens Hus

City

Vänersborg

Postcode

462 80

Country

Sweden

Scientific contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Jonas Abrahamsson

Public contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Jonas Abrahamsson

Third parties 1

Locations

7 EU/EEA countries · 41 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 50 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications