Venetoclax added to drug combination improves survival in children with relapsed acute myeloid leukemia

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What is this study about?

The study focuses on children who have experienced a return of acute myeloid leukemia, a type of blood cancer. The treatment being tested adds the oral medication venetoclax to a standard chemotherapy combination that includes the medicines fludarabine (given under the skin), cytarabine (given through a vein), and gemtuzumab ozogamicin (also given through a vein). The purpose of the study is to determine whether the addition of venetoclax can improve overall survival, which means the length of time a child lives after starting treatment.

Participants are randomly assigned to receive either the standard chemotherapy regimen alone or the same regimen plus venetoclax. Treatment cycles are given over several weeks, followed by regular clinic visits to monitor health and any side effects. After the treatment period, children continue to be followed for a longer time to see how long they remain alive and to gather information on their recovery.

1 start oral venetoclax

on the first day of the trial you begin taking venetoclax as an oral suspension.

the prescribed dose is 600 mg taken by mouth. the exact schedule (for example, once daily) is defined in the study protocol and must be followed exactly.

2 receive fludarabine infusion

you receive an intravenous infusion of fludarabine.

the dose is 30 mg per square meter of body‑surface area, administered through a vein.

the infusion is given on the days specified by the trial schedule.

3 receive cytarabine infusion

you receive an intravenous infusion of cytarabine.

the dose is 2 g per square meter of body‑surface area, delivered through a vein.

the infusion is given on the same days as the fludarabine infusion, according to the trial schedule.

4 receive gemtuzumab ozogamicin infusion

you receive an intravenous infusion of gemtuzumab ozogamicin.

the dose is 3 mg per square meter of body‑surface area, administered through a vein.

this infusion is given on the days defined by the trial protocol, typically after the fludarabine and cytarabine infusions.

5 continue oral venetoclax throughout treatment cycles

after the initial infusion days, you continue taking venetoclax at the same 600 mg oral dose for the remainder of each treatment cycle.

the number of cycles and total duration are specified in the study protocol and are followed until the end of the trial treatment period.

6 optional azacitidine administration

if the protocol includes azacitidine, it is given by subcutaneous injection.

the dose is 75 mg per square meter of body‑surface area.

the timing and frequency are defined by the trial schedule and must be followed exactly.

Who Can Join the Study?

Be a child, teenager, or young adult who has acute myeloid leukemia (AML) and does not have a genetic change called a FLT3/ITD mutation. This mutation is a specific change in the leukemia cells that can affect treatment.
Have AML that is either a second relapse that has not yet been treated and you are healthy enough for another round of strong chemotherapy, or a first relapse that has not yet been treated and your doctor thinks you cannot handle more chemotherapy that contains a drug called anthracycline.
Not be taking medicines that treat or prevent graft‑versus‑host disease (a problem that can happen after a bone‑marrow transplant) or organ‑rejection medicines for at least 14 days.
Be at least 42 days after any type of cellular therapy (such as a stem‑cell or immune‑cell treatment).
Have good organ function:
- Kidney: a test called eGFR (or a similar measure) must be 60 ml/min/1.73 m² or higher.
- Liver: bilirubin (a waste product) must be no more than 1.5 times the normal upper limit, alkaline phosphatase no more than 2.5 times normal, and ALT (a liver enzyme) no more than 2.5 times normal. Slightly higher ALT is allowed if it is caused by leukemia in the liver or fatty liver disease.
- Heart: no history of heart failure that needs medication, normal left‑ventricular function on an ultrasound (no very low fraction‑shortening or ejection‑fraction), and no signs of heart failure now.
Give written permission by signing an informed consent form (and assent form if you are old enough), together with a parent or legal guardian, before any study procedures begin.
Have a good overall health rating, called a performance status, of 0, 1, or 2 on the ECOG scale (or a Lansky/Karnofsky score of 50% or higher). This means you are able to carry out most daily activities.
Have fully recovered from any short‑term side effects of previous cancer treatments and wait the required time after those treatments (the exact time is detailed in the study protocol).
Not have received strong chemotherapy (called cytotoxic chemotherapy) within the last 14 days, except for steroids, low‑dose cytarabine, or hydroxyurea, which can be given up to 24 hours before starting the study treatment.
Wait at least 21 days after the last dose of any antibody‑drug conjugate (a type of targeted medicine) before starting the study treatment.
Wait at least 21 days after finishing any interleukins, interferons, or other cytokine medicines before starting the study treatment.
Wait at least 14 days after the last dose of a long‑acting blood‑cell growth factor, or at least 7 days after a short‑acting growth factor, before starting the study treatment.
If you have had radiation therapy, wait between 14 and 84 days (depending on how large the radiation area was) before starting the study treatment.
If you have had a bone‑marrow or stem‑cell transplant, wait at least 84 days and have no active graft‑versus‑host disease before joining the study.

Who Cannot Join the Study?

Patients who, in the doctor’s opinion, might not be able to follow the study rules and visits.
Patients who have Down syndrome.
Patients who have Acute promyelocytic leukemia (APL) or Juvenile myelomonocytic leukemia (JMML) – two specific types of blood cancer.
Patients who have disease in the brain‑spinal fluid classified as CNS3 (either isolated or causing symptoms).
Patients who cannot absorb medicines through the stomach or intestines, making it impossible to take the study drug by mouth.
Patients who are already taking another experimental (investigational) medicine that is not part of this study.
Patients with inherited bone‑marrow problems such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or any similar congenital (present from birth) bone‑marrow failure condition.
Patients who are known to be allergic to any of the medicines used in the study.
Patients who have a current, active infection that is not under control.
Patients who are infected with hepatitis C virus (HCV), hepatitis B virus (HBV) (positive surface antigen test), or human immunodeficiency virus (HIV).
Patients who have taken strong or moderate CYP3A enzyme‑inducing drugs (such as rifampin, carbamazepine, phenytoin, or St. John’s wort) within the 7 days before starting the study drug, or who have eaten grapefruit, Seville oranges, or starfruit within 3 days before starting the study drug, or who are allergic to the study drug or its inactive ingredients.
Patients who are pregnant, are breastfeeding, or are of child‑bearing potential and are not using a highly effective birth‑control method, as well as male patients who are not using condoms and agree not to father a child or donate sperm during and after treatment as required.
Patients who have a history of severe liver blood‑vessel damage called veno‑occlusive disease (VOD/SOS) grade 3 or 4, or whose leukemia cells do not have the protein CD33 (they are “CD33 negative”), making the study drug gemtuzumab ozogamicin unsafe for them.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Centre Hospitalier Universitaire De Lille	Lille	France
Oslo Universitetssykehus HF	Oslo	Norway
Hospital Universitario Y Politecnico La Fe	Valencia	Spain

Other Sites

Site Name	City	Country
Hopital Des Enfants	Toulouse	France
Children’s Health Ireland	Dublin	Ireland
Charite Universitaetsmedizin Berlin KöR	Berlin	Germany
Karolinska University Hospital	Solna	Sweden
Robert Debre University Hospital	Paris	France
Instituto Portugues De Oncologia De Lisboa Francisco Gentil E.P.E.	Lisbon	Portugal
Prinses Maxima Centrum voor Kinderoncologie B.V.	Utrecht	The Netherlands
Assistance Publique Hopitaux De Paris	Paris	France
Centre Hospitalier Universitaire De Nantes	Nantes	France
Rigshospitalet	Copenhagen	Denmark
IRCCS Istituto Giannina Gaslini	Genoa	Italy
Universitair Ziekenhuis Gent	Gent	Belgium
Hospital Sant Joan De Deu Barcelona	Esplugues De Llobregat	Spain
St. Anna Kinderspital GmbH	Vienna	Austria
Centre Hospitalier Lyon Sud	Pierre Benite	France
Fondazione IRCCS San Gerardo Dei Tintori	Monza	Italy
Ospedale Pediatrico Bambino Gesu’	Rome	Italy
Universitätsklinikum Essen	Essen	Germany
Hqpzcipk Vele dervzlys	Barcelona	Spain
Fprsdocc npovgiqro Mexcb a Hrgpppp	Prague	Czechia
Hsqgimns Uvemmgzqke Chzxpcc Hudycjxm	Helsinki	Finland
Afickmd Olsmueimqty Usgmslyrnwwwp Cyvkhiaxyorm Dgidk Stgouq E Ddksr Sssryeh Dq Tooyrn	Turin	Italy
Uafipejwdtmnomjitgfcb Mjsyeenw Aus	Munster	Germany
Galned Uchnskzszu Funthgvxp	Frankfurt	Germany
Urulzoquyjrtgsttzgbvh Agqktdbw	Augsburg	Germany

Trial status

Country	Status	Recruitment Start
Austria	Recruiting	01.06.2022
Belgium	Recruiting	01.06.2022
Czechia	Recruiting	01.06.2022
Denmark	Recruiting	01.06.2022
Finland	Recruiting	01.06.2022
France	Recruiting	01.06.2022
Germany	Recruiting	01.06.2022
Ireland	Not recruiting	01.06.2022
Italy	Recruiting	01.06.2022
Norway	Recruiting	01.06.2022
Portugal	Recruiting	01.06.2022
Spain	Recruiting	01.06.2022
Sweden	Recruiting	01.06.2022
The Netherlands	Recruiting	01.06.2022

Trial locations

Investigated drugs:

Venetoclax is an oral medicine that blocks a protein helping cancer cells stay alive. In this study it is added to the usual chemotherapy to see if it can help children with relapsed acute myeloid leukemia live longer.

Fludarabine is a chemotherapy drug given by injection under the skin. It works by interfering with the DNA of cancer cells, which helps stop the cells from growing. It is part of the standard treatment used for all children in the trial.

Cytarabine is a chemotherapy drug given through a vein in a high dose. It stops cancer cells from making DNA, leading to their death. It is another key part of the standard chemotherapy regimen given to every participant.

Gemtuzumab ozogamicin is a targeted therapy given by IV infusion. It attaches to a marker on leukemia cells and delivers a toxin that destroys those cells. In the trial it is combined with the chemotherapy drugs, and the study tests whether adding venetoclax improves the results.

Acute Myeloid Leukemia – Acute Myeloid Leukemia (AML) is a type of blood cancer that starts in the bone marrow. It causes the marrow to produce large numbers of immature white blood cells called myeloblasts. These abnormal cells crowd out normal blood cells, leading to reduced red cells, white cells, and platelets. As the disease progresses, the excess cells can spill into the bloodstream and spread to other organs such as the spleen or liver.

Trial ID:

2023-510160-12-00

Protocol code:

ITCC-101/APAL2020D

NCT ID:

NCT05183035

Trial Phase:

Therapeutic confirmatory (Phase III)

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Venetoclax added to drug combination improves survival in children with relapsed acute myeloid leukemia

What is this study about?

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Who Cannot Join the Study?