A Randomized, Multi-Center Phase III Trial comparing two conditioning regimens (CloFluBu and BuCyMel) in children with Acute Myeloid Leukemia undergoing allogeneic stem cell transplantation.

Phase 3

Conditions: Acute Myeloid Leukemia (AML)
blood cancer
10024324

Registration Number: NL-OMON53923

Lead Sponsor: Västra Götaland Regionen

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 30

Inclusion Criteria

Inclusion criteria for randomization part of the study:
• Age <=18 years at time of initial AML, age <= 21 years at transplantation.
• HCT is performed in a study participating center
• All women of childbearing potential who have to have a negative pregnancy
test within 2 weeks prior to the start of treatment.
• Signed informed consent.
• Any relapsed AML after initial treatment according to a defined international
AML protocol. (NOPHO-DBH AML 2012/new protocol), or AML in first remission with
transplant indications and treatment according to national AML protocol
(NOPHO-DBH AML 2012 or new protocol).
• In hematological remission, defined as
o < 5 % leukemic blasts confirmed by flow cytometry (in patients with an
informative leukemia associated immunophenotype) in a bone marrow sample taken
<=14 days prior to start of conditioning and
o no evidence of extramedullary disease, including in CNS and
o no leukemic blasts in the peripheral blood (verified by flow cytometry in
case immature cells are detected in the peripheral blood differential).
• Patients must have a related or unrelated donor fulfilling any of the
following criteria
o HLA 10/10 allelic matched, identical, sibling BM donor or
o HLA 10/10 or 9/10 allelic matched related/unrelated BM or PBSC donor or
o HLA 5-6/6 unrelated or 6-7-8/8 unrelated Cord Blood (UCB).

Inclusion criteria for observation/registration only:
• Diagnosis of acute myeloid leukemia
• Indication for allogeneic stem cell transplantation, as defined by primary
treatment protocol or treating physician.
• Age <=18 years at time of initial AML, age <= 21 years at transplantation.
• Not eligible for randomization, either due to lack of consent or not
fulfilling inclusion criteria for interventional part of the study.
• Signed informed consent to prospectively register follow-up data.

Exclusion Criteria

Exclusion criteria for randomization part of the study:
• Diagnosis of juvenile myelomonocytic leukemia (JMML).
• History of previous malignancy (AML diagnosed as secondary cancer).
• Known diagnosis of Fanconi anemia.
• Prior autologous or allogeneic hematopoietic stem cell transplant.
• Planned prophylactic DLI or other immunotherapeutic interventions after HCT
that are not included in the upfront protocol,
• Planned anti-leukemic medication after HCT that are not included in the
upfront protocol
• Known intolerance to any of the chemotherapeutic drugs in the protocol.
• Major organ failure precluding administration of planned chemotherapy.
• Patients with uncontrolled bacterial, viral, or fungal infections (currently
taking medication and with progression or no clinical improvement) at time of
enrollment.
• Severe concomitant disease that does not allow treatment according to the
protocol at the investigator*s discretion, e.g. malformation syndromes, cardiac
malformations, metabolic disorders, renal impairment (<30% of normal glomerular
filtration rate), severe pulmonary, hepatic or cardiac impairment due to
toxicity or infection.
• Karnofsky / Lansky score < 50%
• Females who are pregnant (positive serum or urine βHCG) or breastfeeding.
• Females of childbearing potential or men who have sexual contact with females
of childbearing potential unwilling to use effective forms of birth control or
abstinence for one year after transplantation.
• Subjects unwilling or unable to comply with the study procedures.

Exclusion criteria for observation/registration only:
• Diagnosis of Myelodysplastic syndrome (MDS).
• Diagnosis of Juvenile myelomonocytic leukemia (JMML).
• Age above 21 years at time of transplantation
• No consent is given to prospectively register outcome data
• Prior autologous or allogeneic hematopoietic stem cell transplant.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary end-point is a comparison of the 2-year acute grade III to IV-free,<br /><br>chronic nonlimited GVHD-free, relapse-free survival (GRFS) between the 2 arms<br /><br>of the trial. GRFS is defined as the time from randomization to the first event<br /><br>(acute GvHD III-IV, chronic nonlimited GvHD, relapse, death) or last follow-up.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Exploratory endpoints in both interventional and observational parts of the<br /><br>study:<br /><br>- Disease free Survival (DFS)<br /><br>- Overall Survival (OS)<br /><br>- Cumulative incidence of relapse (CIR)<br /><br>- Transplant-related Mortality (TRM)<br /><br>- Hematologic Recovery<br /><br>- Graft Failure (GF)<br /><br>- Immunereconstitution<br /><br>- Acute GVHD<br /><br>- Chronic GVHD<br /><br>- Infections<br /><br>- Toxicity</p><br>