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. 2023 Apr 29;16:297–308. doi: 10.2147/OTT.S263829

Table 1.

Clinical Trials Investigating the Clinical Efficacy of Gemtuzumab Ozogamicin in Newly Diagnosed Pediatric Acute Myeloid Leukemia

Study Name Recruitment Period Patients (n) Age Range GO Dose Regimen Clinical Efficacy Toxicity
NRCI MRC AML158 July 2002 – June 2006 1113, 58 patients aged 0–14 years 0–71 years Patients were randomized to receive:
Induction 1 (n=1113):

  • a single dose of GO (3 mg/m2), in combination with 1) DA, or 2) ADE, or 3) FLAG-Ida (n=8, patients aged 0–14 years), or

  • no-GO (n=6, patients aged 0–14 years)


Consolidation 1 (n=948):

  • a single dose of GO (3 mg/m2) in combination with 1) MACE, or 2) Ara-C (n=29, patients aged 0–14 years), or

  • no-GO (n=29, patients aged 0–14 years)
  • Total cohort: GO vs no-GO:
    • 5-year OS: 43% vs 41%, p=0.3
    • RFS: 39% vs 35% p=0.09
    • 5-year CIR: 46% vs 50%, p=0.12
  • Total cohort: GO vs no-GO in patients with favorable cytogenetics (n=194):
    • 5-year OS: 79% vs 51%, p<0.001
  • Total cohort: GO vs no-GO in intermediate risk patients:
    • OS: OR: 0.86 (95% CI 0.70–1.07)
  • Patients aged 0–14 years:
    • OS: OR: 0.09 (95% CI 0.01–1.43)

  • GO was well tolerated. No significant increase in toxicity vs the no-GO group.

  • No increased liver toxicity.

  • No results separately for pediatric population.
NRCI MRC AML179 June 2009 – October 2011 788, 29 patients aged 0–16 years 0–60 years Patients were randomized to receive:
Induction 1 (n=788):

  • a single dose of GO (3 mg/m2) in combination with ADE (n=14, patients aged 0–16 years), or

  • a single dose of GO (6 mg/m2) in combination with ADE (n=15, patients aged 0–16 years)
  • Total cohort: 6 mg/m2 vs 3 mg/m2 GO dose:
    • 4-year OS: 47% vs 50%, p=0.3
    • 4-year RFS: 38% vs 44%, p=0.3
  • Patients 0–16 years:
    • OS: OR: 0.56 (95% CI 0.14–2.23)
  • Total cohort: 6 mg/m2 vs 3 mg/m2 GO dose:
    • VOD: 5.6% vs 0.5%, p<0.001
    • 30-day mortality: 7% vs 3%, p=0.02
    • 60-day mortality: 9% vs 5%, p=0.01
    • alanine transaminase (ALT): 17% vs 7%, p=0.01
    • creatinine: 1% vs 2%, p=0.02
    • hematuria: 1% vs 2%, p=0.02

  • No results separately for pediatric population.
St. Jude AML 026,7 2002–2008 216 2 days – 21.4 years Patients were non-randomly assigned to receive:
Induction 2:

  • ADE with or without GO (3 mg/m2), for patients with >25% bone marrow blasts after induction 1 (GO: n=9)


Induction 3:

  • GO monotherapy (6 mg/m2) for patients with MRD >0.1% after induction 2 (GO: n=17)


Amendment:
Induction 2:

  • ADE with GO (3 mg/m2), for patients with MRD >1% after induction 1 (GO: n=20)
  • GO vs no-GO:
    • 5-year OS: 55.0% vs 36.4%, p=0.28
    • 5-year EFS: 50.0% vs 31.8%, p=0.28

  • In the GO group: 27 of the 29 patients had decreased MRD levels after treatment

  • Toxicity was not separately reported for the GO group.
COG
AAML03P110,12,13 		December 2003 – November 2005 350 25 days - 21.6 years All patients non-randomly received (n=350):
Induction 1 (day 6):

  • a single dose of GO (3 mg/m2) in combination with ADE10


Consolidation 2 (day 7):

  • a single dose of GO (3 mg/m2) in combination with MA (for patients not undergoing HSCT)

  • CR: 83% after 1 course, 87% after course 2

  • 3-year OS: 66%

  • 3-year EFS: 53%

  • The toxicities were comparable to a normal AML chemotherapy regimen, with infections being most frequently reported.

  • VOD rate did not differ significantly from those seen with other regimens.
COG
AAML053111−13,18 		August 2006 – June 2010 1022 30 days – 29 years Patients were randomized to receive:
Induction 1 (day 6):

  • a single dose of GO (3 mg/m2) in combination with ADE10 (n=511), and:


Consolidation 2 (day 7):

  • a single dose of GO (3 mg/m2) in combination with MA (n=511) (for patients not undergoing HSCT)


Or standard five course chemotherapy alone (n=511)
  • Total cohort: GO vs no-GO:
    • 3-year OS: 69.4% vs 65.4%, p=0.39
    • 3-year EFS: 51.3% vs 46.9%, p=0.04
    • RR: 32.8% vs 41.3%, p=0.01
    • 3-year DFS: 60.6% vs 54.7%, p=0.07
  • In FLT3-ITD patients (AAML03P1 and AAML0531): GO vs no-GO:
    • 3-year OS: 50% vs 49%, p=0.74
    • RR: 37% vs 59%, p=0.02
    • DFS: 47% vs 41%, p=0.5
    • TRM: 16% vs 0%, p=0.01
  • In KMT2A-rearranged patients: GO vs no-GO:
    • 3-year OS: 63% vs 53%, p=0.05
    • 3-year EFS: 48% vs 29%, p<0.001
    • RR: 40% vs 66%, p<0.001
    • DFS: 57% vs 33%, p<0.01
  • In infant patients (age <1 year): GO vs no-GO:
    • 5-year OS: 66% vs 57%, p=0.22
    • 5-year EFS: 47% vs 37%, p=0.19
    • RR: 37% vs 55%, p=0.06
    • DFS: 57% vs 42%, p=0.09
  • GO vs no-GO:
    • 5-year TRM: 8.6% vs 5.9%, p=0.09 (especially in the low-risk group (8 vs 2 patients, p=0.02)).
    • VOD rate was similar in both groups.
NOPHO-AML 200427 January 2004–2010 120 0–18 years Patients were randomized to receive:
Post-consolidation:

  • No-GO (n=61), or

  • GO (5 mg/m2) 4 weeks after the last consolidation course, and repeated after 3 weeks (n=59)
  • GO vs no-GO:
    • 5-year OS: 74% vs 80% (non-significant)
    • 5-year EFS: 55% vs 51% (non-significant)
    • Relapse: 24 vs 25 patients

  • GO postponed time to relapse with a median of 5 months (non-significant)

  • Overall, the toxicity profile for GO as monotherapy was acceptable.

  • No patients showed signs of VOD.

Abbreviations: ADE, Ara-C + daunorubicin + etoposide; AML, acute myeloid leukemia; CIR, cumulative incidence of relapse; COG, Children’s Oncology Group; CR, complete remission; DA, daunorubicin + cytarabine; EFS, event-free survival; GO, gemtuzumab ozogamicin; HSCT, hematological stem cell transplantation; FLAG-Ida, fludarabine, cytarabine, and idarubicin; MA, mitoxantrone + cytarabine; MACE, amsacrine, cytarabine and etoposide; MRC, Medical Research Council; NOPHO, Nordic Society of Paediatric Haematology and Oncology; NRCI, National Cancer Research Institute; OS, overall survival; RFS, relapse-free survival; RR, relapse rate; VOD, veno-occlusive disease.