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NCT01861002

A Phase I Study of 5-Azacytidine in Combination With Chemotherapy for Children With Relapsed or Refractory ALL or AML

Completed Phase 1 Results posted Last updated 9 June 2021
What this trial tests

Phase 1 trial testing Azacytidine in Lymphoblastic Leukemia, Acute, Childhood in 15 participants. Completed in 28 July 2014.

Timeline
22 May 2013
Primary endpoint
28 July 2014
28 July 2014

Quick facts

Lead sponsorTherapeutic Advances in Childhood Leukemia Consortium
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment15
Start date22 May 2013
Primary completion28 July 2014
Estimated completion28 July 2014
Sites23 locations across Canada, United States, Australia

Drugs / interventions tested

Conditions studied

Sponsor

Therapeutic Advances in Childhood Leukemia Consortium

Who can join

Adults 1 to 21, any sex, with Lymphoblastic Leukemia, Acute, Childhood or Myelogenous Leukemia, Acute, Childhood. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) Primary · From Day 1 to Day 42 (Cycle 1)

To evaluate the side effects of giving Azacytidine before and during chemotherapy using the standard drugs Fludarabine, Cytarabine, IT Cytarabine (AML patients) and IT methotrexate (ALL patients)

# of patients with DLT
GroupValue95% CI
Dose 75 mg/m2/Day Azacytidine Diagnosed With AML0
Dose 75 mg/m2/Day Azacytidine Diagnosed With ALL0
# of patients without DLT
GroupValue95% CI
Dose 75 mg/m2/Day Azacytidine Diagnosed With AML12
Dose 75 mg/m2/Day Azacytidine Diagnosed With ALL2
# of patients not evaluable
GroupValue95% CI
Dose 75 mg/m2/Day Azacytidine Diagnosed With AML1
Dose 75 mg/m2/Day Azacytidine Diagnosed With ALL0
Disease Response Rate After Treatment Secondary · Between Days 36-42 of Courses 1 and 2

CR is defined as a bone marrow with \< 5% blast by morphology, no evidence of extramedullary disease, and recovery of peripheral counts (ANC ≥ 1000/μl and platelet counts ≥ 100,000/μl). CR with incomplete count recovery (CRi) was defined as CR without recovery of ANC and/or platelets. Partial response (PR) was defined as complete disappearance of circulating blasts and a decrease of at least 50% of blasts in the bone marrow. Progressive disease (PD) was defined as an increase of at least 25% in the absolute number of bone marrow or circulating blasts, development of new sites of extramedullary

GroupValue95% CI
Dose 75 mg/m2/Day for AML Patients6
Dose 75 mg/m2/Dose Azacytidine for ALL Patients0
Dose 75 mg/m2/Day for AML Patients1
Dose 75 mg/m2/Dose Azacytidine for ALL Patients0
Dose 75 mg/m2/Day for AML Patients1
Dose 75 mg/m2/Dose Azacytidine for ALL Patients1
Dose 75 mg/m2/Day for AML Patients1
Dose 75 mg/m2/Dose Azacytidine for ALL Patients1

Adverse events — posted to ClinicalTrials.gov

Time frame: From date of first dose of AZA until 30 days following the last dose of protocol therapy (approximately from Day 0 to Day 112). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

AML Cohort: 75 mg/m2/Day
Serious: 5/13 (38%)
Deaths: 0/13
ALL Cohort: 75 mg/m2/Day
Serious: 1/2 (50%)
Deaths: 0/2

Serious adverse events (6 terms)

ReactionSystemAML Cohort: 75 mg/m2/DayALL Cohort: 75 mg/m2/Day
Febrile neutropeniaBlood and lymphatic system disorders
Infections and infestations - Other, specifyInfections and infestations
FeverGeneral disorders
HypokalemiaMetabolism and nutrition disorders
HypotensionVascular disorders
SepsisInfections and infestations
Other adverse events (102 terms — click to expand)

ReactionSystemAML Cohort: 75 mg/m2/DayALL Cohort: 75 mg/m2/Day
HypokalemiaMetabolism and nutrition disorders
NauseaGastrointestinal disorders
Platelet count decreasedBlood and lymphatic system disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Neutrophil count decreasedBlood and lymphatic system disorders
White blood cell decreasedInvestigations
AnemiaBlood and lymphatic system disorders
FeverGeneral disorders
HypoalbuminemiaMetabolism and nutrition disorders
Febrile neutropeniaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
ConstipationGastrointestinal disorders
HypercalcemiaMetabolism and nutrition disorders
Abdominal painGastrointestinal disorders
HyperglycemiaMetabolism and nutrition disorders
HypomagnesemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
PainGeneral disorders
Skin & subcutaneous tissue disorder-OtherSkin and subcutaneous tissue disorders
AnorexiaMetabolism and nutrition disorders
BruisingInjury, poisoning and procedural complications
DiarrheaGastrointestinal disorders
HypophosphatemiaMetabolism and nutrition disorders
Blood bilirubin increasedInvestigations
HeadacheNervous system disorders
Infections and infestations - Other, specifyInfections and infestations
Lymphocyte count decreasedBlood and lymphatic system disorders
Mucositis oralGastrointestinal disorders
PruritusSkin and subcutaneous tissue disorders
Allergic reactionImmune system disorders
DizzinessNervous system disorders
GGT increasedInvestigations
HypermagnesemiaMetabolism and nutrition disorders
HypertriglyceridemiaMetabolism and nutrition disorders
Nervous system disorders - Other, specifyNervous system disorders
Non-cardiac chest painGeneral disorders
Sinus bradycardiaCardiac disorders
Sinus tachycardiaCardiac disorders
Activated partial thromboplastin time prolongedInvestigations

Most-reported serious reactions: Febrile neutropenia, Infections and infestations - Other, specify, Fever, Hypokalemia, Hypotension, Sepsis.

Data from ClinicalTrials.gov NCT01861002 adverse events section.

Sponsor's own description

This is a Phase I study with a conditional cohort expansion phase to evaluate the feasibility of, and to obtain preliminary efficacy data about, pretreatment with Azacytidine (AZA) for 5 days followed by fludarabine/cytarabine chemotherapy regimen in pediatric acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients who are refractory to primary treatment or who relapsed.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Collaborative Efforts Driving Progress in Pediatric Acute Myeloid Leukemia.
    Zwaan CM, Kolb EA, Reinhardt D, Abrahamsson J, et al · · 2015 · cited 276× · PMID 26304895 · DOI 10.1200/jco.2015.62.8289
  2. Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies.
    Zhao A, Zhou H, Yang J, Li M, et al · · 2023 · cited 81× · PMID 36797244 · DOI 10.1038/s41392-023-01342-6
  3. A phase 1 study of azacitidine combined with chemotherapy in childhood leukemia: a report from the TACL consortium.
    Sun W, Triche T, Malvar J, Gaynon P, et al · · 2018 · cited 44× · PMID 29339403 · DOI 10.1182/blood-2017-09-803809
  4. Novel agents for the treatment of childhood acute leukemia.
    Annesley CE, Brown P. · · 2015 · cited 41× · PMID 25830014 · DOI 10.1177/2040620714565963
  5. Overcoming Glucocorticoid Resistance in Acute Lymphoblastic Leukemia: Repurposed Drugs Can Improve the Protocol.
    Olivas-Aguirre M, Torres-López L, Pottosin I, Dobrovinskaya O. · · 2021 · cited 34× · PMID 33777761 · DOI 10.3389/fonc.2021.617937
  6. Molecular therapeutic approaches for pediatric acute myeloid leukemia.
    Tasian SK, Pollard JA, Aplenc R. · · 2014 · cited 29× · PMID 24672775 · DOI 10.3389/fonc.2014.00055
  7. An Overview of Advances in Rare Cancer Diagnosis and Treatment.
    Christyani G, Carswell M, Qin S, Kim W. · · 2024 · cited 17× · PMID 38256274 · DOI 10.3390/ijms25021201
  8. Treatment of Acute Myeloid Leukemia in Adolescent and Young Adult Patients.
    Seval GC, Ozcan M. · · 2015 · cited 16× · PMID 26239248 · DOI 10.3390/jcm4030441

Verify or expand the search:

Other trials of Azacytidine

Trials testing the same drug.

Other recruiting trials for Lymphoblastic Leukemia, Acute, Childhood

Currently open trials in the same condition.

Other Therapeutic Advances in Childhood Leukemia Consortium trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01861002.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing