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NCT02399917

Lirilumab and Azacitidine in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia

Terminated Phase 2 Results posted Last updated 24 September 2019
What this trial tests

Phase 2 trial testing Azacitidine in Acute Biphenotypic Leukemia in 36 participants. Terminated before completion.

Timeline
20 April 2015
Primary endpoint
12 July 2018
12 July 2018

Quick facts

Lead sponsorM.D. Anderson Cancer Center
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment36
Start date20 April 2015
Primary completion12 July 2018
Estimated completion12 July 2018
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

M.D. Anderson Cancer Center — full company profile →

Who can join

18 and older, any sex, with Acute Biphenotypic Leukemia or Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome. 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.

Maximum Tolerated Dose of Iirilumab in Combination With 5-azacitidine Primary · Up to 28 days

To identify the dose at which \<2/6 participants experience Dose Limiting Toxicities (DLT). The dose level at which 0-1/6 participants experience a DLT in the first 28 days of treatment will be the maximum tolerated dose (MTD) and would be used to treat an additional 34 participants in the phase II potion of the study. (Part A, Lead-In Phase)

GroupValue95% CI
All Phase 1 Participants3.0
Participants With an Objective Response Primary · Up to 3 months

Objective Response Rate (ORR) will be monitored using the Bayesian approach of Thall, Simon, Estey and the extension by Thall and Sung. Overall response rate (ORR), defined as complete remission (CR) + CR with incomplete platelet recovery (CRp) + CR with incomplete count recovery (CRi) + partial response (PR) + marrow clearance of blasts + hematological improvement within 3 months of treatment initiation among adult patients with refractory/relapsed Acute Myelogenous Leukemia (AML) (Phase II)

GroupValue95% CI
Phase 1b Lead-in Cohort 12
Phase 1b Lead-in Cohort 21
Phase 22
Duration of Response Secondary · Up to 2.5 years

The date of Objective Response to the date of loss of response or last follow-up.

GroupValue95% CI
Phase 27.72.0 – 17.0
Overall Survival Secondary · Up to 2 years

Overall Survival (OS) is defined: Time of presentation to date of death or censored at last follow-up date.

GroupValue95% CI
Phase 23.50.4 – 22.2
Disease Free Survival Secondary · Up to 2.5 years

Disease Free Survival (DFS) is defined: Time from date of treatment start until the date of first objective documentation of disease-relapse

GroupValue95% CI
Phase 27.72.0 – 17.0

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to two and a half years.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase 1b Lead-in Cohort 1
Serious: 6/6 (100%)
Deaths: 4/6
Phase 1b Lead-in Cohort 2
Serious: 6/6 (100%)
Deaths: 2/6
Phase 2
Serious: 20/24 (83%)
Deaths: 9/24

Serious adverse events (29 terms)

ReactionSystemPhase 1b Lead-in Cohort 1Phase 1b Lead-in Cohort 2Phase 2
Lung InfectionInfections and infestations
Neutropenic FeverInfections and infestations
InfectionInfections and infestations
Blood and Lymphatic system disordersBlood and lymphatic system disorders
SepsisInfections and infestations
Abdominal PainGastrointestinal disorders
HypotensionVascular disorders
Respiratory FailureRespiratory, thoracic and mediastinal disorders
Abdominal DistensionGastrointestinal disorders
ConstipationGastrointestinal disorders
DizzinessNervous system disorders
FatigueGeneral disorders
FeverGeneral disorders
Gastrointestinal Disorders OtherGastrointestinal disorders
HematuriaRenal and urinary disorders
HypernatremiaMetabolism and nutrition disorders
HypokalemiaMetabolism and nutrition disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Ileal PerforationGastrointestinal disorders
Joint InfectionInfections and infestations
MucositisGastrointestinal disorders
Multi-Organ FailureGeneral disorders
PainGeneral disorders
Respiratory otherRespiratory, thoracic and mediastinal disorders
Scrotal InfectionInfections and infestations
Other adverse events (44 terms — click to expand)

ReactionSystemPhase 1b Lead-in Cohort 1Phase 1b Lead-in Cohort 2Phase 2
ConstipationGastrointestinal disorders
PainGeneral disorders
DiarrheaGastrointestinal disorders
FeverGeneral disorders
HypotensionVascular disorders
InfectionInfections and infestations
Infusion ReactionGeneral disorders
Pleural EffusionRespiratory, thoracic and mediastinal disorders
Urinary Tract InfectionInfections and infestations
Neutropenic FeverInfections and infestations
Sinus BradycardiaCardiac disorders
FallInjury, poisoning and procedural complications
HyperbilirubinemiaInvestigations
Pericardial EffusionCardiac disorders
Aspartate Aminotransferase IncreasedInvestigations
EdemaGeneral disorders
HematuriaRenal and urinary disorders
InsomniaPsychiatric disorders
PneumoniaInfections and infestations
Respiratory FailureRespiratory, thoracic and mediastinal disorders
Acute Kidney InjuryRenal and urinary disorders
AnorexiaMetabolism and nutrition disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
HeadacheGeneral disorders
HypokalemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
HypophosphatemiaMetabolism and nutrition disorders
NauseaGastrointestinal disorders
SinusitisInfections and infestations
Abdominal DistensionGastrointestinal disorders
Elevated Alanine Aminotransferase increasedInvestigations
Atrial FibrillationCardiac disorders
BruisingSkin and subcutaneous tissue disorders
HyperglycemiaMetabolism and nutrition disorders
HypertensionVascular disorders
MucositisGastrointestinal disorders
MyalgiaMusculoskeletal and connective tissue disorders
PruritisSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
HypocalcemiaMetabolism and nutrition disorders

Most-reported serious reactions: Lung Infection, Neutropenic Fever, Infection, Blood and Lymphatic system disorders, Sepsis, Abdominal Pain, Hypotension, Respiratory Failure.

Data from ClinicalTrials.gov NCT02399917 adverse events section.

Sponsor's own description

This phase II trial studies the side effects lirilumab and azacitidine and to see how well they work in treating patients with acute myeloid leukemia that has not responded to treatment or has returned after a period of improvement. Monoclonal antibodies, such as lirilumab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving lirilumab with azacitidine may be an effective treatment for relapsed or refractory acute myeloid leukemia.

Publications & conference data

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

  1. Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials.
    Cheng Y, He C, Wang M, Ma X, et al · · 2019 · cited 760× · PMID 31871779 · DOI 10.1038/s41392-019-0095-0
  2. Immune checkpoint therapy in liver cancer.
    Xu F, Jin T, Zhu Y, Dai C. · · 2018 · cited 299× · PMID 29843754 · DOI 10.1186/s13046-018-0777-4
  3. The Rise of Allogeneic Natural Killer Cells As a Platform for Cancer Immunotherapy: Recent Innovations and Future Developments.
    Veluchamy JP, Kok N, van der Vliet HJ, Verheul HMW, et al · · 2017 · cited 146× · PMID 28620386 · DOI 10.3389/fimmu.2017.00631
  4. Recent developments in epigenetic cancer therapeutics: clinical advancement and emerging trends.
    Nepali K, Liou JP. · · 2021 · cited 122× · PMID 33840388 · DOI 10.1186/s12929-021-00721-x
  5. NK Cell Dysfunction and Checkpoint Immunotherapy.
    Bi J, Tian Z. · · 2019 · cited 118× · PMID 31552017 · DOI 10.3389/fimmu.2019.01999
  6. Epi-drugs in combination with immunotherapy: a new avenue to improve anticancer efficacy.
    Mazzone R, Zwergel C, Mai A, Valente S. · · 2017 · cited 113× · PMID 28572863 · DOI 10.1186/s13148-017-0358-y
  7. A phase 1 study of lirilumab (antibody against killer immunoglobulin-like receptor antibody KIR2D; IPH2102) in patients with solid tumors and hematologic malignancies.
    Vey N, Karlin L, Sadot-Lebouvier S, Broussais F, et al · · 2018 · cited 104× · PMID 29707140 · DOI 10.18632/oncotarget.24832
  8. Natural killer cell-based immunotherapy for acute myeloid leukemia.
    Xu J, Niu T. · · 2020 · cited 83× · PMID 33287858 · DOI 10.1186/s13045-020-00996-x

Verify or expand the search:

Other trials of Azacitidine

Trials testing the same drug.

Other recruiting trials for Acute Biphenotypic Leukemia

Currently open trials in the same condition.

Other M.D. Anderson Cancer Center trials

Trials by the same sponsor.

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