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NCT01051063

Evaluation of a New Anti-cancer Immunotherapy in Adult Acute Myeloid Leukemia Patients With a Suboptimal Clinical Response to Induction Chemotherapy

Completed Phase 1 Results posted Last updated 29 November 2018
What this trial tests

Phase 1 trial testing GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2130579A in Leukaemia, Myelocytic, Acute in 17 participants. Completed in 26 April 2016.

Timeline
9 December 2009
Primary endpoint
26 April 2016
26 April 2016

Quick facts

Lead sponsorGlaxoSmithKline
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment17
Start date9 December 2009
Primary completion26 April 2016
Estimated completion26 April 2016
Sites22 locations across France, United States, Germany

Drugs / interventions tested

Conditions studied

Sponsor

GlaxoSmithKline — full company profile →

Who can join

18 and older, any sex, with Leukaemia, Myelocytic, Acute. 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 Patients With Severe Toxicities Primary · During the entire study (from Month 0 to Month 49)

Severe toxicities (as classified according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0) during the study treatment period defined as a study product-related or possibly study product-related: * Grade 4 toxicity (exception: study product-related or possibly study product-related Grade 4 fatigue - including lethargy, asthenia, and malaise - had to have a duration of at least 48 hours to be taken into account). * Grade 3 toxicity lasting for at least 48 hours (exceptions: myalgia, arthralgia, headache, and fever, regardless of duration).

GroupValue95% CI
Complete Remission Group1
Partial Remission Group0
Number of Patients With Best Overall Response, Defined by Either Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD) Primary · During the entire study (from Month 0 to Month 49)

CR = having \< 5% blasts in aspirate sample with marrow spicules and with a count of ≥ 200 nucleated cells, no blasts with Auer rods or persistence of extramedullary disease; different phenotype (by flow cytometry) to the pre-treatment specimen; absolute neutrophil count \> 1000/mm3; platelet count ≥ 100 000/mm3 and being independent of red blood cell (RBC) transfusions. PR = a decrease of ≤ 50% in the % of blasts in bone marrow aspirate compared to Visit 4; being independent of RBC transfusions and the absolute neutrophil ≥ 1000/mm3 and platelet counts and ≥ 100 000/mm3. SD = no sufficient

CR
GroupValue95% CI
Complete Remission Group5
Partial Remission Group0
PR
GroupValue95% CI
Complete Remission Group0
Partial Remission Group3
SD
GroupValue95% CI
Complete Remission Group6
Partial Remission Group1
PD
GroupValue95% CI
Complete Remission Group1
Partial Remission Group1
Anti-WT1 Seropositivity Rate Secondary · At baseline (PRE), weeks (W) 5, 9, 13, 15, 21, 32, 40, 54, at months 15, 18, 21, 24, 30, 36, 42 and 49 (concluding visit), as well as follow-up visits 1 to 4

Seropositivity rate was defined as the number of patients with anti-WT1 antibody concentrations greater than or equal to (≥) 9 Enzyme-Linked Immunosorbent Assay (ELISA) units per milliliter (EU/mL).

Anti-WT1 PRE
GroupValue95% CI
Total Treated Group0
Anti-WT1 Post-dose 2, Week 5
GroupValue95% CI
Total Treated Group1
Anti-WT1 Post-dose 4, Week 9
GroupValue95% CI
Total Treated Group10
Anti-WT1 Post-dose 6, Week 13
GroupValue95% CI
Total Treated Group12
Anti-WT1 Post-dose 6, Week 15
GroupValue95% CI
Total Treated Group12
Anti-WT1 Post-dose 8, Week 21
GroupValue95% CI
Total Treated Group9
Anti-WT1 Post-dose 12, Week 32
GroupValue95% CI
Total Treated Group6
Anti-WT1 Post-dose 13, Week 40
GroupValue95% CI
Total Treated Group5
Anti-WT1 Antibody Concentrations Secondary · At baseline (PRE), weeks (W) 5, 9, 13, 15, 21, 32, 40, 54, at months 15, 18, 21, 24, 30, 36, 42 and 49 (concluding visit), as well as follow-up visits 1 to 4

Antibody concentrations were expressed as geometric mean concentrations, measured in ELISA units per milliliter (EU/mL).

Anti-WT1 PRE
GroupValue95% CI
Total Treated Group4.54.5 – 4.5
Anti-WT1 Post-dose 2, Week 5
GroupValue95% CI
Total Treated Group5.43.7 – 7.9
Anti-WT1 Post-dose 4, Week 9
GroupValue95% CI
Total Treated Group52.018.6 – 145.4
Anti-WT1 Post-dose 6, Week 13
GroupValue95% CI
Total Treated Group123.850.0 – 306.5
Anti-WT1 Post-dose 6, Week 15
GroupValue95% CI
Total Treated Group138.365.3 – 292.8
Anti-WT1 Post-dose 8, Week 21
GroupValue95% CI
Total Treated Group105.035.6 – 309.7
Anti-WT1 Post-dose 12, Week 32
GroupValue95% CI
Total Treated Group136.429.4 – 632.2
Anti-WT1 Post-dose 13, Week 40
GroupValue95% CI
Total Treated Group113.021.1 – 603.4
Anti-WT1 Antibody Response Secondary · At baseline (PRE), weeks (W) 5, 9, 13, 15, 21, 32, 40, 54, at months 15, 18, 21, 24, 30, 36, 42 and 49 (concluding visit), as well as follow-up visits 1 to 4

The anti-WT1 antibody response was defined as: For initially seronegative patients, post-vaccination antibody concentration ≥ 9 EU/mL; For initially seropositive patients, post-vaccination antibody concentration ≥ 2 fold the pre-vaccination antibody concentration.

Anti-WT1 Post-dose 2, Week 5
GroupValue95% CI
Total Treated Group1
Anti-WT1 Post-dose 4, Week 9
GroupValue95% CI
Total Treated Group10
Anti-WT1 Post-dose 6, Week 13
GroupValue95% CI
Total Treated Group12
Anti-WT1 Post-dose 6, Week 15
GroupValue95% CI
Total Treated Group12
Anti-WT1 Post-dose 8, Week 21
GroupValue95% CI
Total Treated Group9
Anti-WT1 Post-dose 12, Week 32
GroupValue95% CI
Total Treated Group6
Anti-WT1 Post-dose 13, Week 40
GroupValue95% CI
Total Treated Group5
Anti-WT1 Post-dose 16, Week 54
GroupValue95% CI
Total Treated Group5
Number of Subjects With Any and Related Unsolicited Adverse Events (AEs) Secondary · Starting with the first administration of study treatment and ending 30 days after the last study treatment administration

An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Related = AE assessed by the investigator as causally related to the study treatment.

Any AE(s)
GroupValue95% CI
Total Treated Group15
Related AE(s)
GroupValue95% CI
Total Treated Group10
Number of Subjects With Study Treatment Failure Secondary · During the entire study (from Month 0 to Month 49)

Study treatment failure was defined as withdrawal from investigational product because of disease progression or death. Among the characteristics evaluated were: Progression, Death in absence of Relapse, Relapse or progression or Death (Progression Free Survival event), Death \[An event that was part of the natural course of the disease under study (i.e., disease progression, recurrence) was captured in the study as an efficacy measure; therefore it did not need to be reported as an SAE\], Autopsy performed and Cause of death.

Progression - yes
GroupValue95% CI
Complete Remission Group6
Partial Remission Group5
Progression - no
GroupValue95% CI
Complete Remission Group6
Partial Remission Group0
Death in absence of Relapse - yes
GroupValue95% CI
Complete Remission Group0
Partial Remission Group0
Death in absence of Relapse - no
GroupValue95% CI
Complete Remission Group12
Partial Remission Group5
Progression Free Survival event - yes
GroupValue95% CI
Complete Remission Group6
Partial Remission Group5
Progression Free Survival event - no
GroupValue95% CI
Complete Remission Group6
Partial Remission Group0
Death - yes
GroupValue95% CI
Complete Remission Group4
Partial Remission Group2
Death - no
GroupValue95% CI
Complete Remission Group8
Partial Remission Group3
Number of Subjects With Any or Related Serious Adverse Events (SAEs) Secondary · During the entire study (from Month 0 to Month 49)

SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Related = SAE assessed by the investigator as causally related to the study treatment. An event that was part of the natural course of the disease under study (i.e., disease progression, recurrence) was captured in the study as an efficacy measure, therefore, it did not need to be reported as an SAE. Death due to progressive disease was recorded on a specific form in the CRF, but not as an SAE.

Any SAE(s)
GroupValue95% CI
Total Treated Group7
Related SAE(s)
GroupValue95% CI
Total Treated Group1
Number of Patients With Abnormal Hematological and Biochemical Parameters Secondary · During the entire study (Month 0 to Month 49)

Haematological and biochemical parameters assessed were Alanine aminotransferase, Aspartate aminotransferase, Alkaline Phosphatase, Bilirubin, Creatinine, Gamma-glutamyl transpeptidase, Hemoglobin, Hypercalcemia, Hyperkalemia, Hypernatremia, Hypoalbuminemia, Hypocalcemia, Hypokalemia, Hyponatremia, Leukocytes, Lymphopenia, Neutrophils, Platelets and Proteinuria. Parameters were assessed as per the Common Terminology Criteria for adverse events (CTCAE), where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe but not life-threatening and Grade 4 = life-threatening.

Alanine aminotransferase, Grade 0
GroupValue95% CI
Total Treated Group8
Alanine aminotransferase, Grade 1
GroupValue95% CI
Total Treated Group7
Alanine aminotransferase, Grade 2
GroupValue95% CI
Total Treated Group2
Alanine aminotransferase, Grade 3
GroupValue95% CI
Total Treated Group0
Alanine aminotransferase, Grade 4
GroupValue95% CI
Total Treated Group0
Alanine aminotransferase, Unknown
GroupValue95% CI
Total Treated Group0
Aspartate aminotransferase, Grade 0
GroupValue95% CI
Total Treated Group10
Aspartate aminotransferase, Grade 1
GroupValue95% CI
Total Treated Group6

Adverse events — posted to ClinicalTrials.gov

Time frame: Unsolicited AEs: starting with the first administration of study treatment (Week 1) and ending 30 days after the last study treatment administration (Month 49); SAEs: During the entire study (From Month 0 to Month 49).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Total Treated Group
Serious: 7/17 (41%)
Deaths: 6/17

Serious adverse events (11 terms)

ReactionSystemTotal Treated Group
PneumoniaInfections and infestations
LeukocytosisBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
PyrexiaGeneral disorders
BronchitisInfections and infestations
DiverticulitisInfections and infestations
HypercalcaemiaMetabolism and nutrition disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Hypertensive crisisVascular disorders
Vascular stenosisVascular disorders
Other adverse events (61 terms — click to expand)

ReactionSystemTotal Treated Group
Injection site painGeneral disorders
AnaemiaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
VertigoEar and labyrinth disorders
HeadacheNervous system disorders
ErythemaSkin and subcutaneous tissue disorders
NeutropeniaBlood and lymphatic system disorders
DyspepsiaGastrointestinal disorders
Injection site inflammationGeneral disorders
Injection site reactionGeneral disorders
BronchitisInfections and infestations
FolliculitisInfections and infestations
RhinitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
PruritusSkin and subcutaneous tissue disorders
LeukocytosisBlood and lymphatic system disorders
LymphopeniaBlood and lymphatic system disorders
ArrhythmiaCardiac disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
AstheniaGeneral disorders
IndurationGeneral disorders
Influenza like illnessGeneral disorders
Injection site erythemaGeneral disorders
OedemaGeneral disorders
Oedema peripheralGeneral disorders
PyrexiaGeneral disorders
HypersensitivityImmune system disorders
Bacterial infectionInfections and infestations
NasopharyngitisInfections and infestations
Rib fractureInjury, poisoning and procedural complications
WoundInjury, poisoning and procedural complications
Antinuclear antibody positiveInvestigations
Blood creatine increasedInvestigations
HyperglycaemiaMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
Iron overloadMetabolism and nutrition disorders
MyalgiaMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Pneumonia, Leukocytosis, Neutropenia, Thrombocytopenia, Pyrexia, Bronchitis, Diverticulitis, Hypercalcaemia.

Data from ClinicalTrials.gov NCT01051063 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the clinical activity and safety of a WT1 Antigen-Specific Cancer Immunotherapeutic (WT1 ASCI) as post-induction therapy in adult patients with WT1-positive AML presenting a suboptimal clinical response to induction chemotherapy. The study will also assess whether this treatment induces a specific immune response to the malignancy.

Publications & conference data

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

  1. Therapeutic cancer vaccines: advancements, challenges, and prospects.
    Fan T, Zhang M, Yang J, Zhu Z, et al · · 2023 · cited 314× · PMID 38086815 · DOI 10.1038/s41392-023-01674-3
  2. Trial watch: Peptide vaccines in cancer therapy.
    Vacchelli E, Martins I, Eggermont A, Fridman WH, et al · · 2012 · cited 74× · PMID 23264902 · DOI 10.4161/onci.22428
  3. First-in-human study of WT1 recombinant protein vaccination in elderly patients with AML in remission: a single-center experience.
    Kreutmair S, Pfeifer D, Waterhouse M, Takács F, et al · · 2022 · cited 19× · PMID 35476127 · DOI 10.1007/s00262-022-03202-8
  4. A perspective of immunotherapy for acute myeloid leukemia: Current advances and challenges.
    Chen Y, Wang J, Zhang F, Liu P. · · 2023 · cited 13× · PMID 37153761 · DOI 10.3389/fphar.2023.1151032

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