NCT00725283

Evaluation of a New Anti-cancer Immunotherapy After Chemotherapy in Adult Patients With Acute Myeloid Leukemia (AML)

Completed Phase 1 Results posted Last updated 7 August 2018

What this trial tests

Phase 1 trial testing GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) in Leukaemia, Myelocytic, Acute in 34 participants. Completed in 22 June 2016.

Timeline

1 October 2008

Primary endpoint
22 June 2016

22 June 2016

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	34
Start date	1 October 2008
Primary completion	22 June 2016
Estimated completion	22 June 2016
Sites	10 locations across France, United States

Drugs / interventions tested

• GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) — full drug profile →

Conditions studied

• Leukaemia, Myelocytic, Acute — all drugs for Leukaemia, Myelocytic, Acute →

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 study treatment period (From Day 0 to Month 48)

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: 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). * An allergic reaction/hypersensitivity Grade 2 toxicit

Encephalitis

Group	Value	95% CI
GSK2130579A Group	1

Rash erythematous

Group	Value	95% CI
GSK2130579A Group	1

Hypersensitivity

Group	Value	95% CI
GSK2130579A Group	1

Angina pectoris

Group	Value	95% CI
GSK2130579A Group	1

Rash

Group	Value	95% CI
GSK2130579A Group	1

Thrombocytopenia

Group	Value	95% CI
GSK2130579A Group	1

Seropositivity Rates for Anti-Wilms Tumor Antigen 1 (WT1) Antibodies Primary · At Baseline [Week 0], at Cycle 1 visits [Weeks 5, 9, 13], at Cycle 2 visits [Weeks 15, 21, 32], at Cycle 3 visits [Weeks 40, 54], at Cycle 4 visits [Months 15, 18, 21, 24, 30 and 49 (concluding visit)] and at Follow-up Visits [Months 52, 55, 58, 61]

Seropostivity rate was defined as the number of patients with anti-WT1 antibody concentration greater than or equal to (≥) the cut-off value of 9 Enzyme-linked Immunosorbent Assay (ELISA) units per milliliter (EU/mL).

Week 0

Group	Value	95% CI
GSK2130579A Group	2

Week 5

Group	Value	95% CI
GSK2130579A Group	6

Week 9

Group	Value	95% CI
GSK2130579A Group	21

Week 13

Group	Value	95% CI
GSK2130579A Group	24

Week 15

Group	Value	95% CI
GSK2130579A Group	21

Week 21

Group	Value	95% CI
GSK2130579A Group	21

Week 32

Group	Value	95% CI
GSK2130579A Group	19

Week 40

Group	Value	95% CI
GSK2130579A Group	18

Concentrations for Anti-WT1 Antibodies Primary · At Baseline [Week 0], at Cycle 1 visits [Weeks 5, 9, 13], at Cycle 2 visits [Weeks 15, 21, 32], at Cycle 3 visits [Weeks 40, 54], at Cycle 4 visits [Months 15, 18, 21, 24, 30 and 49 (concluding visit)] and at Follow-up Visits [Months 52, 55, 58, 61]

Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed as ELISA units per milliliter (EU/mL).

Week 0

Group	Value	95% CI
GSK2130579A Group	4.8	4.4 – 5.2

Week 5

Group	Value	95% CI
GSK2130579A Group	6.3	4.8 – 8.3

Week 9

Group	Value	95% CI
GSK2130579A Group	145.3	66.3 – 318.5

Week 13

Group	Value	95% CI
GSK2130579A Group	337.6	185.2 – 615.4

Week 15

Group	Value	95% CI
GSK2130579A Group	313.4	165.0 – 595.4

Week 21

Group	Value	95% CI
GSK2130579A Group	296.9	162.2 – 543.5

Week 32

Group	Value	95% CI
GSK2130579A Group	285.3	165.3 – 492.4

Week 40

Group	Value	95% CI
GSK2130579A Group	173.7	100.7 – 299.8

Number of Patients With Anti-WT1 Antibody Response Primary · At Cycle 1 visits [Weeks 5, 9, 13], at Cycle 2 visits [Weeks 15, 21, 32], at Cycle 3 visits [Weeks 40, 54], at Cycle 4 visits [Months 15, 18, 21, 24, 30 and 49 (concluding visit)] and at Follow-up Visits [Months 52, 55, 58, 61]

Treatment response was defined as: For initially seronegative patients: post-administration antibody concentration ≥ 9 EU/ML; For initially seropositive patients: post-administration antibody concentration ≥ 2 fold the pre-vaccination antibody concentration.

Week 5

Group	Value	95% CI
GSK2130579A Group	4

Week 9

Group	Value	95% CI
GSK2130579A Group	20

Week 13

Group	Value	95% CI
GSK2130579A Group	22

Week 15

Group	Value	95% CI
GSK2130579A Group	19

Week 21

Group	Value	95% CI
GSK2130579A Group	19

Week 32

Group	Value	95% CI
GSK2130579A Group	17

Week 40

Group	Value	95% CI
GSK2130579A Group	16

Week 54

Group	Value	95% CI
GSK2130579A Group	14

Number of Patients With Any Unsolicited Adverse Events Secondary · Within the 31-day (Days 0-30) post-administration period

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.

Group	Value	95% CI
GSK2130579A Group	33

Number of Patients With Any Serious Adverse Events (SAEs) Secondary · During the whole study duration (From Day 0 up to the concluding visit, at Month 49)

Serious adverse events (SAEs) assessed include any medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. 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 Clinical Report Form (CRF), but not as an SAE.

Group	Value	95% CI
GSK2130579A Group	8

Number of Patients With Serious Adverse Events Related to Study Treatment Secondary · During the whole study duration (From Day 0 up to the concluding visit, at Month 49)

Serious adverse events (SAEs) assessed include medical occurrences related to treatment administration that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. 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.

Group	Value	95% CI
GSK2130579A Group	3

Adverse events — posted to ClinicalTrials.gov

Time frame: Unsolicited adverse events (AEs): during the 31-day (Days 0-30) post-administration period; Serious adverse events (SAEs): during the entire study period (from Month 0 up to Month 49).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

GSK2130579A Group

Serious: 8/34 (24%)

Deaths: 5/34

Serious adverse events (14 terms)

Reaction	System	GSK2130579A Group
Thrombocytopenia	Blood and lymphatic system disorders	—
Myocardial infarction	Cardiac disorders	—
Abdominal pain	Gastrointestinal disorders	—
Oesophagitis	Gastrointestinal disorders	—
Small intestinal obstruction	Gastrointestinal disorders	—
Hypersensitivity	Immune system disorders	—
Encephalitis	Infections and infestations	—
Pneumonia	Infections and infestations	—
Upper respiratory tract infection	Infections and infestations	—
Viral infection	Infections and infestations	—
Wound infection	Infections and infestations	—
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Anxiety	Psychiatric disorders	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—

Other adverse events (78 terms — click to expand)

Reaction	System	GSK2130579A Group
Injection site pain	General disorders	—
Fatigue	General disorders	—
Dizziness	Nervous system disorders	—
Thrombocytopenia	Blood and lymphatic system disorders	—
Diarrhoea	Gastrointestinal disorders	—
Upper respiratory tract infection	Infections and infestations	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—
Constipation	Gastrointestinal disorders	—
Nausea	Gastrointestinal disorders	—
Back pain	Musculoskeletal and connective tissue disorders	—
Pain	General disorders	—
Leukopenia	Blood and lymphatic system disorders	—
Neutropenia	Blood and lymphatic system disorders	—
Injection site reaction	General disorders	—
Oedema peripheral	General disorders	—
Arthralgia	Musculoskeletal and connective tissue disorders	—
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	—
Dry skin	Skin and subcutaneous tissue disorders	—
Pruritus	Skin and subcutaneous tissue disorders	—
Abdominal pain	Gastrointestinal disorders	—
Influenza like illness	General disorders	—
Injection site erythema	General disorders	—
Pyrexia	General disorders	—
Aspartate aminotransferase increased	Investigations	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	—
Insomnia	Psychiatric disorders	—
Cough	Respiratory, thoracic and mediastinal disorders	—
Sinus congestion	Respiratory, thoracic and mediastinal disorders	—
Erythema	Skin and subcutaneous tissue disorders	—
Rash	Skin and subcutaneous tissue disorders	—
Anaemia	Blood and lymphatic system disorders	—
Vomiting	Gastrointestinal disorders	—
Asthenia	General disorders	—
Injection site pruritus	General disorders	—
Decreased appetite	Metabolism and nutrition disorders	—
Hypokalaemia	Metabolism and nutrition disorders	—
Myalgia	Musculoskeletal and connective tissue disorders	—
Anxiety	Psychiatric disorders	—
Chills	General disorders	—

Most-reported serious reactions: Thrombocytopenia, Myocardial infarction, Abdominal pain, Oesophagitis, Small intestinal obstruction, Hypersensitivity, Encephalitis, Pneumonia.

Data from ClinicalTrials.gov NCT00725283 adverse events section.

Sponsor's own description

This study is being done to evaluate the safety of a WT1 Antigen-Specific Cancer Immunotherapeutic (WT1 ASCI) as post-consolidation therapy in adult patients with WT1-positive Acute Myeloid Leukemia in first complete remission. It will also be analyzed to what extent this treatment induces an immune response, specific to the malignancy.

Publications & conference data

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

1. 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
2. Evaluation of current cancer immunotherapy: hemato-oncology.
   Hourigan CS, Levitsky HI. · · 2011 · cited 18× · PMID 21952281 · DOI 10.1097/ppo.0b013e3182341fde