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

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00725283
• Collaborator: (none)
• Enrollment: 34
• Locations: 10
• Arm: 1
• Actual Duration (Months): 92.7
• Patients Per Site: 3.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Leukaemia, Myelocytic, Acute	Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI)	Phase 1

Detailed Description

In this study, patients were to receive a maximum of 24 doses of WT1 ASCI according four cycles over a period of four years.

This protocol summary has been updated according to the Protocol Amendment 6 (dated 10 Sept 2014).

There will no longer be an active follow-up of patients after discontinuation or completion of the treatment. The study will end 30 days after the last dose will be administered, so the patients will not be further exposed to unnecessary study related procedures.. In addition, no more biological samples will be collected for protocol research purposes. For each biological sample already collected in the scope of this study and not tested yet, testing will not be performed by default, except if a scientific rationale remains relevant. Blood sampling for safety monitoring as per protocol will continue.

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Study of GSK2130579A Tumor-Antigen-Specific Cancer Immunotherapeutic as Post-consolidation Therapy in Adult Patients With Acute Myeloid Leukemia
• Actual Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Jun 22, 2016
• Actual Study Completion Date: Jun 22, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GSK2130579A Group Patients with cytologically proven AML, as defined by the World Health Organization classification, who were administered a standard dose of GSK2130579A treatment. Patients received 24 doses of the study treatment over a period of approximately 4 years.	Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI); Intramuscular administration; Other Names: WT1 ASCI GSK2130579A

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Severe Toxicities [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 toxicity (i.e., rash, flushing, urticaria, and dyspnea). Drug fever was not part of this definition. Decrease in renal function, with a calculated creatinine clearance < 40 mL/min. Grade 2 cardiac ischemia/infarction (i.e., asymptomatic and testing suggesting ischemia; stable angina).

2. Seropositivity Rates for Anti-Wilms Tumor Antigen 1 (WT1) Antibodies [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).

3. Concentrations for Anti-WT1 Antibodies [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).

4. Number of Patients With Anti-WT1 Antibody Response [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.

Secondary Outcome Measures

1. Number of Patients With Any Unsolicited Adverse Events [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.

2. Number of Patients With Any Serious Adverse Events (SAEs) [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.

3. Number of Patients With Serious Adverse Events Related to Study Treatment [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The patient has cytologically proven AML, as defined by the WHO classification. The pretreatment AML karyotype should be documented.

• The leukemia could be a de novo or secondary AML.

• The patient received induction and consolidation therapy according to the Institution's standard of care.

• The patient's blasts cells show expression of WT1 tran-script, detected by quantitative RT-PCR.

• The patient is in complete remission (i.e. CR1, CR2, …):

• Written informed consent has been obtained prior to the performance of any protocol-specific procedure.

• The patient is >= 18 years of age at the time of signature of the informed consent form.

• Eastern Cooperative Oncology Group performance status of 0, 1 or 2.

• Adequate hepatic and renal function defined as:

• Serum bilirubin < 1.5 times the Upper Limit of Nor-mal (ULN).

• Serum alanine aminotransferase < 2.5 times the ULN.

• Calculated creatinine clearance > 50 mL/min.

• If the patient is female, she must be of non-childbearing potential, i.e. have a current tubal ligation, hysterectomy, ovariectomy or be post-menopausal, or if she is of childbearing potential, she must practice adequate con-traception for 30 days prior to treatment administration, have a negative pregnancy test and continue such pre-cautions for two months after completion of the treatment administration series.

• In the view of the investigator, the patient can and will comply with the requirements of the protocol.

Exclusion Criteria:

• The patient is in morphologic leukemia-free state or in morphologic complete remission with incomplete blood count recovery (CRi).

• The patient has acute promyelocytic leukemia with t(15;17)(q22;q12), (PML/RARα) or variants.

• The patient has received, or is receiving induction chemotherapy followed by Stem Cell Transplantation.

• The patient has (or has had) previous or concomitant malignancies, except effectively treated malignancy that is considered by the investigator highly likely to have been cured.

• The patient has hypercalcemia.

• The patient is known to be HIV-positive.

• The patient has symptomatic autoimmune disease such as, but not limited to multiple sclerosis, lupus, and in-flammatory bowel disease.

• The patient has a history of allergic reactions likely to be exacerbated by any component of the study investigational product.

• The patient has other concurrent severe medical prob-lems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk.

• The patient has a history of congestive heart failure, cor-onary artery disease or previous myocardial infarction.

• The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with the study procedures.

• The patient has received any investigational or non-registered medicinal product other than the study medi-cation within 30 days preceding the first dose of study medication or plans to receive such a drug during the study period.

• The patient requires concomitant treatment with systemic corticosteroids or any other immunosuppressive agents. The use of prednisone, or equivalent, <0.5 mg/kg/day (absolute maximum 40 mg/day), or inhaled corticosteroids or topical steroids is permitted.

• The patient has received intravenous administration of antibiotics within 2 weeks prior to first study treatment or oral antibiotics within 1 week prior to first study treatment.

• For female patients: the patient is pregnant or lactating.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Tampa	Florida	United States	33612
2	GSK Investigational Site	Baltimore	Maryland	United States	21201
3	GSK Investigational Site	Worcester	Massachusetts	United States	01655
4	GSK Investigational Site	Buffalo	New York	United States	14263
5	GSK Investigational Site	New York	New York	United States	10032
6	GSK Investigational Site	Winston-Salem	North Carolina	United States	27157-1009
7	GSK Investigational Site	Nashville	Tennessee	United States	37232
8	GSK Investigational Site	San Antonio	Texas	United States	78229
9	GSK Investigational Site	Seattle	Washington	United States	98109-1023
10	GSK Investigational Site	Grenoble cedex 9		France	38043

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00725283
• Other Study ID Numbers: 111444; 2010-023886-24
• First Posted: Jul 30, 2008
• Last Update Posted: Aug 7, 2018
• Last Verified: Jun 1, 2017

• Keywords provided by GlaxoSmithKline: Leukemia; ASCI; Complete remission; Immunotherapy; adult; Acute Myeloid Leukemia; Tumor antigen; WT1
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute

Study Results

Participant Flow

Arm/Group Title	GSK2130579A Group
Arm/Group Description	Patients with cytologically proven Acute Myeloid Leukemia (AML), as defined by the World Health Organization classification, who were administered a standard dose of GSK2130579A treatment. Patients received 24 doses of the study treatment over a period of approximately 4 years, administered in 4 cycles (Cycle 1: 6 doses, given at 2-week intervals; Cycle 2: 6 doses, given at 3-week intervals; Cycle 3: 4 doses, given at 6-week intervals; Cycle 4: 4 doses, given at 3-month intervals followed by other 4 doses, given at 6-month intervals).
Period Title: Overall Study
STARTED	34
COMPLETED	10
NOT COMPLETED	24

Baseline Characteristics

Arm/Group Title	GSK2130579A Group
Arm/Group Description	Patients with cytologically proven Acute Myeloid Leukemia (AML), as defined by the World Health Organization classification, who were administered a standard dose of GSK2130579A treatment. Patients received 24 doses of the study treatment over a period of approximately 4 years, administered in 4 cycles (Cycle 1: 6 doses, given at 2-week intervals; Cycle 2: 6 doses, given at 3-week intervals; Cycle 3: 4 doses, given at 6-week intervals; Cycle 4: 4 doses, given at 3-month intervals followed by other 4 doses, given at 6-month intervals).
Overall Participants	34
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	60.1 (12.3)
Sex: Female, Male (Count of Participants)
Female	18 52.9%
Male	16 47.1%
Race and Ethnicity Not Collected (Count of Participants)

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Severe Toxicities
Description	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 toxicity (i.e., rash, flushing, urticaria, and dyspnea). Drug fever was not part of this definition. Decrease in renal function, with a calculated creatinine clearance < 40 mL/min. Grade 2 cardiac ischemia/infarction (i.e., asymptomatic and testing suggesting ischemia; stable angina).
Time Frame	During the study treatment period (From Day 0 to Month 48)

Outcome Measure Data

Analysis Population Description

This analysis was performed on the Total treated population, which included all patients who had started treatment and received at least one dose of the study product, which were included in the overall safety analyses.

Arm/Group Title	GSK2130579A Group
Arm/Group Description	Patients with cytologically proven Acute Myeloid Leukemia (AML), as defined by the World Health Organization classification, who were administered a standard dose of GSK2130579A treatment. Patients received 24 doses of the study treatment over a period of approximately 4 years, administered in 4 cycles (Cycle 1: 6 doses, given at 2-week intervals; Cycle 2: 6 doses, given at 3-week intervals; Cycle 3: 4 doses, given at 6-week intervals; Cycle 4: 4 doses, given at 3-month intervals followed by other 4 doses, given at 6-month intervals).
Measure Participants	34
Encephalitis	1 2.9%
Rash erythematous	1 2.9%
Hypersensitivity	1 2.9%
Angina pectoris	1 2.9%
Rash	1 2.9%
Thrombocytopenia	1 2.9%

2. Primary Outcome

Title	Seropositivity Rates for Anti-Wilms Tumor Antigen 1 (WT1) Antibodies
Description	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).
Time Frame	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]

Outcome Measure Data

Analysis Population Description

This analysis was performed on the Total treated population, which included all patients who had started treatment and received at least one dose of the study product, which were included in the overall safety analyses and for whom assay results were available at the considered timepoints.

Arm/Group Title	GSK2130579A Group
Arm/Group Description	Patients with cytologically proven Acute Myeloid Leukemia (AML), as defined by the World Health Organization classification, who were administered a standard dose of GSK2130579A treatment. Patients received 24 doses of the study treatment over a period of approximately 4 years, administered in 4 cycles (Cycle 1: 6 doses, given at 2-week intervals; Cycle 2: 6 doses, given at 3-week intervals; Cycle 3: 4 doses, given at 6-week intervals; Cycle 4: 4 doses, given at 3-month intervals followed by other 4 doses, given at 6-month intervals).
Measure Participants	31
Week 0	2 5.9%
Week 5	6 17.6%
Week 9	21 61.8%
Week 13	24 70.6%
Week 15	21 61.8%
Week 21	21 61.8%
Week 32	19 55.9%
Week 40	18 52.9%
Week 54	16 47.1%
Month 15	12 35.3%
Month 18	9 26.5%
Month 21	6 17.6%
Month 24	5 14.7%
Month 30	1 2.9%
Month 49	15 44.1%
Month 52	7 20.6%
Month 55	7 20.6%
Month 58	6 17.6%
Month 61	3 8.8%

3. Primary Outcome

Title	Concentrations for Anti-WT1 Antibodies
Description	Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed as ELISA units per milliliter (EU/mL).
Time Frame	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]

Outcome Measure Data

Analysis Population Description

This analysis was performed on the Total treated population, which included all patients who had started treatment and received at least one dose of the study product, which were included in the overall safety analyses and for whom assay results were available at the considered timepoints.

Arm/Group Title	GSK2130579A Group
Arm/Group Description	Patients with cytologically proven Acute Myeloid Leukemia (AML), as defined by the World Health Organization classification, who were administered a standard dose of GSK2130579A treatment. Patients received 24 doses of the study treatment over a period of approximately 4 years, administered in 4 cycles (Cycle 1: 6 doses, given at 2-week intervals; Cycle 2: 6 doses, given at 3-week intervals; Cycle 3: 4 doses, given at 6-week intervals; Cycle 4: 4 doses, given at 3-month intervals followed by other 4 doses, given at 6-month intervals).
Measure Participants	31
Week 0	4.8
Week 5	6.3
Week 9	145.3
Week 13	337.6
Week 15	313.4
Week 21	296.9
Week 32	285.3
Week 40	173.7
Week 54	174.9
Month 15	111.0
Month 18	111.3
Month 21	74.6
Month 24	76.7
Month 30	80.0
Month 49	45.3
Month 52	25.6
Month 55	18.7
Month 58	24.0
Month 61	25.5

4. Primary Outcome

Title	Number of Patients With Anti-WT1 Antibody Response
Description	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.
Time Frame	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]

Outcome Measure Data

Analysis Population Description

This analysis was performed on the Total treated population, which included all patients who had started treatment and received at least one dose of the study product, which were included in the overall safety analyses and for whom assay results were available at the considered timepoints.

Arm/Group Title	GSK2130579A Group
Arm/Group Description	Patients with cytologically proven Acute Myeloid Leukemia (AML), as defined by the World Health Organization classification, who were administered a standard dose of GSK2130579A treatment. Patients received 24 doses of the study treatment over a period of approximately 4 years, administered in 4 cycles (Cycle 1: 6 doses, given at 2-week intervals; Cycle 2: 6 doses, given at 3-week intervals; Cycle 3: 4 doses, given at 6-week intervals; Cycle 4: 4 doses, given at 3-month intervals followed by other 4 doses, given at 6-month intervals).
Measure Participants	25
Week 5	4 11.8%
Week 9	20 58.8%
Week 13	22 64.7%
Week 15	19 55.9%
Week 21	19 55.9%
Week 32	17 50%
Week 40	16 47.1%
Week 54	14 41.2%
Month 15	10 29.4%
Month 18	7 20.6%
Month 21	4 11.8%
Month 24	3 8.8%
Month 30	1 2.9%
Month 49	15 44.1%
Month 52	7 20.6%
Month 55	7 20.6%
Month 58	6 17.6%
Month 61	3 8.8%

5. Secondary Outcome

Title	Number of Patients With Any Unsolicited Adverse Events
Description	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.
Time Frame	Within the 31-day (Days 0-30) post-administration period

Outcome Measure Data

Analysis Population Description

This analysis was performed on the Total treated population, which included all patients who had started treatment and received at least one dose of the study product, which were included in the overall safety analyses.

Arm/Group Title	GSK2130579A Group
Arm/Group Description	Patients with cytologically proven Acute Myeloid Leukemia (AML), as defined by the World Health Organization classification, who were administered a standard dose of GSK2130579A treatment. Patients received 24 doses of the study treatment over a period of approximately 4 years, administered in 4 cycles (Cycle 1: 6 doses, given at 2-week intervals; Cycle 2: 6 doses, given at 3-week intervals; Cycle 3: 4 doses, given at 6-week intervals; Cycle 4: 4 doses, given at 3-month intervals followed by other 4 doses, given at 6-month intervals).
Measure Participants	34
Count of Participants [Participants]	33 97.1%

6. Secondary Outcome

Title	Number of Patients With Any Serious Adverse Events (SAEs)
Description	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.
Time Frame	During the whole study duration (From Day 0 up to the concluding visit, at Month 49)

Outcome Measure Data

Analysis Population Description

This analysis was performed on the Total treated population, which included all patients who had started treatment and received at least one dose of the study product, which were included in the overall safety analyses.

Arm/Group Title	GSK2130579A Group
Arm/Group Description	Patients with cytologically proven Acute Myeloid Leukemia (AML), as defined by the World Health Organization classification, who were administered a standard dose of GSK2130579A treatment. Patients received 24 doses of the study treatment over a period of approximately 4 years, administered in 4 cycles (Cycle 1: 6 doses, given at 2-week intervals; Cycle 2: 6 doses, given at 3-week intervals; Cycle 3: 4 doses, given at 6-week intervals; Cycle 4: 4 doses, given at 3-month intervals followed by other 4 doses, given at 6-month intervals).
Measure Participants	34
Count of Participants [Participants]	8 23.5%

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

This analysis was performed on the Total treated population, which included all patients who had started treatment and received at least one dose of the study product, which were included in the overall safety analyses.

Arm/Group Title	GSK2130579A Group
Arm/Group Description	Patients with cytologically proven Acute Myeloid Leukemia (AML), as defined by the World Health Organization classification, who were administered a standard dose of GSK2130579A treatment. Patients received 24 doses of the study treatment over a period of approximately 4 years, administered in 4 cycles (Cycle 1: 6 doses, given at 2-week intervals; Cycle 2: 6 doses, given at 3-week intervals; Cycle 3: 4 doses, given at 6-week intervals; Cycle 4: 4 doses, given at 3-month intervals followed by other 4 doses, given at 6-month intervals).
Measure Participants	34
Count of Participants [Participants]	3 8.8%

Adverse Events

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).
Arm/Group Title	GSK2130579A Group
Arm/Group Description	Patients with cytologically proven Acute Myeloid Leukemia (AML), as defined by the World Health Organization classification, who were administered a standard dose of GSK2130579A treatment. Patients received 24 doses of the study treatment over a period of approximately 4 years, administered in 4 cycles (Cycle 1: 6 doses, given at 2-week intervals; Cycle 2: 6 doses, given at 3-week intervals; Cycle 3: 4 doses, given at 6-week intervals; Cycle 4: 4 doses, given at 3-month intervals followed by other 4 doses, given at 6-month intervals).
All Cause Mortality
	GSK2130579A Group
	Affected / at Risk (%)	# Events
Total	5/34 (14.7%)
Serious Adverse Events
	GSK2130579A Group
	Affected / at Risk (%)	# Events
Total	8/34 (23.5%)
Blood and lymphatic system disorders
Thrombocytopenia	1/34 (2.9%)	1
Cardiac disorders
Myocardial infarction	1/34 (2.9%)	1
Gastrointestinal disorders
Abdominal pain	1/34 (2.9%)	1
Oesophagitis	1/34 (2.9%)	1
Small intestinal obstruction	1/34 (2.9%)	1
Immune system disorders
Hypersensitivity	1/34 (2.9%)	1
Infections and infestations
Encephalitis	1/34 (2.9%)	1
Pneumonia	1/34 (2.9%)	2
Upper respiratory tract infection	1/34 (2.9%)	1
Viral infection	1/34 (2.9%)	1
Wound infection	1/34 (2.9%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma	1/34 (2.9%)	1
Psychiatric disorders
Anxiety	1/34 (2.9%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/34 (2.9%)	1
Other (Not Including Serious) Adverse Events
	GSK2130579A Group
	Affected / at Risk (%)	# Events
Total	33/34 (97.1%)
Blood and lymphatic system disorders
Anaemia	4/34 (11.8%)	5
Increased tendency to bruise	2/34 (5.9%)	2
Leukopenia	6/34 (17.6%)	6
Lymphopenia	2/34 (5.9%)	2
Neutropenia	6/34 (17.6%)	7
Thrombocytopenia	10/34 (29.4%)	17
Gastrointestinal disorders
Abdominal pain	5/34 (14.7%)	6
Constipation	9/34 (26.5%)	10
Diarrhoea	10/34 (29.4%)	15
Dry mouth	2/34 (5.9%)	2
Nausea	9/34 (26.5%)	24
Vomiting	4/34 (11.8%)	7
General disorders
Asthenia	4/34 (11.8%)	6
Chills	3/34 (8.8%)	4
Cyst	2/34 (5.9%)	2
Fatigue	17/34 (50%)	40
Influenza like illness	5/34 (14.7%)	6
Injection site erythema	5/34 (14.7%)	7
Injection site pain	22/34 (64.7%)	78
Injection site pruritus	4/34 (11.8%)	13
Injection site reaction	6/34 (17.6%)	15
Injection site swelling	3/34 (8.8%)	4
Oedema peripheral	6/34 (17.6%)	11
Pain	7/34 (20.6%)	9
Pyrexia	5/34 (14.7%)	6
Infections and infestations
Bronchitis	3/34 (8.8%)	3
Herpes zoster	3/34 (8.8%)	3
Upper respiratory tract infection	10/34 (29.4%)	15
Urinary tract infection	2/34 (5.9%)	3
Injury, poisoning and procedural complications
Contusion	3/34 (8.8%)	3
Procedural pain	3/34 (8.8%)	4
Skin abrasion	2/34 (5.9%)	2
Investigations
Alanine aminotransferase increased	2/34 (5.9%)	3
Aspartate aminotransferase increased	5/34 (14.7%)	6
Metabolism and nutrition disorders
Decreased appetite	4/34 (11.8%)	5
Hyperglycaemia	3/34 (8.8%)	5
Hyperkalaemia	2/34 (5.9%)	3
Hypokalaemia	4/34 (11.8%)	6
Iron overload	2/34 (5.9%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	6/34 (17.6%)	10
Back pain	8/34 (23.5%)	9
Bone pain	2/34 (5.9%)	2
Muscle spasms	5/34 (14.7%)	5
Muscular weakness	2/34 (5.9%)	7
Musculoskeletal pain	5/34 (14.7%)	6
Musculoskeletal stiffness	2/34 (5.9%)	2
Myalgia	4/34 (11.8%)	6
Neck pain	3/34 (8.8%)	3
Pain in extremity	10/34 (29.4%)	19
Nervous system disorders
Dizziness	16/34 (47.1%)	25
Headache	3/34 (8.8%)	3
Hypoaesthesia	2/34 (5.9%)	2
Neuropathy peripheral	2/34 (5.9%)	2
Post herpetic neuralgia	2/34 (5.9%)	2
Sciatica	2/34 (5.9%)	2
Psychiatric disorders
Anxiety	4/34 (11.8%)	6
Insomnia	5/34 (14.7%)	6
Renal and urinary disorders
Haematuria	3/34 (8.8%)	3
Reproductive system and breast disorders
Breast pain	2/34 (5.9%)	2
Respiratory, thoracic and mediastinal disorders
Cough	5/34 (14.7%)	7
Dyspnoea	3/34 (8.8%)	3
Dyspnoea exertional	6/34 (17.6%)	7
Oropharyngeal pain	3/34 (8.8%)	3
Productive cough	2/34 (5.9%)	3
Rhinitis allergic	2/34 (5.9%)	3
Rhinorrhoea	2/34 (5.9%)	4
Sinus congestion	5/34 (14.7%)	9
Upper-airway cough syndrome	2/34 (5.9%)	3
Skin and subcutaneous tissue disorders
Dry skin	6/34 (17.6%)	7
Erythema	5/34 (14.7%)	8
Night sweats	2/34 (5.9%)	2
Onychoclasis	2/34 (5.9%)	4
Pruritus	6/34 (17.6%)	9
Rash	5/34 (14.7%)	5
Rash erythematous	3/34 (8.8%)	5
Skin lesion	2/34 (5.9%)	2
Vascular disorders
Hypertension	3/34 (8.8%)	3
Hypotension	2/34 (5.9%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.