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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Study of GSK2130579A Tumor-Antigen-Specific Cancer Immunotherapeutic as Post-consolidation Therapy in Adult Patients With Acute Myeloid Leukemia

Conditions
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Leukaemia, Myelocytic, Acute

Intervention / Treatment
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* Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK2130579A Group<br>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)<br>* Intramuscular administration<br>* Other names: GSK2130579A;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Severe Toxicities | 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). | During the study treatment period (From Day 0 to Month 48) | 
| Seropositivity Rates for Anti-Wilms Tumor Antigen 1 (WT1) Antibodies | 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). | 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] | 
| Concentrations for Anti-WT1 Antibodies | Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed as ELISA units per milliliter (EU/mL). | 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] | 
| Number of Patients With Anti-WT1 Antibody Response | 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. | 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] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Any Unsolicited Adverse Events | 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. | Within the 31-day (Days 0-30) post-administration period | 
| Number of Patients With Any Serious Adverse Events (SAEs) | 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. | During the whole study duration (From Day 0 up to the concluding visit, at Month 49) | 
| Number of Patients With Serious Adverse Events Related to Study Treatment | 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. | During the whole study duration (From Day 0 up to the concluding visit, at Month 49) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leukemia, ASCI, Complete remission, Immunotherapy, adult, Acute Myeloid Leukemia, Tumor antigen, WT1