Leukaemia, Myelocytic, AcutePhase 1NCT00725283
Evaluation of a New Anti-cancer Immunotherapy After Chemotherapy in Adult Patients With Acute Myeloid Leukemia (AML)
A Phase 1 study testing GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) in people with Leukaemia, Myelocytic, Acute, run by GlaxoSmithKline at 10 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukaemia, Myelocytic, Acute
- What is being tested?
- GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 10 sitesin 2 countries
- Study dates
- 1 Oct 2008to 22 Jun 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
United States9 sites
GSK Investigational Site
Baltimore, Maryland, 21201
GSK Investigational Site
Buffalo, New York, 14263
GSK Investigational Site
Nashville, Tennessee, 37232
GSK Investigational Site
New York, New York, 10032
GSK Investigational Site
San Antonio, Texas, 78229
GSK Investigational Site
Seattle, Washington, 98109-1023
GSK Investigational Site
Tampa, Florida, 33612
GSK Investigational Site
Winston-Salem, North Carolina, 27157-1009
GSK Investigational Site
Worcester, Massachusetts, 01655
About this study
Official title: Study of GSK2130579A Tumor-Antigen-Specific Cancer Immunotherapeutic as Post-consolidation Therapy in Adult Patients With Acute Myeloid Leukemia
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.
Read the 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.
- Conditions
- Leukaemia, Myelocytic, Acute
- Being tested
- GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI)
- Keywords
- Leukemia, ASCI, Complete remission, Immunotherapy, adult, Acute Myeloid Leukemia, Tumor antigen, WT1
- Medical subject headings
- Leukemia, Pathologic Complete Response, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI)Biological
Also called WT1 ASCI, GSK2130579A
Intramuscular administration
| Study group | Role | What they receive |
|---|---|---|
| GSK2130579A Group | Experimental | 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. Receives: Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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 outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: During the whole study duration (From Day 0 up to the concluding visit, at Month 49)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2008 (estimated)
- Study start1 Oct 2008
- Primary completion22 Jun 2016
- Study completion22 Jun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Leukaemia, Myelocytic, AcuteStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00725283
- Sponsor's protocol ID
- 111444
- Other IDs
- 2010-023886-24
- Status last verified
- Jun 2017
- First submitted
- 29 Jul 2008
- Last updated
- 7 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of GSK2130579A Tumor-Antigen-Specific Cancer Immunotherapeutic as Post-consolidation Therapy in Adult Patients With Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT00725283
- Acronym / sponsor ID
- 111444
- Conditions
- Leukaemia, Myelocytic, Acute
- Keywords
- Leukemia, ASCI, Complete remission, Immunotherapy, adult, Acute Myeloid Leukemia, Tumor antigen, WT1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 1 Oct 2008 (actual)
- Primary completion
- 22 Jun 2016 (actual)
- Study completion
- 22 Jun 2016 (actual)
- First posted
- 30 Jul 2008 (estimated)
- Results
- Posted 7 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GSK2130579A Group | Experimental | Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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, …):
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI)Also: WT1 ASCI, GSK2130579AIntramuscular administration | Biological | GSK2130579A Group |
Primary outcome
Number of Patients With Severe Toxicities
Time frame: 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).
Seropositivity Rates for Anti-Wilms Tumor Antigen 1 (WT1) Antibodies
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]
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).
Concentrations for Anti-WT1 Antibodies
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]
Antibody concentrations were presented as geometric mean concentrations (GMCs) and expressed as ELISA units per milliliter (EU/mL).
Number of Patients With Anti-WT1 Antibody Response
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]
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.
3 secondary outcomes
Number of Patients With Any Unsolicited Adverse Events
Time frame: Within the 31-day (Days 0-30) post-administration period
Number of Patients With Any Serious Adverse Events (SAEs)
Time frame: 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
Time frame: During the whole study duration (From Day 0 up to the concluding visit, at Month 49)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) in people with Leukaemia, Myelocytic, Acute, run by GlaxoSmithKline at 10 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients With Severe Toxicities (time frame: During the study treatment period (From Day 0 to Month 48)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2018.