Clinical trial NCT00725283: Evaluation of a New Anti-cancer Immunotherapy After Chemotherapy in Adult Patients With Acute Myeloid Leukemia (AML)
Official title: Study of GSK2130579A Tumor-Antigen-Specific Cancer Immunotherapeutic as Post-consolidation Therapy in Adult Patients With Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukaemia, Myelocytic, Acute
Keywords: Leukemia
ASCI
Complete remission
Immunotherapy
adult
Acute Myeloid Leukemia
Tumor antigen
WT1
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-07-30
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Patients With Severe Toxicities
timeFrame: During the study treatment period (From Day 0 to Month 48)
measure: Seropositivity Rates for Anti-Wilms Tumor Antigen 1 (WT1) Antibodies
timeFrame: 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]
measure: Concentrations for Anti-WT1 Antibodies
timeFrame: 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]
measure: Number of Patients With Anti-WT1 Antibody Response
timeFrame: 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:
measure: Number of Patients With Any Unsolicited Adverse Events
timeFrame: Within the 31-day (Days 0-30) post-administration period
measure: Number of Patients With Any Serious Adverse Events (SAEs)
timeFrame: During the whole study duration (From Day 0 up to the concluding visit, at Month 49)
measure: Number of Patients With Serious Adverse Events Related to Study Treatment
timeFrame: During the whole study duration (From Day 0 up to the concluding visit, at Month 49)
Other outcomes:
Locations:
city: Tampa
country: United States
facility: GSK Investigational Site
state: Florida
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Worcester
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Buffalo
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Winston-Salem
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Grenoble cedex 9
country: France
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: