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

NCT00725283 | Completed Phase 1 Results DMC

• 2 other identifiers: 1114442010-023886-24
• Study Type: interventional
• Target: 34
• Locations: 2 countries
• Sites: 10

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.

Conditions

Leukaemia, Myelocytic, Acute

Keywords

Leukemia; ASCI; Complete remission; Immunotherapy; adult; Acute Myeloid Leukemia; Tumor antigen; WT1

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (3)

• Number of Patients With Any Unsolicited Adverse Events

  Within the 31-day (Days 0-30) post-administration period

• 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)

• 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)

Study Arms (1)

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.

Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI)

Interventions

GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) BIOLOGICAL

Intramuscular administration

Also known as: WT1 ASCI, GSK2130579A

GSK2130579A Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (10)

GSK Investigational Site

Tampa, Florida, 33612, United States

Location

GSK Investigational Site

Baltimore, Maryland, 21201, United States

Location

GSK Investigational Site

Worcester, Massachusetts, 01655, United States

Location

GSK Investigational Site

Buffalo, New York, 14263, United States

Location

GSK Investigational Site

New York, New York, 10032, United States

Location

GSK Investigational Site

Winston-Salem, North Carolina, 27157-1009, United States

Location

GSK Investigational Site

Nashville, Tennessee, 37232, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229, United States

Location

GSK Investigational Site

Seattle, Washington, 98109-1023, United States

Location

GSK Investigational Site

Grenoble, 38043, France

Location

MeSH Terms

Conditions

Leukemia; Pathologic Complete Response; Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Progression; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myeloid

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2008
• First Posted: July 30, 2008
• Study Start: October 1, 2008
• Primary Completion: June 22, 2016
• Study Completion: June 22, 2016
• Last Updated: August 7, 2018
• Results First Posted: August 7, 2018

Record last verified: 2017-06

Locations

US (9); FR (1)