Evaluation of a New Anti-cancer Immunotherapy in Adult Acute Myeloid Leukemia Patients With a Suboptimal Clinical Response to Induction Chemotherapy

NCT01051063 | Completed Phase 1 Results

• 2 other identifiers: 1117272008-005348-17
• Study Type: interventional
• Target: 17
• Locations: 3 countries
• Sites: 22

Brief Summary

The purpose of this study is to evaluate the clinical activity and safety of a WT1 Antigen-Specific Cancer Immunotherapeutic (WT1 ASCI) as post-induction therapy in adult patients with WT1-positive AML presenting a suboptimal clinical response to induction chemotherapy. The study will also assess whether this treatment induces a specific immune response to the malignancy.

Conditions

Leukaemia, Myelocytic, Acute

Keywords

adult; WT1; ASCI; complete remission with incomplete blood count recovery; partial remission; post-induction therapy; tumor antigen; Acute Myeloid Leukemia; Immunotherapy

Outcome Measures

Primary Outcomes (2)

• 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: study product-related or possibly study product-related 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). * 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 entire study (from Month 0 to Month 49)

• Number of Patients With Best Overall Response, Defined by Either Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD)

  CR = having \< 5% blasts in aspirate sample with marrow spicules and with a count of ≥ 200 nucleated cells, no blasts with Auer rods or persistence of extramedullary disease; different phenotype (by flow cytometry) to the pre-treatment specimen; absolute neutrophil count \> 1000/mm3; platelet count ≥ 100 000/mm3 and being independent of red blood cell (RBC) transfusions. PR = a decrease of ≤ 50% in the % of blasts in bone marrow aspirate compared to Visit 4; being independent of RBC transfusions and the absolute neutrophil ≥ 1000/mm3 and platelet counts and ≥ 100 000/mm3. SD = no sufficient criteria for CR, a PR or Progressive disease (PD = Reappearance of leukemic blasts in the peripheral blood; Reappearance/development of cytologically proven extramedullary disease, Appearance of new dysplastic changes, or in a bone marrow aspirate sample (with marrow spicules and with a count of ≥200 nucleated cells) of ≥5% blasts; or, in case of early progression, a higher blast % than at Visit 4).

  During the entire study (from Month 0 to Month 49)

Secondary Outcomes (7)

• Anti-WT1 Seropositivity Rate

  At baseline (PRE), weeks (W) 5, 9, 13, 15, 21, 32, 40, 54, at months 15, 18, 21, 24, 30, 36, 42 and 49 (concluding visit), as well as follow-up visits 1 to 4

• Anti-WT1 Antibody Concentrations

  At baseline (PRE), weeks (W) 5, 9, 13, 15, 21, 32, 40, 54, at months 15, 18, 21, 24, 30, 36, 42 and 49 (concluding visit), as well as follow-up visits 1 to 4

• Anti-WT1 Antibody Response

  At baseline (PRE), weeks (W) 5, 9, 13, 15, 21, 32, 40, 54, at months 15, 18, 21, 24, 30, 36, 42 and 49 (concluding visit), as well as follow-up visits 1 to 4

• Number of Subjects With Any and Related Unsolicited Adverse Events (AEs)

  Starting with the first administration of study treatment and ending 30 days after the last study treatment administration

• Number of Subjects With Study Treatment Failure

  During the entire study (from Month 0 to Month 49)

Study Arms (2)

Partial Remission Group

EXPERIMENTAL

Adult patients in partial remission post-induction chemotherapy, who received the GSK2130579A study product, administered sequentially, as follows: Cycle 1: 6 doses, each given at 2-week intervals; Cycle 2: 6 doses, each given at 3-week intervals; Cycle 3: 4 doses, each given at 6-week intervals; Cycle 4: 4 doses, each given at 3-month intervals, followed by 4 doses each given at 6-month intervals.

Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2130579A

Complete Remission Group

EXPERIMENTAL

Adult patients in complete remission with incomplete blood count recovery post-induction chemotherapy, who received the GSK2130579A study product, administered sequentially, as follows: Cycle 1: 6 doses, each given at 2-week intervals; Cycle 2: 6 doses, each given at 3-week intervals; Cycle 3: 4 doses, each given at 6-week intervals; Cycle 4: 4 doses, each given at 3-month intervals, followed by 4 doses each given at 6-month intervals.

Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2130579A

Interventions

GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2130579A BIOLOGICAL

Intramuscular injection

Also known as: WT1 ASCI

Complete Remission Group; Partial Remission 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 World Health Organization (WHO) classification. The pretreatment AML karyotype should be documented.
• The leukemia is a de novo or secondary AML.
• The patient's blasts cells show expression of WT1 transcript, detected by quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR).The patient received the following therapy according to the Institution's standard of care.
• For patients \< 60 years old: at least two induction chemotherapy treatments.
• For patients \>= 60 years old: at least one induction chemotherapy treatment or alternative treatment.
• The first ASCI administration should be given within one year after the last chemotherapy administration. All screening procedures should be completed within seven weeks before the first ASCI administration.
• In the investigator's opinion and in compliance with the Institution Hematology Tumor Board's guidances, the patient should not be eligible for any additional chemotherapy treatment before the ASCI treatment.
• Partial Remission (PR)
• Morphologic complete remission with incomplete blood count recovery (CRi)
• 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 first 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 ALT \< 2.5 times the ULN.

You may not qualify if:

• The patient was diagnosed with leukemic Central Nervous System (CNS) disease (e.g. before chemotherapy) or presents neurological symptoms at baseline suggestive of a CNS involvement.
• The patient has acute promyelocytic leukemia with t(15;17) (q22;q12), (PML/RARα) or variants.
• The patient has received, or is receiving, allogeneic Stem Cell Transplantation (SCT).
• The patient has received Fludarabine, Clofarabine or Cloretazine within 12 months preceding the ASCI treat-ment.
• 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. Patients with vitiligo are not excluded.
• 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 another metastatic cancer disease.
• The patient has a history of congestive heart failure, coronary 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 treat-ment within 30 days preceding the first dose of study treatment or plans to receive such a drug during the study period.
• The patient requires concomitant chronic treatment (more than 7 consecutive days) with systemic corticosteroids or any other immunosuppressive agents.
• The patient is receiving full dose subcutaneous heparins or is under anti-coagulation treatment.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (22)

GSK Investigational Site

Baltimore, Maryland, 21201, United States

Location

GSK Investigational Site

Worcester, Massachusetts, 01655, United States

Location

GSK Investigational Site

Nashville, Tennessee, 37232, United States

Location

GSK Investigational Site

Angers, 49933, France

Location

GSK Investigational Site

Grenoble, 38043, France

Location

GSK Investigational Site

Lille, 59037, France

Location

GSK Investigational Site

Marseille, 13273, France

Location

GSK Investigational Site

Nantes, 44093, France

Location

GSK Investigational Site

Paris, 75475, France

Location

GSK Investigational Site

Pessac, 33604, France

Location

GSK Investigational Site

Pierre-Bénite, 69495, France

Location

GSK Investigational Site

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

GSK Investigational Site

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

GSK Investigational Site

Ulm, Baden-Wurttemberg, 89081, Germany

Location

GSK Investigational Site

Erlangen, Bavaria, 91054, Germany

Location

GSK Investigational Site

Würzburg, Bavaria, 97080, Germany

Location

GSK Investigational Site

Oldenburg, Lower Saxony, 26133, Germany

Location

GSK Investigational Site

Rostock, Mecklenburg-Vorpommern, 18057, Germany

Location

GSK Investigational Site

Münster, North Rhine-Westphalia, 48149, Germany

Location

GSK Investigational Site

Mainz, Rhineland-Palatinate, 55131, Germany

Location

GSK Investigational Site

Dresden, Saxony, 01307, Germany

Location

GSK Investigational Site

Berlin, 12200, Germany

Location

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; 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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2009
• First Posted: January 18, 2010
• Study Start: December 9, 2009
• Primary Completion: April 26, 2016
• Study Completion: April 26, 2016
• Last Updated: November 29, 2018
• Results First Posted: November 29, 2018

Record last verified: 2018-06

Locations

US (3); DE (11); FR (8)