Evaluation of a New Anti-cancer Immunotherapy in Adult Acute Myeloid Leukemia Patients With a Suboptimal Clinical Response to Induction Chemotherapy
Condition: Leukaemia, Myelocytic, Acute
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2130579A
Intervention description: Intramuscular injection
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: adult; WT1; ASCI; complete remission with incomplete blood count recovery; partial remission; post-induction therapy; tumor antigen; Acute Myeloid Leukemia; Immunotherapy

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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.

          -  The clinical status of the patient at inclusion is one of the following:

               -  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.

               -  Calculated creatinine clearance > 50 mL/min.

          -  In the view of the investigator, the patient can and will comply with the requirements
             of the protocol.

          -  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, then she must practice adequate contraception for 30 days
             prior to treatment administration, have a negative pregnancy test and continue such
             precautions for 2 months after completion of the treatment administration series.

        Exclusion Criteria:

          -  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.

          -  For female patients: the patient is pregnant or lactating.