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

Study of GSK2130579A Tumor-Antigen-Specific Cancer Immunotherapeutic in Adult Acute Myeloid Leukemia Patients With a Suboptimal Clinical Response to Induction Chemotherapy

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.

At least 40 patients will be enrolled in this study, divided in two cohorts of 20 patients each. One cohort will include patients in partial remission after induction therapy and one cohort will include patients in complete remission but with incomplete blood count recovery. Patients in both cohorts will receive the same study treatment according to the same administration schedule.

This protocol summary has been updated according to the Protocol Amendment 3 (dated 10 Sept 2014).

All active follow-up visits and procedures after the concluding visit, 30 days after the last treatment administration, will be stopped 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.

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.