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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01051063
First received: December 8, 2009
Last updated: July 3, 2014
Last verified: June 2014
  Purpose

This study is being done 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 Acute Myeloid Leukemia and with a suboptimal clinical response to induction chemotherapy. It will also be analyzed to what extent this treatment induces a specific immune response specific to the malignancy.

This protocol posting has been updated following Protocol amendment 1, Sep 2009.


Condition Intervention Phase
Leukaemia, Myelocytic, Acute
Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2130579A
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Study of GSK2130579A Tumor-Antigen-Specific Cancer Immunotherapeutic in Adult Acute Myeloid Leukemia Patients With a Suboptimal Clinical Response to Induction Chemotherapy

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Occurrence of severe toxicities as defined in the protocol [ Time Frame: During the study treatment period ] [ Designated as safety issue: No ]
  • Clinical activity [ Time Frame: At several defined timepoints during the whole study, including the follow-up period ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • immunogenicity of the WT1 ASCI [ Time Frame: At 21 defined timepoints during the whole study, including the follow-up period. ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: 1. Occurrence of adverse events (AE) and serious adverse events (SAE) during the study treatment period and ending 30 days after the last study treatment administration; 2. Occurence of SAE related to study treatment during the whole study duration ] [ Designated as safety issue: No ]
  • Clinical activity (other indicators) [ Time Frame: During the whole study, including the follow-up period ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: December 2009
Estimated Study Completion Date: January 2023
Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A
Not Applicable.
Biological: GSK Biologicals' recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) GSK2130579A
i.m. administration
Other Name: WT1 ASCI

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The patient has cytologically proven AML, as defined by the 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 RT-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 70 days (ten weeks) after the last chemotherapy 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 (as defined by "Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia" [Cheson, 2003]):
  • Partial Remission (PR) i.e.
  • A decrease of at least 50% in the percentage of blasts to 5% - 25% in the bone marrow aspirate following chemotherapy.
  • In case the bone marrow contains <= 5% blasts, the presence of Auer rods also indicates a partial remission.
  • Neutrophil count >= 1,000/μl
  • Platelet count >= 100,000/μl
  • The patient is independent of red blood cell transfusions
  • Morphologic complete remission with incomplete blood count recovery (CRi) i.e. patients fulfil all criteria of the morphological CR except for:
  • Neutrophil count <1,000/μl. and/or
  • Platelet count <= 100,000/μl. However, for the purpose of this clinical protocol platelet levels must be > 50,000/μl.
  • 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 at the time of enrolment.
  • Adequate hepatic and renal function defined as:
  • Serum bilirubin < 1.5 times the Upper Limit of Normal (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, 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, is receiving -or is due to receive- allogeneic SCT.
  • The patient has received Fludarabine, Clofarabine or Cloretazine within 12 months preceding the ASCI treatment.
  • 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 inflammatory 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 problems, 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 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 trial procedures.
  • The patient has received any investigational or non-registered medicinal product other than the study treatment 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 immunosuppressive agents.
  • Note: 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 is receiving full dose subcutaneous heparins or is under anti-coagulation treatment (e.g. phenprocoumon).
  • For female patients: the patient is pregnant or lactating.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01051063

Locations
United States, Maryland
GSK Investigational Site
Baltimore, Maryland, United States, 21201
United States, Massachusetts
GSK Investigational Site
Worcester, Massachusetts, United States, 01655
United States, Tennessee
GSK Investigational Site
Nashville, Tennessee, United States, 37232
France
GSK Investigational Site
Angers cedex 09, France, 49933
GSK Investigational Site
Grenoble cedex 9, France, 38043
GSK Investigational Site
Lille, France, 59037
GSK Investigational Site
Marseille cedex 9, France, 13273
GSK Investigational Site
Nantes cedex 1, France, 44093
GSK Investigational Site
Paris, France, 75010
GSK Investigational Site
Pessac cedex, France, 33604
GSK Investigational Site
Pierre-Bénite cedex, France, 69495
Germany
GSK Investigational Site
Freiburg, Baden-Wuerttemberg, Germany, 79106
GSK Investigational Site
Heidelberg, Baden-Wuerttemberg, Germany, 69120
GSK Investigational Site
Ulm, Baden-Wuerttemberg, Germany, 89081
GSK Investigational Site
Erlangen, Bayern, Germany, 91054
GSK Investigational Site
Wuerzburg, Bayern, Germany, 97080
GSK Investigational Site
Rostock, Mecklenburg-Vorpommern, Germany, 18057
GSK Investigational Site
Oldenburg, Niedersachsen, Germany, 26133
GSK Investigational Site
Muenster, Nordrhein-Westfalen, Germany, 48149
GSK Investigational Site
Mainz, Rheinland-Pfalz, Germany, 55131
GSK Investigational Site
Dresden, Sachsen, Germany, 01307
GSK Investigational Site
Berlin, Germany, 12200
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01051063     History of Changes
Other Study ID Numbers: 111727
Study First Received: December 8, 2009
Last Updated: July 3, 2014
Health Authority: France: Agence Française de Sécurité Sanitaire des Produits de Santé
Germany: Paul-Ehrlich-Institut
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
adult
WT1
ASCI
complete remission with incomplete blood count recovery
leukemia
partial remission
post-induction therapy
tumor antigen
Immunotherapy

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on July 29, 2014