Safety and Immunogenicity of Recombinant WT1 Antigen-Specific Cancer Immunotherapeutic Combined With Infusion of Treg Depleted T Cells for Adult WT1 Acute Myeloid Leukemia (ASCI)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2012 by Jules Bordet Institute
Sponsor:
Information provided by (Responsible Party):
Jules Bordet Institute
ClinicalTrials.gov Identifier:
NCT01513109
First received: January 16, 2012
Last updated: January 19, 2012
Last verified: January 2012
  Purpose

The purpose of this study is to evaluate the safety and the efficacy of combined treatment strategy of WT1ASCI, infusion of ex vivo regulatory T cells depleted T lymphocytes and in vivo regulatory T cells depletion as post-consolidation therapy in patients with WT1-positive Acute Myeloid Leukemia. The study will also evaluate the clinical activity and immune response of this approach in bad risk patients in CR1 and all patients in CR2 or CR3, non eligible for an allogeneic Hematopoietic Stem Cell Transplantation


Condition Intervention Phase
Acute Myelogenous Leukemia
Myeloid Leukemia in Remission
Effects of Immunotherapy
Biological: Recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study to Assess the Safety and Immunogenicity of WT1-A10 + AS01B Antigen-Specific Cancer Immunotherapeutic (ASCI) Combined With Infusions of ex Vivo Regulatory T Cells Depleted T Lymphocytes in in Vivo Regulatory T Cells Depleted Patients as Post-consolidation Therapy for Adult Patients With WT1-positive Acute Myeloid Leukemia (AML) in CR1 (for High Risk Patients) or in CR2 or CR3 Who Are Not Eligible for Allogeneic Stem Cell Transplantation (SCT).

Resource links provided by NLM:


Further study details as provided by Jules Bordet Institute:

Primary Outcome Measures:
  • Occurence of severe toxicities [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Immunogenicity of the WT1 ASCI [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: December 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment arm
Recombinant WT1 Antigen-Specific Cancer Immunotherapeutic combined with Treg depletion
Biological: Recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI)
i.m. administration

Detailed Description:

High-risk and intermediate-high risk CR1 AML patients who are not eligible for allo-SCT after chemotherapy have an unfavorable prognosis, and there is currently no treatment able to improve their survival. New approaches to treat these patients are thus urgently needed. Active immunization against tumor antigens is certainly one of these approaches. The tumor antigen targeted in this study is WT1, which is overexpressed and acts as an oncogene in leukemia and several types of solid tumors. WT1-positive acute myeloid Leukemia patients in complete remission (CR) will first undergo two cytaphereses, one of which being frozen, after CD25+ T cell depletion, the second, being frozen unmanipulated as a Treg back-up. Next, patients will be treated for 5 weeks with oral cyclophosphamide according to the so-called "metronomic regimen" to achieve in vivo Treg depletion. Patients will thereafter receive WT1 ASCI combined with CD25+ T cell depleted lymphocytes. The total duration of the treatment period will last 48 months (4 years).

  Eligibility

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

Inclusion Criteria:

  1. The patient has cytologically proven AML, as defined by the WHO classification. The leukemia is a de novo or a secondary leukemia.
  2. The patient is in complete morphologic remission Note: Cytogenetic CR (CRc) or molecular CR (CRm) is not required.

    • AML patients in first complete remission (CR1) who are not eligible for allo-HSCT following the institution's standard of care(except the favourable genetic group subset which is excluded from this study).
    • All AML patients in second or third complete morphological remission(CR2 or CR3) who are not eligible for allo-HSCT.
  3. The patient received the following therapy according to the institution's standard of care:

    • For patients ≤ 60 years old, at least two cycles of intensive chemotherapy (induction and consolidation)
    • For patients > 60 years old, at least one induction chemotherapy. Any patients with severe co-morbidity for which consolidation is unacceptable, can receive only one induction therapy.
  4. The patient's blasts cells show over-expression of WT1 transcripts, detected in peripheral blood by qRT-PCR at diagnosis or at first relapse.
  5. Written informed consent has been obtained prior to the performance of any protocol-specific procedure.
  6. The patient is ≥ 18 years of age at the time of signing of the ICF.
  7. ECOG performance status of 0, 1, or 2 at the time of enrollment.
  8. Adequate hepatic and renal function defined as:

    • Serum bilirubin < 1.5 times the Upper Limit of Normal (ULN).
    • Serum alanine aminotransferase ALAT < 2.5 times the ULN.
    • Calculated creatinine clearance > 40 mL/min.
  9. If the patient is female, then 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 two months after completion of the treatment administration series.
  10. Under the investigator criteria, the patient is able to comply with the protocol requirements during the duration of the study.
  11. In the investigator's opinion and in compliance with the Institution hematology guidance, the patient should not be eligible for an approved standard of care such as induction with chemotherapy or allo-HSCT.

Exclusion Criteria:

  1. The patient is in morphologic leukemia-free state or in morphologic complete remission but with incomplete blood count recovery as defined by IWG Response Criteria
  2. The patient is in CR1 and is in the category of low-risk for relapse patients, i.e. belong to the favourable genetic group subset .
  3. 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.
  4. The patient has received, is receiving (or is due to receive) allo-HSCT.
  5. The patient has (or has had) concomitant malignancies, except effectively treated malignancy that is considered by the investigator highly likely to have been cured.
  6. The patient is known to be human immunodeficiency virus (HIV)-positive.
  7. The patient has symptomatic autoimmune disease such as, but not limited to, multiple sclerosis, lupus, rheumatoid arthritis and inflammatory bowel disease.
  8. The patient has a history of allergic reactions likely to be exacerbated by any component of the study investigational product.
  9. 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.
  10. The patient has congestive heart failure, symptomatic coronary artery disease, or previous myocardial infarction.
  11. The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with the study procedures.
  12. The patient has received any investigational or non-registered medicinal product other than the study medication within 30 days preceding the first dose of study medication, or plans to receive such a drug during the study period.
  13. 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), inhaled corticosteroids or topical steroids is permitted.
  14. The patient has an active infection and/or is receiving antibiotics. The patient has received i.v. administration of antibiotics within two weeks prior to first study treatment or oral antibiotics within one week prior to first study treatment.
  15. 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: NCT01513109

Locations
Belgium
Institut Jules Bordet, tumor center of the Universite Libre de Bruxelles Recruiting
Brussels, Belgium, 1000
Contact: Catherine Primo, Mrs    +32 2 541 37 16    catherine.primo@bordet.be   
Contact: Redouane Rouas, Mr    +32 2 541 37 27    mrouas@ulb.ac.be   
Principal Investigator: Philippe Martiat, MD PhD         
Sponsors and Collaborators
Jules Bordet Institute
Investigators
Principal Investigator: Philippe Martiat, MD PhD Institut Jules Bordet
  More Information

Publications:

Responsible Party: Jules Bordet Institute
ClinicalTrials.gov Identifier: NCT01513109     History of Changes
Other Study ID Numbers: BORLEUWT01
Study First Received: January 16, 2012
Last Updated: January 19, 2012
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by Jules Bordet Institute:
WT1 positive Acute Myeloid Leukemia
Antigen specific cancer immunotherapeutic
Ex vivo regulatory T cell depletion
In vivo regulatory T cell depletion

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

ClinicalTrials.gov processed this record on October 22, 2014