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Trial Title:
Safety and Immunogenicity of Recombinant WT1 Antigen-Specific Cancer Immunotherapeutic Combined With Infusion of Treg Depleted T Cells for Adult WT1 Acute Myeloid Leukemia
NCT ID:
NCT01513109
Condition:
Acute Myelogenous Leukemia
Myeloid Leukemia in Remission
Effects of Immunotherapy
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Conditions: Keywords:
WT1 positive Acute Myeloid Leukemia
Antigen specific cancer immunotherapeutic
Ex vivo regulatory T cell depletion
In vivo regulatory T cell depletion
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Unknown status
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI)
Description:
i.m. administration
Arm group label:
Treatment arm
Summary:
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
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).
Criteria for eligibility:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Institut Jules Bordet, tumor center of the Universite Libre de Bruxelles
Address:
City:
Brussels
Zip:
1000
Country:
Belgium
Status:
Recruiting
Contact:
Last name:
Catherine Primo, Mrs
Phone:
+32 2 541 37 16
Email:
catherine.primo@bordet.be
Contact backup:
Last name:
Redouane Rouas, Mr
Phone:
+32 2 541 37 27
Email:
mrouas@ulb.ac.be
Investigator:
Last name:
Philippe Martiat, MD PhD
Email:
Principal Investigator
Start date:
December 2011
Completion date:
December 2014
Lead sponsor:
Agency:
Jules Bordet Institute
Agency class:
Other
Source:
Jules Bordet Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT01513109