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Acute Myelogenous LeukemiaPhase 1/2ASCINCT01513109

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

A Phase 1/2 study testing Recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) in people with Acute Myelogenous Leukemia and Myeloid Leukemia in Remission, run by Jules Bordet Institute at 1 site in Belgium.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteBelgium
Study dates
Dec 2011to Dec 2014
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The patient has cytologically proven AML, as defined by the WHO classification. The leukemia is a de novo or a secondary leukemia.
  • 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.
  • 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)
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  • 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.
  • The patient's blasts cells show over-expression of WT1 transcripts, detected in peripheral blood by qRT-PCR at diagnosis or at first relapse.
  • 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 signing of the ICF.
  • ECOG performance status of 0, 1, or 2 at the time of enrollment.
  • 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.
  • 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.
  • Under the investigator criteria, the patient is able to comply with the protocol requirements during the duration of the study.
  • 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.

Who cannot join

  • 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
  • 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 .
  • 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 received, is receiving (or is due to receive) allo-HSCT.
  • The patient has (or has had) concomitant malignancies, except effectively treated malignancy that is considered by the investigator highly likely to have been cured.
  • The patient is known to be human immunodeficiency virus (HIV)-positive.
Show all 15Show fewer
  • The patient has symptomatic autoimmune disease such as, but not limited to, multiple sclerosis, lupus, rheumatoid arthritis and inflammatory bowel disease.
  • 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 congestive heart failure, symptomatic 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 medication within 30 days preceding the first dose of study medication, or plans to receive such a drug during the study period.
  • 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.
  • 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.
  • For female patients: the patient is pregnant or lactating.

Trial locations and contacts

1 site in 1 country.

Belgium1 site, 1 recruiting

  • Institut Jules Bordet, tumor center of the Universite Libre de Bruxelles

    Brussels, 1000

    Catherine Primo, Mrs, +32 2 541 37 16, catherine.primo@bordet.be

    Redouane Rouas, Mr, +32 2 541 37 27, mrouas@ulb.ac.be

    Recruiting

Other trials in Belgium

About this study

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).

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

Read the 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).

Being tested
Recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI)
Keywords
WT1 positive Acute Myeloid Leukemia, Antigen specific cancer immunotherapeutic, Ex vivo regulatory T cell depletion, In vivo regulatory T cell depletion
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI)Biological

    i.m. administration

Study groups in NCT01513109
Study groupRoleWhat they receive
Treatment armExperimentalRecombinant WT1 Antigen-Specific Cancer Immunotherapeutic combined with Treg depletion
Receives: Biological: Recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Occurence of severe toxicities

    Measured: 4 years

Secondary outcomes (1)

  1. Immunogenicity of the WT1 ASCI

    Measured: 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jan 2012 (estimated)
  2. Study startDec 2011
  3. Primary completionDec 2013 (estimated)
  4. Study completionDec 2014 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01513109
Sponsor's protocol ID
BORLEUWT01
Acronym
ASCI
Status last verified
Jan 2012
First submitted
16 Jan 2012
Last updated
20 Jan 2012
Results posted
No
Data monitoring committee
No

Publications

  • Alatrash G, Molldrem JJ. Vaccines as consolidation therapy for myeloid leukemia. Expert Rev Hematol. 2011 Feb;4(1):37-50. doi: 10.1586/ehm.10.80.

    PubMed 21322777

  • Barrett AJ, Le Blanc K. Immunotherapy prospects for acute myeloid leukaemia. Clin Exp Immunol. 2010 Aug;161(2):223-32. doi: 10.1111/j.1365-2249.2010.04197.x. Epub 2010 May 31.

    PubMed 20529084

  • Cao X. Regulatory T cells and immune tolerance to tumors. Immunol Res. 2010 Mar;46(1-3):79-93. doi: 10.1007/s12026-009-8124-7.

    PubMed 19763889

  • Zhao J, Cao Y, Lei Z, Yang Z, Zhang B, Huang B. Selective depletion of CD4+CD25+Foxp3+ regulatory T cells by low-dose cyclophosphamide is explained by reduced intracellular ATP levels. Cancer Res. 2010 Jun 15;70(12):4850-8. doi: 10.1158/0008-5472.CAN-10-0283. Epub 2010 May 25.

    PubMed 20501849

  • Cao Y, Zhao J, Yang Z, Cai Z, Zhang B, Zhou Y, Shen GX, Chen X, Li S, Huang B. CD4+FOXP3+ regulatory T cell depletion by low-dose cyclophosphamide prevents recurrence in patients with large condylomata acuminata after laser therapy. Clin Immunol. 2010 Jul;136(1):21-9. doi: 10.1016/j.clim.2010.02.020. Epub 2010 Mar 24.

    PubMed 20338811

  • Casalegno-Garduno R, Schmitt A, Wang X, Xu X, Schmitt M. Wilms' tumor 1 as a novel target for immunotherapy of leukemia. Transplant Proc. 2010 Oct;42(8):3309-11. doi: 10.1016/j.transproceed.2010.07.034.

    PubMed 20970678

  • Copier J, Dalgleish AG, Britten CM, Finke LH, Gaudernack G, Gnjatic S, Kallen K, Kiessling R, Schuessler-Lenz M, Singh H, Talmadge J, Zwierzina H, Hakansson L. Improving the efficacy of cancer immunotherapy. Eur J Cancer. 2009 May;45(8):1424-31. doi: 10.1016/j.ejca.2008.12.017. Epub 2009 Jan 21.

    PubMed 19167214

  • Nizar S, Copier J, Meyer B, Bodman-Smith M, Galustian C, Kumar D, Dalgleish A. T-regulatory cell modulation: the future of cancer immunotherapy? Br J Cancer. 2009 Jun 2;100(11):1697-703. doi: 10.1038/sj.bjc.6605040. Epub 2009 Apr 21.

    PubMed 19384299

  • Dao T, Scheinberg DA. Peptide vaccines for myeloid leukaemias. Best Pract Res Clin Haematol. 2008 Sep;21(3):391-404. doi: 10.1016/j.beha.2008.05.001.

    PubMed 18790445

  • Tsuboi A, Oka Y, Kyo T, Katayama Y, Elisseeva OA, Kawakami M, Nishida S, Morimoto S, Murao A, Nakajima H, Hosen N, Oji Y, Sugiyama H. Long-term WT1 peptide vaccination for patients with acute myeloid leukemia with minimal residual disease. Leukemia. 2012 Jun;26(6):1410-3. doi: 10.1038/leu.2011.343. Epub 2011 Dec 13. No abstract available.

    PubMed 22157809

  • Tamura H, Dan K, Yokose N, Iwakiri R, Ohta M, Sakamaki H, Tohyama K, Kondo A, Hyodo H, Nakamura K, Yamashita T, Elisseeva OA, Oka Y, Oji Y, Sugiyama H, Ogata K. Prognostic significance of WT1 mRNA and anti-WT1 antibody levels in peripheral blood in patients with myelodysplastic syndromes. Leuk Res. 2010 Aug;34(8):986-90. doi: 10.1016/j.leukres.2009.11.029. Epub 2010 Jan 19.

    PubMed 20031209

  • Fujiki F, Oka Y, Kawakatsu M, Tsuboi A, Nakajima H, Elisseeva OA, Harada Y, Li Z, Tatsumi N, Kamino E, Shirakata T, Nishida S, Taniguchi Y, Kawase I, Oji Y, Sugiyama H. A WT1 protein-derived, naturally processed 16-mer peptide, WT1(332), is a promiscuous helper peptide for induction of WT1-specific Th1-type CD4(+) T cells. Microbiol Immunol. 2008 Dec;52(12):591-600. doi: 10.1111/j.1348-0421.2008.00080.x.

    PubMed 19120973

  • Elisseeva OA, Oka Y, Tsuboi A, Ogata K, Wu F, Kim EH, Soma T, Tamaki H, Kawakami M, Oji Y, Hosen N, Kubota T, Nakagawa M, Yamagami T, Hiraoka A, Tsukaguchi M, Udaka K, Ogawa H, Kishimoto T, Nomura T, Sugiyama H. Humoral immune responses against Wilms tumor gene WT1 product in patients with hematopoietic malignancies. Blood. 2002 May 1;99(9):3272-9. doi: 10.1182/blood.v99.9.3272.

    PubMed 11964293

  • Elkord E, Alcantar-Orozco EM, Dovedi SJ, Tran DQ, Hawkins RE, Gilham DE. T regulatory cells in cancer: recent advances and therapeutic potential. Expert Opin Biol Ther. 2010 Nov;10(11):1573-86. doi: 10.1517/14712598.2010.529126.

    PubMed 20955112

  • Fujiki F, Oka Y, Kawakatsu M, Tsuboi A, Tanaka-Harada Y, Hosen N, Nishida S, Shirakata T, Nakajima H, Tatsumi N, Hashimoto N, Taguchi T, Ueda S, Nonomura N, Takeda Y, Ito T, Myoui A, Izumoto S, Maruno M, Yoshimine T, Noguchi S, Okuyama A, Kawase I, Oji Y, Sugiyama H. A clear correlation between WT1-specific Th response and clinical response in WT1 CTL epitope vaccination. Anticancer Res. 2010 Jun;30(6):2247-54.

    PubMed 20651376

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Recombinant WT1 Antigen-Specific Cancer Immunotherapeutic (ASCI) in people with Acute Myelogenous Leukemia and Myeloid Leukemia in Remission, run by Jules Bordet Institute at 1 site in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 20 Jan 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Occurence of severe toxicities (time frame: 4 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01513109, which also lists 34 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2012.

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