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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)

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified January 2012 by Jules Bordet Institute.
Recruitment status was:  Recruiting
ClinicalTrials.gov Identifier:
First Posted: January 20, 2012
Last Update Posted: January 20, 2012
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Jules Bordet Institute
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: Intervention Model: Single Group Assignment
Masking: None (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 ]

Secondary Outcome Measures:
  • Immunogenicity of the WT1 ASCI [ Time Frame: 4 years ]

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).

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01513109

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
Principal Investigator: Philippe Martiat, MD PhD Jules Bordet Institute
  More Information

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. Review.
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. Review.
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. Review.
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.
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.
Casalegno-Garduño 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. Review.
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, Håkansson 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. Review.
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. Review.
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. Review.
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.
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.
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.
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.
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. Review.
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.
Ghiringhelli F, Menard C, Puig PE, Ladoire S, Roux S, Martin F, Solary E, Le Cesne A, Zitvogel L, Chauffert B. Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother. 2007 May;56(5):641-8. Epub 2006 Sep 8.
Golovina TN, Vonderheide RH. Regulatory T cells: overcoming suppression of T-cell immunity. Cancer J. 2010 Jul-Aug;16(4):342-7. doi: 10.1097/PPO.0b013e3181eb336d. Review.
Ochsenreither S, Fusi A, Busse A, Bauer S, Scheibenbogen C, Stather D, Thiel E, Keilholz U, Letsch A. "Wilms Tumor Protein 1" (WT1) peptide vaccination-induced complete remission in a patient with acute myeloid leukemia is accompanied by the emergence of a predominant T-cell clone both in blood and bone marrow. J Immunother. 2011 Jan;34(1):85-91. doi: 10.1097/CJI.0b013e3181f3cc5c.
Keilholz U, Letsch A, Busse A, Asemissen AM, Bauer S, Blau IW, Hofmann WK, Uharek L, Thiel E, Scheibenbogen C. A clinical and immunologic phase 2 trial of Wilms tumor gene product 1 (WT1) peptide vaccination in patients with AML and MDS. Blood. 2009 Jun 25;113(26):6541-8. doi: 10.1182/blood-2009-02-202598. Epub 2009 Apr 23.
Maslak PG, Dao T, Krug LM, Chanel S, Korontsvit T, Zakhaleva V, Zhang R, Wolchok JD, Yuan J, Pinilla-Ibarz J, Berman E, Weiss M, Jurcic J, Frattini MG, Scheinberg DA. Vaccination with synthetic analog peptides derived from WT1 oncoprotein induces T-cell responses in patients with complete remission from acute myeloid leukemia. Blood. 2010 Jul 15;116(2):171-9. doi: 10.1182/blood-2009-10-250993. Epub 2010 Apr 16.
Mougiakakos D, Choudhury A, Lladser A, Kiessling R, Johansson CC. Regulatory T cells in cancer. Adv Cancer Res. 2010;107:57-117. doi: 10.1016/S0065-230X(10)07003-X. Review.
Nakahara T, Uchi H, Lesokhin AM, Avogadri F, Rizzuto GA, Hirschhorn-Cymerman D, Panageas KS, Merghoub T, Wolchok JD, Houghton AN. Cyclophosphamide enhances immunity by modulating the balance of dendritic cell subsets in lymphoid organs. Blood. 2010 Jun 3;115(22):4384-92. doi: 10.1182/blood-2009-11-251231. Epub 2010 Feb 12.
Nishikawa H, Sakaguchi S. Regulatory T cells in tumor immunity. Int J Cancer. 2010 Aug 15;127(4):759-67. doi: 10.1002/ijc.25429. Review.
Millar MR, MacKay P, Levene M, Langdale V, Martin C. Enterobacteriaceae and neonatal necrotising enterocolitis. Arch Dis Child. 1992 Jan;67(1 Spec No):53-6.
Oka Y, Sugiyama H. WT1 peptide vaccine, one of the most promising cancer vaccines: its present status and the future prospects. Immunotherapy. 2010 Sep;2(5):591-4. doi: 10.2217/imt.10.58.
Radojcic V, Bezak KB, Skarica M, Pletneva MA, Yoshimura K, Schulick RD, Luznik L. Cyclophosphamide resets dendritic cell homeostasis and enhances antitumor immunity through effects that extend beyond regulatory T cell elimination. Cancer Immunol Immunother. 2010 Jan;59(1):137-48. doi: 10.1007/s00262-009-0734-3. Epub 2009 Jul 10.
Rezvani K. Peptide vaccine therapy for leukemia. Int J Hematol. 2011 Mar;93(3):274-80. doi: 10.1007/s12185-011-0781-3. Epub 2011 Mar 8. Review.
Sakaguchi S. Regulatory T cells: history and perspective. Methods Mol Biol. 2011;707:3-17. doi: 10.1007/978-1-61737-979-6_1. Review.
Schabowsky RH, Madireddi S, Sharma R, Yolcu ES, Shirwan H. Targeting CD4+CD25+FoxP3+ regulatory T-cells for the augmentation of cancer immunotherapy. Curr Opin Investig Drugs. 2007 Dec;8(12):1002-8. Review.
Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science. 2011 Mar 25;331(6024):1565-70. doi: 10.1126/science.1203486. Review.
Sistigu A, Viaud S, Chaput N, Bracci L, Proietti E, Zitvogel L. Immunomodulatory effects of cyclophosphamide and implementations for vaccine design. Semin Immunopathol. 2011 Jul;33(4):369-83. doi: 10.1007/s00281-011-0245-0. Epub 2011 May 25. Review.
Van Tendeloo VF, Van de Velde A, Van Driessche A, Cools N, Anguille S, Ladell K, Gostick E, Vermeulen K, Pieters K, Nijs G, Stein B, Smits EL, Schroyens WA, Gadisseur AP, Vrelust I, Jorens PG, Goossens H, de Vries IJ, Price DA, Oji Y, Oka Y, Sugiyama H, Berneman ZN. Induction of complete and molecular remissions in acute myeloid leukemia by Wilms' tumor 1 antigen-targeted dendritic cell vaccination. Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13824-9. doi: 10.1073/pnas.1008051107. Epub 2010 Jul 14.
Wang X, Zheng J, Liu J, Yao J, He Y, Li X, Yu J, Yang J, Liu Z, Huang S. Increased population of CD4(+)CD25(high), regulatory T cells with their higher apoptotic and proliferating status in peripheral blood of acute myeloid leukemia patients. Eur J Haematol. 2005 Dec;75(6):468-76.
Wrzesinski C, Paulos CM, Kaiser A, Muranski P, Palmer DC, Gattinoni L, Yu Z, Rosenberg SA, Restifo NP. Increased intensity lymphodepletion enhances tumor treatment efficacy of adoptively transferred tumor-specific T cells. J Immunother. 2010 Jan;33(1):1-7. doi: 10.1097/CJI.0b013e3181b88ffc.

Responsible Party: Jules Bordet Institute
ClinicalTrials.gov Identifier: NCT01513109     History of Changes
Other Study ID Numbers: BORLEUWT01
First Submitted: January 16, 2012
First Posted: January 20, 2012
Last Update Posted: January 20, 2012
Last Verified: January 2012

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, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type

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