Efficacy Study of Dendritic Cell Vaccination in Patients With Acute Myeloid Leukemia in Remission

NCT01686334 | Active Not Recruiting Phase 2

• 1 other identifier: CCRG12-001
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 8

Brief Summary

The primary aim of this innovative immunotherapeutic study is to determine whether the antileukemic effects seen in our previous phase I/II study can be confirmed in a large cohort of patients and whether dendritic cell vaccination can significantly prevent relapse and increase survival of acute myeloid leukemia (AML) patients by eradicating minimal residual disease.

Conditions

Acute Myeloid Leukemia

Keywords

in complete remission; Adult (>18 years) at very high risk of relapse

Outcome Measures

Primary Outcomes (1)

• Overall survival

  The primary objective of this randomized phase II clinical study is to determine the effect of WT1-targeted dendritic cell vaccination on overall survival in adult AML patients at very high risk of relapse and in complete remission.

  At study completion, an average of 5 year

Secondary Outcomes (5)

• Relapse rate

  At study completion, an average of 5 year

• relapse-free survival

  At study completion, an average of 5 year

• Change in WT1 mRNA levels in peripheral blood

  Through study completion, at every vaccination during 2 years

• Immune activation

  After the 4th DC vaccine

• General and disease-specific quality of life

  At study completion, an average of 5 year

Other Outcomes (2)

• Tertiary: Safety

  At study completion, an average of 5 year

• Exploratory: Effect of low-intensity chemotherapy

  At study completion, an average of 5 year

Study Arms (2)

DC vaccine

EXPERIMENTAL

Vaccination with autologous WT1 mRNA-electroporated DCs plus follow-up care. Patients receiving low-intensity chemotherapy are allowed to continue this treatment in combination with DC vaccination.

Biological: DC vaccine

Control arm

NO INTERVENTION

Follow-up care. Patients receiving low-intensity chemotherapy are allowed to continue this treatment during the follow-up care

Interventions

DC vaccine BIOLOGICAL

Autologous WT1 mRNA-electroporated DCs

DC vaccine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of acute myeloid leukemia (AML) according to the 2008 criteria of the World Health Organization (WHO).
• all French-American-British (FAB) subtypes, except:
• \- M3 (acute promyelocytic leukemia)
• all cases of de novo AML or secondary AML with ≥ 20 % blasts in peripheral blood and/or bone marrow, except:
• AML secondary to myeloproliferative neoplasms (MPN)
• AML secondary to exposure of leukemogenic agents (t-AML) unless treated with CPX-351 chemotherapy or hypomethylating agents combined with venetoclax.
• Completion of one of the following treatment options:
• I) Intensive chemotherapy:
• (1) at least one cycle of induction chemotherapy and one cycle of consolidation chemotherapy (low-dose cytarabine as consolidation therapy is allowed) OR
• (2) one to two cycles of CPX-351 induction treatment and up to two cycles of CPX-351 consolidation treatment OR
• II) Low-intensity chemotherapy:
• (3) at least two cycles to maximum six cycles of hypomethylating agents whether or not combined with venetoclax OR
• (4) at least two cycles to maximum six cycles of low-dose cytarabine combined with venetoclax;
• resulting in:
• morphological complete remission (CR), i.e. bone marrow blast count \<5% with neutrophil count \>1000 cells/µL and platelet count \>100,000 cells/µL OR

You may not qualify if:

• Participation in any other interventional clinical trial during the study period.
• History or concomitant presence of any other malignancy, except for:
• non-melanoma skin cancer
• carcinoma in situ of the cervix
• any other effectively treated malignancy that has been in remission for \>5 years or that is highly likely to be cured at the time of enrollment.
• Concomitant presence of any immunosuppressive disease (e.g. HIV) or any active autoimmune condition, except for vitiligo.
• Concomitant use of systemic corticosteroids in immunosuppressive doses (\>1 mg/kg/day of prednisone, or equivalent dose for other corticosteroid preparations) or any other immunosuppressive agent. A minimum of 4 weeks must have elapsed between the last dose of immunosuppressive therapy and the first vaccination. Topical corticosteroids are permitted, except if applied at the sites of DC injection.
• Pregnant or breast-feeding

Sponsors & Collaborators

• Zwi Berneman: lead
• Kom Op Tegen Kanker: collaborator
• Stichting tegen Kanker: collaborator
• Research Foundation Flanders: collaborator

Study Sites (8)

ZNA Cadix

Antwerp, 2030, Belgium

Location

Antwerp University Hospital

Antwerp, 2650, Belgium

Location

University Hospital Brussels

Brussels, 1090, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Ghent University Hospital

Ghent, 9000, Belgium

Location

Centre Hospitalier Universitaire de Liège

Liège, 4000, Belgium

Location

AZ Delta

Roeselare, 8800, Belgium

Location

CHU Mont Godinne

Yvoir, 5530, Belgium

Location

Related Publications (13)

• 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.

  PMID: 20631300 BACKGROUND

• Van Driessche A, Van de Velde AL, Nijs G, Braeckman T, Stein B, De Vries JM, Berneman ZN, Van Tendeloo VF. Clinical-grade manufacturing of autologous mature mRNA-electroporated dendritic cells and safety testing in acute myeloid leukemia patients in a phase I dose-escalation clinical trial. Cytotherapy. 2009;11(5):653-68. doi: 10.1080/14653240902960411.

  PMID: 19530029 BACKGROUND

• Van Driessche A, Gao L, Stauss HJ, Ponsaerts P, Van Bockstaele DR, Berneman ZN, Van Tendeloo VF. Antigen-specific cellular immunotherapy of leukemia. Leukemia. 2005 Nov;19(11):1863-71. doi: 10.1038/sj.leu.2403930.

  PMID: 16121214 BACKGROUND

• Van Driessche A, Berneman ZN, Van Tendeloo VF. Active specific immunotherapy targeting the Wilms' tumor protein 1 (WT1) for patients with hematological malignancies and solid tumors: lessons from early clinical trials. Oncologist. 2012;17(2):250-9. doi: 10.1634/theoncologist.2011-0240. Epub 2012 Jan 30.

  PMID: 22291091 BACKGROUND

• Anguille S, Willemen Y, Lion E, Smits EL, Berneman ZN. Dendritic cell vaccination in acute myeloid leukemia. Cytotherapy. 2012 Jul;14(6):647-56. doi: 10.3109/14653249.2012.693744.

  PMID: 22686130 BACKGROUND

• Anguille S, Lion E, Smits E, Berneman ZN, van Tendeloo VF. Dendritic cell vaccine therapy for acute myeloid leukemia: questions and answers. Hum Vaccin. 2011 May;7(5):579-84. doi: 10.4161/hv.7.5.14652. Epub 2011 May 1.

  PMID: 21422813 BACKGROUND

• Smits EL, Anguille S, Cools N, Berneman ZN, Van Tendeloo VF. Dendritic cell-based cancer gene therapy. Hum Gene Ther. 2009 Oct;20(10):1106-18. doi: 10.1089/hum.2009.145.

  PMID: 19656053 BACKGROUND

• Anguille S, Van de Velde AL, Smits EL, Van Tendeloo VF, Juliusson G, Cools N, Nijs G, Stein B, Lion E, Van Driessche A, Vandenbosch I, Verlinden A, Gadisseur AP, Schroyens WA, Muylle L, Vermeulen K, Maes MB, Deiteren K, Malfait R, Gostick E, Lammens M, Couttenye MM, Jorens P, Goossens H, Price DA, Ladell K, Oka Y, Fujiki F, Oji Y, Sugiyama H, Berneman ZN. Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia. Blood. 2017 Oct 12;130(15):1713-1721. doi: 10.1182/blood-2017-04-780155. Epub 2017 Aug 22.

  PMID: 28830889 BACKGROUND

• Van Acker HH, Versteven M, Lichtenegger FS, Roex G, Campillo-Davo D, Lion E, Subklewe M, Van Tendeloo VF, Berneman ZN, Anguille S. Dendritic Cell-Based Immunotherapy of Acute Myeloid Leukemia. J Clin Med. 2019 Apr 27;8(5):579. doi: 10.3390/jcm8050579.

  PMID: 31035598 BACKGROUND

• Smits EL, Stein B, Nijs G, Lion E, Van Tendeloo VF, Willemen Y, Anguille S, Berneman ZN. Generation and Cryopreservation of Clinical Grade Wilms' Tumor 1 mRNA-Loaded Dendritic Cell Vaccines for Cancer Immunotherapy. Methods Mol Biol. 2016;1393:27-35. doi: 10.1007/978-1-4939-3338-9_3.

  PMID: 27033213 BACKGROUND

• Z. Berneman, S. Anguille, Y. Willemen, A. Van de Velde, P. Germonpré, M. Huizing, V. Van Tendeloo, K. Saevels, L. Rutsaert, K. Vermeulen, A. Snoeckx, B. Op de Beeck, N. Cools, G. Nijs, B. Stein, E. Lion, A. van Driessche, M. Peeters, E. Smits. Vaccination of cancer patients with dendritic cells electroporated with mRNA encoding the Wilms' Tumor protein (WT1): correlation of clinical effect and overall survival with T-cell response. Cytotherapy 2019, 21(5), p. S10.

  BACKGROUND

• Z. Berneman, A. Van de Velde, S. Anguille, Y. Willemen, M. Huizing, P. Germonpré, K. Saevels, G. Nijs, N. Cools, A. Van Driessche, B. Stein, H. De Reu, W. Schroyens, A. Gadisseur, A. Verlinden, K. Vermeulen, M. Maes, M. Lammens, H. Goossens, M. Peeters, V. Van Tendeloo, E. Smits. Vaccination with Wilms' Tumor Antigen (WT1) mRNA-Electroporated Dendritic Cells as an Adjuvant Treatment in 60 Cancer Patients: Report of Clinical Effects and Increased Survival in Acute Myeloid Leukemia, Metastatic Breast Cancer, Glioblastoma and Mesothelioma. Cytotherapy 2016, 18(6), p. S13-14

  BACKGROUND

• Shallis RM, Podoltsev NA. Maintenance therapy for acute myeloid leukemia: sustaining the pursuit for sustained remission. Curr Opin Hematol. 2021 Mar 1;28(2):110-121. doi: 10.1097/MOH.0000000000000637.

  PMID: 33394722 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Pathologic Complete Response

Interventions

lentiviral minigene vaccine of COVID-19 coronavirus

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Progression; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Zwi Berneman, MD, PhD

  University Hospital, Antwerp

  STUDY DIRECTOR

• Evelien LJ Smits, MSc, PhD

  Universiteit Antwerpen

  PRINCIPAL INVESTIGATOR

• Sébastien Anguille, MD, PhD

  University Hospital, Antwerp

  PRINCIPAL INVESTIGATOR

• Ann Van de Velde, MD, PhD

  University Hospital, Antwerp

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Full Professor

Study Record Dates

• First Submitted: July 26, 2012
• First Posted: September 18, 2012
• Study Start: October 1, 2012
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 12, 2024

Record last verified: 2024-03

Locations

BE (8)