Efficacy of Dendritic Cell Therapy for Myeloid Leukemia and Myeloma

NCT00965224 | Completed Phase 2

• 1 other identifier: CCRG 09-003
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

Dendritic cell therapy is a promising strategy for adjuvant cancer therapy in the setting of minimal residual disease (MRD) to fight off cancer relapse and/or progression. The investigators already performed a phase I safety study in leukemia patients that were in complete remission demonstrating the absence of side effects and feasibility of the therapy. Here, the investigators want to extend on this strategy by studying the clinical efficacy of autologous DC vaccination in patients with acute and chronic myeloid leukemia and myeloma patients. Effects of DC therapy on the immune reactivity towards leukemia cells as well as clinical parameters such molecular MRD monitoring, time to relapse (TTR), progression-free survival (PFS) and overall survival(OS) will be studied in vaccinated and non-vaccinated (control) patients. Patients will be vaccinated using their own dendritic cells electroporated with mRNA coding for the full-length Wilms' tumor antigen WT1.

Conditions

Acute Myeloid Leukemia; Chronic Myeloid Leukemia; Multiple Myeloma

Keywords

AML (acute myeloid leukemia); CML (chronic myeloid leukemia); MM (multiple myeloma)

Outcome Measures

Primary Outcomes (2)

• Immunogenicity of WT1 mRNA-transfected DC vaccination

  Upon completion of blood sample collection (before start of the vaccination at week 0 and 8 weeks after start of the vaccination) and skin biopsy collection (8 weeks after start of the vaccination) for all included patients

• Induction/maintenance of molecular remission as evidenced by molecular MRD monitoring of WT1 (AML, CML and MM) and BCR/ABL RNA (CML) copies in peripheral blood

  Upon follow-up completion for all included patients, i.e. until 24 months after the last vaccination

Secondary Outcomes (3)

• Time to relapse (TTR)

  Upon follow-up completion for all included patients, i.e. until 24 months after the last vaccination

• progression-free survival

  Upon follow-up completion for all included patients, i.e. until 24 months after the last vaccination

• overall survival (OS)

  Upon follow-up completion for all included patients, i.e. until 24 months after the last vaccination

Study Arms (1)

standard therapy + vaccination

EXPERIMENTAL

Biological: dendritic cell vaccination (active specific immunotherapy)

Interventions

dendritic cell vaccination (active specific immunotherapy) BIOLOGICAL

standard therapy + vaccination

Eligibility Criteria

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

You may qualify if:

• Acute Myeloid Leukemia (AML): all FAB subtypes except M3. Extent of disease:
• clinical remission after at least one course of polychemotherapy
• high risk of relapse due to age (\> 60 years) or poor risk cytogenetic/molecular markers or hyperleukocytosis at presentation or previous relapse
• Chronic myeloid leukemia (CML): patients in chronic phase under therapy with tyrosinase kinase inhibitors who have sub-optimal response or failure and who are not eligible for hematopoietic stem cell transplantation.
• Multiple Myeloma (MM): symptomatic with active disease, independent of earlier and/or concomitant treatment:
• Presence of serum/urine M protein (\> 3 g/dl)
• Bone marrow plasmacytosis (\>10-30%)
• Anemia, renal failure, hypercalcemia, and/or lytic bone lesions
• Overexpression of WT1 RNA in peripheral blood and or bone marrow as assessed by quantitative RT-PCR at the time of presentation.For CML: residual molecular disease as demonstrated by BCR-ABL RT-PCR
• Prior treatments: Patients must have received at least one prior antileukemic chemotherapeutic regimen and must be more than 1 month past the last treatment.
• Age: ≥ 18 years
• Performance status: WHO PS grade 0-1 (Appendix B)
• Objectively assessable parameters of life expectancy: more than 3 months
• Prior and concomitant associated diseases allowed with the exception of underlying autoimmune disease and positive serology for HIV/HBV/HCV
• No concomitant use of immunosuppressive drugs

You may not qualify if:

• Subjects with concurrent additional malignancy (with exception of non-melanoma skin cancers and carcinoma in situ of the cervix)
• Subjects who are pregnant
• Subjects who have sensitivity to drugs that provide local anesthesia
• Subjects needing corticosteroids 1 mg/kg during vaccination; corticosteroids are allowed as part of their treatment when taken ≥ 30 days before the start of vaccination.

Sponsors & Collaborators

• Zwi Berneman: lead

Study Sites (1)

University Hospital Antwerp

Edegem, Antwerp, 2650, Belgium

Location

Related Publications (5)

• 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

• Smits EL, Berneman ZN, Van Tendeloo VF. Immunotherapy of acute myeloid leukemia: current approaches. Oncologist. 2009 Mar;14(3):240-52. doi: 10.1634/theoncologist.2008-0165. Epub 2009 Mar 16.

  PMID: 19289488 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

• 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 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Multiple Myeloma

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor Dr. Zwi Berneman

Study Record Dates

• First Submitted: August 24, 2009
• First Posted: August 25, 2009
• Study Start: January 1, 2010
• Primary Completion: December 1, 2014
• Study Completion: March 7, 2019
• Last Updated: December 13, 2024

Record last verified: 2024-12

Locations

BE (1)