Efficacy of Dendritic Cell Therapy for Myeloid Leukemia and Myeloma

NCT ID: NCT00965224

Last Updated: 2024-12-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

38 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-01-31

Study Completion Date

2019-03-07

Brief Summary

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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.

Detailed Description

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Conditions

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Acute Myeloid Leukemia Chronic Myeloid Leukemia Multiple Myeloma

Keywords

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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standard therapy + vaccination

Group Type EXPERIMENTAL

dendritic cell vaccination (active specific immunotherapy)

Intervention Type BIOLOGICAL

Interventions

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dendritic cell vaccination (active specific immunotherapy)

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* 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
* adequate renal and liver function, i.e. creatinin and bilirubin = 1.2 times the upper limit of normal
* absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
* Women of child-bearing potential should use adequate contraception prior to study entry and for the duration of study participation

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Zwi Berneman

OTHER

Sponsor Role lead

Responsible Party

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Zwi Berneman

Professor Dr. Zwi Berneman

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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University Hospital Antwerp

Edegem, Antwerp, Belgium

Site Status

Countries

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Belgium

References

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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.

Reference Type BACKGROUND
PMID: 19530029 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19289488 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16121214 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19656053 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28830889 (View on PubMed)

Other Identifiers

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CCRG 09-003

Identifier Type: -

Identifier Source: org_study_id