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Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Wilms Tumor

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Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

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Acute Graft Versus Host Disease

Wilms' Tumor

All Drugs and Chemicals

Vaccines

intradermal injection of WT1-RNA-electroporated autologous dendritic cell vaccine (therapeutic cell vaccine)

injection of antigen-loaded cultured dendritic cells

Zwi Berneman, MD, PHD

Ann Van de Velde, MD

Viggo FI Van Tendeloo, PhD

RATIONALE: Vaccines made from a patient's white blood cells (dendritic cells) and a specific leukemia antigen (Wilms tumor antigen-1) may induce an effective immune response to kill residual leukemic cells and/or prevent leukemia relapse.

PURPOSE: This phase I/II trial is studying the feasibility, safety and efficacy of intradermal mRNA-transfected dendritic cell vaccination therapy in patients with acute myeloid leukemia.

Autologous dendritic cell (DC) vaccination is a promising strategy for adjuvant cancer therapy in the setting of minimal residual disease (MRD). We performed a phase I/II trial in patients with acute myeloid leukemia (AML) where patients received intradermal injections of autologous DC loaded with mRNA coding for the Wilms' tumor protein (WT1). WT1 is highly overexpressed in leukemia and the level of WT1 RNA in peripheral blood is a useful biomarker for molecular diagnosis en follow-up in the MRD setting. We want to prospectively monitor WT1 RNA expression in the peripheral blood of vaccinated and non-vaccinated AML patients in order to evaluate its predictive value as a biomarker for relapse and to assess the clinical efficacy of DC vaccination in acute myeloid leukemia patients. We believe, on the basis of already available evidence, that the use of WT1 both as a target for immunotherapy as well as a biomarker not holds promise to assess the efficacy of new experimental therapeutic interventions such as DC vaccination.

Dendritic Cell Vaccination for Patients With Acute Myeloid Leukemia in Remission

Wilms Tumor Gene (WT1) mRNA-transfected Autologous Dendritic Cell Vaccination for Patients With Acute Myeloid Leukemia (AML): a Phase I Trial

University Hospital, Antwerp

Prof dr Zwi Berneman

Immunomodulating Agents

Alloreactive NK cell infusion

Antonio Curti

Acute Myeloid Leukemia (AML) patients who had achieved Complete Remission (CR) after (re)induction/consolidation chemotherapy will receive the infusion of alloreactive NK cells. Adult AML patients in morphologic, but not cytogenetic and/or molecular CR and AML patients in morphologic plus cytogenetic and/or molecular CR, not eligible for Stem Cell Transplantation (SCT), will be included. Using a genetic randomization through a 'donor' vs 'no donor' approach, patients will undergo NK cell infusion (ARM 1) or followed-up without treatment (ARM 2). Donor alloreactive NK cell repertoire will be evaluated in order to determine the functional cell dose to be used for NK cell collection. NK cells will be selected from a steady-state large volume leukapheresis product from a suitable KIR-ligand incompatible donor. NK cell purification will be performed if the donor leukapheresis product contains at least 10x106 NK cells/Kg, otherwise the final decision for proceeding to NK purification will be made by the PI after careful evaluation of the number of alloreactive If the minimum collected cell dose of 2x105 total alloreactive NK cells/kg is not reached after a single leukapheresis, donors could undergo a second PB collection within 30 days from the first one. Patients will receive immunosuppressive chemotherapy, fludarabine (Flu) 25 mg/mq/ from day -7 to -3 and cyclophosphamide (Cy) 4 g/mq on day -2 (Flu/Cy). Immunosuppressive chemotherapy is not part of the procedures under study and it is used to favor NK cell engraftment. Two days after Cy administration, patients will be infused intravenously with a single dose of cryopreserved NK cells (day 0), which will be followed by subcutaneous administration of Interleuki (IL)-2 (10 x 106 IU/day, 3 times weekly) for 2 weeks (6 doses total). IL-2 administration is not part of the procedures under study and it is used to favor early in vivo expansion of infused NK cells. Peripheral blood samples will be collected for molecular assessment of microchimerism and tracking of NK cells for 30 days, immunophenotype studies, alloreactive NK cells cloning and functional assays. Bone marrow aspirate will be performed once a week until hematological recovery. Enrolled patients (ARM1 and 2) will be followed up for at least 12 months after NK cell infusion. RFS is defined as the time from patient enrollment to disease relapse.

INFUSION OF ALLOREACTIVE NATURAL KILLER (NK) CELLS AS CONSOLIDATION STRATEGY FOR ACUTE MYELOID LEUKEMIA PATIENTS

INFUSION OF ALLOREACTIVE NK CELLS AS CONSOLIDATION STRATEGY FOR ADULT ACUTE MYELOID LEUKEMIA PATIENTS: A MULTICENTER CLINICAL STUDY

relapse-free survival (RFS) of AML patients, not eligible for SCT, who undergo alloreactive NK cell infusion after the achievement of CR with induction/consolidation chemotherapy.

overall survival (RFS) of AML patients, not eligible for SCT, who undergo alloreactive NK cell infusion after the achievement of CR with induction/consolidation chemotherapy.

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Medical Doctor, Hematologist

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Dendritic Cell Vaccination for Patients With Acute Myeloid Leukemia in Remission	NCT00834002	Acute Myeloid L...	injection of an...	18 Years -	University Hospital, Antwerp
INFUSION OF ALLOREACTIVE NATURAL KILLER (NK) CELLS AS CONSOLIDATION STRATEGY FOR ACUTE MYELOID LEUKEMIA PATIENTS	NCT03955848	Adult Acute Mye...	Alloreactive NK...	-	IRCCS Azienda Ospedaliero-Universitaria di Bologna

Spots Global Cancer Trial Database for aml in remission