DC Vaccination in CML

NCT02543749 | Terminated Phase 1

• 2 other identifiers: CSTI571ADE602006-006962-41
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 2

Brief Summary

The aim of this phase I/II trial is induction of anti leukemic T cell immunity in a clinical situation of "minimal residual disease". This might be a strategy to immunologically eradicate the residual leukemia cells. Patients to be included are chronic phase bcr/abl+ CML (chronic myeloid leukemia) patients in stable cytogenetic and/or molecular remission. These patients can be included if they have:

1. 1.not achieved a CMR (complete molecular response) or
2. 2.achieved bcr/abl \< 10% on qPCR (quantitative polymerase chain reaction) (=MCyR) (Major cytogenic Response), but less than a CCyR (complete cytogenic Response).

Conditions

Myeloid Leukemia, Chronic

Keywords

CML; DC vaccine

Outcome Measures

Primary Outcomes (1)

• DC toxicity Parameters using CTC (Common toxicity criteria)

  Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 (Treatment: long-term vaccination with peptide-pulsed autologous DC in patients with chronic phase CML who have persistent residual cytogenetic and/or molecular disease after at least 18 months therapy with a tyrosine kinase Inhibitor)

  30 weeks

Secondary Outcomes (5)

• Molecular/cytogenetic Response under vaccination as measured by qPCR for bcr/abl in % IS (International scale)

  30 weeks

• T-cell Response: Antigen specific T-cell Response in % CD8+ T-cells for bcr/abl

  30 weeks

• T-cell Response: Antigen specific T-cell Response in % CD4+ T-cells for bcr/abl

  30 weeks

• T-cell Response: Antigen specific T-cell Response in % CD8+ T-cells for WT-1 (only in HLA-A2+ patients)

  30 weeks

• T-cell Response: Antigen specific T-cell Response in % CD8+ T-cells for Proteinase 3 (only in HLA-A2+ patients)

  30 weeks

Study Arms (1)

DC vaccine

EXPERIMENTAL

Autologous DC pulsed with leukemia-associated peptides+adjuvant. Ten vaccinations over 26 weeks with 10 x 106 freshly thawed DC Intradermal injections (1-2 ml volume)

Biological: DC vaccine

Interventions

DC vaccine BIOLOGICAL

Autologous DC pulsed with leukemia-associated peptides+adjuvant

DC vaccine

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with bcr/abl-positive CML in stable cytogenetic / molecular remission after at least 18 months therapy with tyrosine kinase Inhibitors (TKI). The following groups of patients will be included:
• complete cytogenetic remission (CCyR), but stable detection of bcr/abl-transcript on qPCR (at least on two different time points over a period of at least 6 months). A stable molecular remission is assumed, if the difference between the qPCR values does not exceed a factor 5 (\< 0,5log).
• No CCyR, but qPCR for bcr/abl transcript \< 10% (= MCyR (Major cytogenetic Response)) after at least 24 months on 2nd generation TKI therapy.
• Age 18-80 years
• Performance status of 0 or 1 according to WHO index or Karnofsky index \>70 %
• Life expectancy \> 18 months
• Hematological function should be at least partially conserved (platelets count \>50.000/ μl, Hb \> 8g/dl)
• written informed consent
• No breast feeding
• if of childbearing potential, negative pregnancy test (serum/urine ß- HCG ( human chorionic gonadotropin )) and willingness to use highly effective contraceptive methods (Pearl Index \<1, e.g.: birth control pill, loop, hormone implant, transdermal hormone patch, a combination of two barrier methods \[condom and vaginal diaphragm\] sterilisation or sexual abstinence) for the study duration and thereafter as long as under treatment with antileukemic drugs

You may not qualify if:

• Clinically relevant autoimmune disorders
• Immunodeficiency syndromes
• Known allergy to GM-CSF (granulocyte macrophage colony-stimulating factor), TNF-α (Tumor necrosis factor Alpha) , IL-4 (interleukine 4) or KLH (keyhole limpet hemocyanin)
• Pregnancy (absence confirmed by serum/urine ß-HCG) or breastfeeding
• Women of childbearing age without highly effective contraception
• Active infectious disease requiring treatment
• Continuous therapy with corticosteroids or other immunosuppressive drugs
• Severe psychiatric disorders
• Organ dysfunction:
• Thrombin Time / Partial Thromboplastin Time \> 1,5 x upper normal limit
• creatinine \> 2,0 mg/ml
• Bilirubin \> 3,0 mg/ml, ALAT/ASAT (Alanine aminotransferase/ aspartate aminotransferase) \> 3x upper normal limit
• pulmonary disfunction (dyspnea at rest or with minimal exertion)
• clinically relevant coronary heart disease or ventricular arrhythmia, congestive heart failure \> grade II NYHA (New York Heart Association)
• Persons who are detained officially or legally to an official institute

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead

Study Sites (2)

Charité - University Medicine Berlin

Berlin, 13353, Germany

Location

Klinikum Bremen Mitte

Bremen, 28177, Germany

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

lentiviral minigene vaccine of COVID-19 coronavirus

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• J. Westermann, Prof. Dr.

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Representative of the sponsor

Study Record Dates

• First Submitted: August 25, 2015
• First Posted: September 7, 2015
• Study Start: July 1, 2014
• Primary Completion: July 1, 2022
• Study Completion: July 1, 2022
• Last Updated: February 9, 2023

Record last verified: 2023-02

Locations

DE (2)