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DC Vaccination in CML

Primary Purpose

Myeloid Leukemia, Chronic

Status

Terminated

Phase

Phase 1

Locations

Germany

Study Type

Interventional

Intervention

DC vaccine

About this trial

This is an interventional treatment trial for Myeloid Leukemia, Chronic focused on measuring CML, DC vaccine

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.
Treatment with a TKI inhibitor and an additional anti leukemic drug is no exclusion criterion.
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

Exclusion Criteria:

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
Subjects for whom there is concern about compliance with the protocol procedures
Present History of substance abuse (drug or alcohol) or any other factor (e.g., serious psychiatric condition) that could limit the subject's ability to comply with study procedures

Sites / Locations

Charité - University Medicine Berlin
Klinikum Bremen Mitte

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

DC vaccine

Arm Description

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)

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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

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

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

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

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

Full Information

NCT ID

NCT02543749

First Posted

August 25, 2015

Last Updated

February 7, 2023

Sponsor

Charite University, Berlin, Germany

1. Study Identification

Unique Protocol Identification Number

NCT02543749

Brief Title

DC Vaccination in CML

Official Title

Dendritic Cells as Autologous Vaccine in Patients With Chronic Myeloid Leukemia

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Terminated

Study Start Date

July 2014 (undefined)

Primary Completion Date

July 2022 (Actual)

Study Completion Date

July 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Charite University, Berlin, Germany

4. Oversight

Data Monitoring Committee

5. Study Description

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: not achieved a CMR (complete molecular response) or achieved bcr/abl < 10% on qPCR (quantitative polymerase chain reaction) (=MCyR) (Major cytogenic Response), but less than a CCyR (complete cytogenic Response). Autologous DC (Dendritic cells), generated under GMP (Good manufacturing conditions) conditions, are used as a vaccine. These DC constitutively express all putative tumor antigens. In order to ensure sufficient presentation of distinct CML-related antigens, particularly in good responders to TKIs, DC are additionally pulsed with peptides from bcr/abl, WT-1 (Wilms Tumor Protein) and proteinase-3. Monitoring of T cell reactivity against these peptides can then serve as surrogate marker for anti leukemic immunity induced by the vaccine. Vaccination is performed with 10^7 DC i.d. (intra dermal) in weeks 1, 3, 5, 8, 11, 14, 17, 20, 23 and 26. KLH (keyhole limpet hemocyanin) is used as an adjuvant for vaccine preparations in weeks 3, 5 and 8 (and 11).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Myeloid Leukemia, Chronic

Keywords

CML, DC vaccine

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Arm Title

DC vaccine

Arm Type

Experimental

Arm Description

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)

Intervention Type

Biological

Intervention Name(s)

DC vaccine

Intervention Description

Autologous DC pulsed with leukemia-associated peptides+adjuvant

Primary Outcome Measure Information:

Title

DC toxicity Parameters using CTC (Common toxicity criteria)

Description

Time Frame

30 weeks

Secondary Outcome Measure Information:

Title

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

Time Frame

30 weeks

Title

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

Time Frame

30 weeks

Title

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

Time Frame

30 weeks

Title

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

Time Frame

30 weeks

Title

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

Time Frame

30 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Treatment with a TKI inhibitor and an additional anti leukemic drug is no exclusion criterion. 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 Exclusion Criteria: 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 Subjects for whom there is concern about compliance with the protocol procedures Present History of substance abuse (drug or alcohol) or any other factor (e.g., serious psychiatric condition) that could limit the subject's ability to comply with study procedures

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

J. Westermann, Prof. Dr.

Organizational Affiliation

Charite University, Berlin, Germany

Official's Role

Principal Investigator

Facility Information:

Facility Name

Charité - University Medicine Berlin

City

Berlin

ZIP/Postal Code

13353

Country

Germany

Facility Name

Klinikum Bremen Mitte

City

Bremen

ZIP/Postal Code

28177

Country

Germany

12. IPD Sharing Statement

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DC Vaccination in CML

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