iVAC-CLL01: Patient-individualized peptide vaccination after first line therapy of CLL

• Register: EUCTR
• Last refreshed on: 30 April 2019
• Main ID: EUCTR2015-005817-61-DE
• Date of registration: 13/04/2016
• Prospective Registration: Yes
• Primary sponsor: University Hospital Tuebingen
• Public title: iVAC-CLL01: Patient-individualized peptide vaccination after first line therapy of CLL
• Scientific title: iVAC-CLL01: Patient-individualized peptide vaccination after first line therapy of CLL - iVAC-CLL01
• Date of first enrolment: 28/07/2016
• Target sample size: 56
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-005817-61
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: yes; Other trial design description: Phase II multicentric open label interventional clinical trial, Patient stratification:MRD- and MRD+; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany

Contacts

• Name: Medical Department II
• Affiliation: University Hospital Tuebingen

• Name: Medical Department II
• Affiliation: University Hospital Tuebingen

Key inclusion & exclusion criteria

Inclusion criteria:
1. Documented diagnosis of CLL/SLL according to IWCLL
guidelines.
For Screening phase:
• No pretreatment of CLL/SLL
• Ability to mount an immune response: Positive
immunresponse to EBV/CMV peptide mix (analyzed
in 12 day recall IFN? ELISPOT).
For Vaccination phase:
• Achievement of response (at least PR according to
IWCLL guidelines) after first-line therapy according
to treating physicians choice.
2. HLA typing positive for HLA alleles of peptides included in
the warehouse with proven immunogenicity: HLA-A*01, A*02,
A*03, A*24, B*07, B*08.
3. Ability to understand and voluntarily sign an informed
consent form.
4. Age = 18 years at the time of signing the informed consent
form.
5. Ability to adhere to the study visit schedule and other
protocol requirements.
6. Eastern Cooperative Oncology Group (ECOG) performance
status score of = 2.
7. Negative serological Hepatitis B and C test or negative PCR
in case of positive serological test without evidence of an
active infection, negative HIV test within 6 weeks prior to
randomization.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 56
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. High risk CLL/SLL
• 17p-deletion or
• TP53 mutation
2. Pregnant or lactating females.
3. Participation in any clinical study or having taken any
investigational therapy, which would interfere with the studys
primary end point.
4. Patients who have received any other vaccine within 1
month prior to study inclusion.
5. Prior history of malignancies, other than CLL, unless the
subject has been free of the disease for = 5 years. Exceptions
include the following:
• Basal cell carcinoma of the skin
• Carcinoma in situ of the cervix
• Carcinoma in situ of the breast
• Incidental histological finding of prostate cancer (TNM
stage of T1a or T1b)
6. Any of the following laboratory abnormalities:
For Vaccination phase:
7. Disease transformation (active) (i.e. Richter’s Syndrome,
prolymphocytic leukemia).
8. Any immunosupressive treatment except corticosteroids.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) after first line therapy
MedDRA version: 20.0 Level: LLT Classification code 10009310 Term: CLL System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

Trade Name: Aldara 5% Creme
Pharmaceutical Form: Cream
INN or Proposed INN: IMIQUIMOD
CAS Number: 99011-02-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 12.5-

Product Name: idiviualized peptide vaccine
Product Code: iVAC-CLL
Pharmaceutical Form: Injection
INN or Proposed INN: individualized peptide vaccine
CAS Number: 8000019-76-3
Current Sponsor code: individualized peptide vaccine
Other descriptive name: POLYPEPTIDE
Concentration unit: µg/µl microgram(s)/microlitre
Concentration type: equal
Concentration number: 0,6-

Primary Outcome(s)

Main Objective: The aim of this study is to induce a peptide-specific immune
response in CLL patients by multi-peptide vaccination with a
patient-individualized peptide cocktail.

Primary endpoint:
• Induction of peptide-specific T cell responses

Timepoint(s) of evaluation of this end point: The primary objective of this trial is to evaluate the immunogenicity of an individually composed multi-peptide vaccine as determined by induction of T cell immunity. The induction of peptide-specific T cell responses will be determined by IFN? ELISPOT, intracellular cytokine staining and tetramer staining. These assays will be performed after obtaining and processing the last blood sample of each individual patient. All samples will be analyzed in parallel to limit interassay variability. In case of drop out of a patient from the study before 12 months after first vaccination, all so far available samples will be evaluated. Patients will be considered analysable when they received at least one vaccination.

Secondary Objective: • Toxicity and Safety by CTCAE V4.03
• Overall survival at the end of study
• Disease free survival at the end of study
• Remission status at the end of study
• Achievement of MRD-negativity or reduction in MRD+
patients

• Overall survival, disease free survival, remission status
for 5 years after the end of the study (off study)
• Correlation of inducability of immune responses with
clinical and biological patient characteristics

Primary end point(s): • Induction of peptide-specific T cell responses

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: The secondary objectives of this trial are to evaluate the safety and toxicity of the individually composed multi-peptide. Toxicity will be determined by evaluation of the number of adverse events according to CTCAE V 4.03 (Appendix I) and the time schedule for individual vaccine composition.
Further secondary objectives of this trial are the overall survival, the disease free survival and the remission status at the end of study as well as the evaluation of achievement of MRD-negativity or reduction in MRD-positive patients.
For all patients participating in this study progression free survival and overall survival will be asseseds after 3 and 5 years outside the study protocol.

Secondary end point(s): • Toxicity and Safety by CTCAE V4.03
• Overall survival at the end of study
• Disease free survival at the end of study
• Remission status at the end of study
• Achievement of MRD-negativity or reduction in MRD-positive patients
• Overall survival, disease free survival, remission status and MRD level after 3 and 5 years

Secondary ID(s)

iVAC-CLL01

NCT02802943

Source(s) of Monetary Support

University Hospital Tuebingen

Ethics review

Status: Approved
Approval date:
Contact: