Personalized Multi-peptide Vaccination in CLL Patients

Prior treatment

• Participation in any clinical study or having taken any investigational therapy which would interfere with the study primary and secondary end points.
• Any immunosuppressive treatment not related to CLL except corticosteroids

Other illness

• Disease transformation (active), i.e. Richter's syndrome, prolymphocytic leukemia.
• Autoimmune hemolysis or immune thrombocytopenia caused by CLL
• Pre-existing auto-immune disease except for Hashimoto thyroiditis and mild (not requiring immunosuppressive treatment) psoriasis
• Chronic lung disease requiring drug treatment

Age

• 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)

Other

• Pregnant or lactating females.
• Treatment regimes without ibrutinib
• Ibrutinib-related side effects \> CTC grade 2 (CTCAE V5.0)

• Documented diagnosis of CLL according to iWCLL guidelines
  • For Screening phase:
• CLL that warrants treatment (according to modified criteria for initiation of therapy):
• Massive (ie, lower edge of spleen ≥ 6 cm below the left costal margin), progressive, or symptomatic splenomegaly, or
• Massive (ie, ≥ 10 cm in the longest diameter), progressive, or symptomatic lymphadenopathy, or
• Progressive lymphocytosis in the absence of infection, with an increase in blood ALC ≥ 50% over a 2-month period or lymphocyte doubling time of \< 6 months (as long as initial ALC was ≥ 30,000/L), or
• Autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy, or -Constitutional symptoms, defined as any one or more of the following disease- related symptoms or signs occurring in the absence of evidence of infection:
  • Unintentional weight loss of ≥ 10% within the previous 6 months, or
  • Significant fatigue (≥ Grade 2), or
  • Fevers \> 38.0°C for ≥ 2 weeks, or
  • Night sweats for \> 1 month.
• Planned initiation of a ibrutinib-based regime (monotherapy or cominational therapy (e.g. anti-CD20))
  • For Vaccination phase:
• Ongoing ibrutinib therapy (monotherapy).
• Achievement of a response (at least PR according to iWCLL guidelines)
• MRD positivity (CLL cells in peripheral blood ≥ 10-4, determined by flow cytometry, Labor Kiel, Prof. Brüggemann).
• Negative SARS-CoV-2 test (as long as WHO declares pandemic spread of SARS-CoV-2)
• Prior ibrutinib treatment of at least 6 months and not longer than 8 months.
  • HLA typing positive for any of the following HLA alleles: HLA-A\*02, A\*24, B\*07.
  • Ability to understand and voluntarily sign an informed consent form.
  • Ability to adhere to the study visit schedule and other protocol requirements.
  • Age ≥ 18 years at the time of signing the informed consent form.
  • ECOG performance status score of ≤ 2.
  • Negative serological Hepatitis B test or negative PCR in case of positive serological test without evidence of an active infection, negative testing of Hepatitis C RNA, negative HIV test within 6 weeks prior to study inclusion.
  • Female patients of childbearing potential (FCBP) and male volunteers with partners of child bearing potential, who are sexually active, must agree to the use of two effective forms (at least one highly effective method) of contraception. This should be started from the signing of the informed consent and continue throughout period of study
  • Postmenopausal or evidence of non-childbearing status. For FCBP: negative urine or serum pregnancy test within 14 days prior to study treatment.
  • Postmenopausal or evidence of non-childbearing status is defined as:
• Amenorrhoeic for 1 year or more following cessation of exogenous hormonal treatments
• Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50