E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) after first line therapy |
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E.1.1.1 | Medical condition in easily understood language |
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) after first line therapy |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009310 |
E.1.2 | Term | CLL |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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
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E.2.2 | Secondary objectives of the trial |
• 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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 IFNγ 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. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Induction of peptide-specific T cell responses |
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E.5.1.1 | 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 IFNγ 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. |
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E.5.2 | 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 |
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E.5.2.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Phase II multicentric open label interventional clinical trial, Patient stratification:MRD- and MRD+ |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The End of Study for a patient enrolled in this trial is defined as time of last follow-up at 6 months. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |