E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Myeloid Leukemia (CML) |
Kronisk myeloisk leukemi (KML) |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic Myeloid Leukemia (CML) |
Kronisk myeloisk leukemi (KML) |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety of Ceplene/Proleukin in CML during TKI (Tyrosine kinase inhibitor) treatment. |
Att undersöka säkerhetsprofilen för Ceplene/Proleukin-behandling vid samtida behandling med tyrosinkinashämmare. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of HDC/IL-2 treatment in CML. To investigate the immunological effects of HDC/IL-2 in patients with CML.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients are able to provide written informed consent 2. Patients must have CML treated with TKI for at least 24 months, with no therapy change during the last 6 months or planned therapy change within 6 months, and be in cytogenetic remission, which is defined by the presence of all of the following criteria: •Ph+ or variants must have been demonstrated by BM cytogenetics, FISH or PCR at diagnosis • Complete hematological remission for at least 12 months prior to inclusion • Complete cytogenetic remission on latest bone marrow examination. • Minimum 2 RQ-PCR determination below 1% on the IS, i.e. MR2 during the last 12 months. 3. ECOG Performance Status (PS) Score 0 - 1 (see Appendix 2) 4. Adequate hepatic function defined as: total bilirubin ≤ 2.0 times the institutional upper limit of normal (ULN) in absence of Gilbert type unconjugated hyperbilirubinemia; alanine aminotransferase (ALAT≤ 2.5 times the institutional ULN. 5. Adequate renal function defined as serum creatinine ≤ 2 times the institutional ULN. 6. Men and women, ages 18 years and older. 7. Potentially fertile women must use an adequate method of contraception to avoid pregnancy throughout the study. 8. Potentially fertile women must have a negative serum or urine pregnancy test
|
|
E.4 | Principal exclusion criteria |
For entry into the study, none of the exclusion criteria can be met. 1. Fertile women who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study 2. Women who are pregnant or breastfeeding. 3. Men with fertile sexual partners who can or will not use an acceptable contraception method for the entire study 4. A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy. 5. Class III or IV cardiac disease, hypotension or severe hypertension, vasomotor instability, serious or uncontrolled cardiac dysrhythmias (including ventricular arrhythmias) at any time, acute myocardial infarction within the past 12 months, active uncontrolled angina pectoris or symptomatic arteriosclerotic blood vessel disease. 6. Prior or concurrent malignancy, except for the following: • adequately treated basal cell or squamous cell skin cancer • cervical carcinoma in situ • adequately treated Stage I or II cancer from which the subject is currently in complete remission • any other cancer from which the subject has been disease-free for three years. 7. Severe psychiatric illness, imprisonment or mental impairment inflicting on ability to give informed consent. 8. Abuse of alcohol, prescribed or illicit drugs 9. History of seizures, central nervous system disorders, stroke within the last 12 months, or psychiatric disability thought to be clinically significant in the opinion of the Investigator and adversely affecting compliance to protocol. 10. Patients unable to undergo repeat treatments, clinical evaluations and other diagnostic procedures required by the protocol. 11. Active autoimmune disease (including but not limited to systemic lupus, inflammatory bowel disease, and psoriasis). 12. Patients with active peptic or esophageal ulcer disease or with past peptic ulcer or esophageal disease with a history of bleeding. 13. Patients requiring active treatment for hypotension. 14. Medical, sociologic, or psychological impediment to probable compliance with the protocol. 15. Patients unable to stop therapy with H2 antagonists, antihistamines, clonidine, corticosteroids or immunomodulating agents. These drugs should discontinued at least 24 hours prior to initiation of HDC/IL2 therapy and patients should not receive H2 antagonists throughout treatment. 16. Patients with a history of hypersensitivity to histamine or histamine products, severe allergies to food or contrast media requiring treatment within the last five years.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Adverse events as defined by CTCAE v4.03. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
18 weeks after study entry |
|
E.5.2 | Secondary end point(s) |
1. Clinical response and hematological improvement, and durations thereof, as determined as reduced BCR/ABL1 levels. 2. The quantitative and qualitative effects of HDC/IL-2 on immune cell phenotypes and function. 3. Disease progression according to IWG criteria 4. Survival.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. 18 weeks after study entry 2. 18 weeks after study entry 3. 2 years after study entry 4. 2 years after study entry |
|
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 | Yes |
E.6.13.1 | Other scope of the trial description |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
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 | No |
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.8.3 |
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 | 2 |
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 | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |