A clinical study on safety, immune activation and the effect of treatment with histamine and IL- 2 in adult tyrosine kinase inhibitor-treated patients with chronic myeloid leukemia (CML )
- Conditions
- Chronic Myeloid Leukemia (CML)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-002728-94-SE
- Lead Sponsor
- Sahlgrenska University Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 15
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
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 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the safety of Ceplene/Proleukin in CML during TKI (Tyrosine kinase inhibitor) treatment.;Secondary Objective: To evaluate the efficacy of HDC/IL-2 treatment in CML.<br>To investigate the immunological effects of HDC/IL-2 in patients with CML.<br>;Primary end point(s): Adverse events as defined by CTCAE v4.03.;Timepoint(s) of evaluation of this end point: 18 weeks after study entry
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Clinical response and hematological improvement, and durations thereof, as determined as reduced BCR/ABL1 levels.<br>2. The quantitative and qualitative effects of HDC/IL-2 on immune cell phenotypes and function.<br>3. Disease progression according to IWG criteria<br>4. Survival.<br>;Timepoint(s) of evaluation of this end point: 1. 18 weeks after study entry<br>2. 18 weeks after study entry<br>3. 2 years after study entry<br>4. 2 years after study entry