Chronic myeloid leukemia MedDRA version: 21.0 Level: LLT Classification code 10009016 Term: Chronic myeloid leukemia in remission System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Besremi
Product Name: AOP2014
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: Ropeginterferon alfa-2b
CAS Number: 13350985040
Other descriptive name: MON
Sponsors
Philipps University Marburg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Signed written informed consent form 2.Capability and willingness to comply with study procedures and ability to self-administration of the study drug 3.Male or female aged = 18 years 4.At least three years of TKI therapy 5.BCR-ABL-positive, chronic phase CML patients with a transcript level according to the international scale (IS) of at least MR4, or better (MR4.5, MR5). MR4 is defined as (i) detectable disease =0.01% BCR-ABL IS or (ii) undetectable disease in cDNA with =10,000 ABL or =24,000 GUS transcripts for at least one year. There have to be at least three consecutive PCR-results with MR4 or better within the last year (+ 2 months) before study entry. The latest of these PCRs must be a confirmatory MR4 measurement prior to randomization by the EUTOS-certified Study Reference Laboratories for PCR (BCR-ABL mRNA). No PCR-results in the last year before randomization can be worse than MR4. If the last PCR was not done within last two months from baseline (day 0) in an EUTOS-certified Study Reference Laboratory, the PCR sample must be sent to an EUTOS-certified Study Reference Laboratory at screening. 6.Patients who had failed to discontinue TKI in a prior discontinuation attempt are eligible for this protocol, if they fulfil criterion 5 after retreatment with TKI. A prior TKI discontinuation failure must be specifically indicated at inclusion and documented 7.Adequate organ function: especially total bilirubin, lactate dehydrogenase [LDH], aspartate aminotransferase [AST], alanine aminotransferase [ALT] and coagulation parameters = 2 × upper limit of normal (ULN) 8.Adequate hematological parameters: platelet count =100×1000000000/L; white blood cell count =2.5×1000000000/L; lymphocytes =1.0×1000000000/L; hemoglobin=9.0 g/dL or 5.59 mmol/L 9.Female patients with reproductive potential must agree to maintain highly effective methods of contraception by practicing abstinence or by using at least two methods of birth control from the date of consent through the end of the study. If abstinence could not be practiced, a combination of hormonal contraceptive (oral, injectable, or implants) and a barrier method (condom, diaphragm with a vaginal spermicidal agent) has to be used. Male patients must agree to use condoms during study participation. 10.Negative serum pregnancy test in women of childbearing potential. 11.Date of diagnosis of CML confirmed by laboratory PCR must be known. 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 150 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 60
Exclusion criteria
Exclusion criteria: 1.Rare variants of BCR-ABL not quantifiable by RT-PCR according to the international scale (IS) 2.Current or previous autoimmune diseases requiring treatment 3.Immunosuppressive treatment of any kind, tranplant recipients 4.Prior allogeneic stem cell transplantation 5.Prior pegylated IFN therapy. Prior low dose conventional IFN treatment with = 3 x 3 Mio I.E. / week for less than 1 year is acceptable 6.History of TKI resistance within the last 4 years of TKI therapy 7.History of accelerated phase or blast crisis 8. Hypersensitivity/allergy to the active substance or excipients of the formulation 9.Severe hepatic dysfunction or decompensated cirrhosis 10.End stage renal disease (GFR<15ml/min) 11.Thyroid disease that cannot be controlled by conventional therapy 12 Uncontrolled diabetes mellitus 13.Epilepsy or other disorders of the central nervous system 14.Severe cardiac disease history including unstable or uncontrolled cardiac disease in the previous 6 months 15.Uncontrolled hypertension 16.Any history of retinopathy e.g. retinal detachment, degeneration or thromboembolic events 17.Clinically significant concomitant diseases or conditions, which, in the opinion of the investigator, would lead to an unacceptable risk for the patient to participate in the study (please refer also to the actual Investigator Brochure) 18.Other malignancy, except adequately treated superficial bladder cancer, basal or squamous cell carcinoma of the skin, or other cancer(s) for which the patient has been disease free for more than 3 years 19.Active or uncontrolled infections at the time of randomization 20.Pregnant and/or nursing women 21.Use of antibiotic therapy within the last 2 weeks prior to randomization 22.Concurrent use of molecular targeted therapy 23.Tested HIV sero-positivity or tested active hepatitis B or C infection 24.Participation in another clinical study with other investigational drugs within 14 days prior to randomization 25.Vaccination within 1 month prior to randomization 26.Any medical, mental, psychological or psychiatric condition (particularly severe depression, suicidal ideation or suicide attempt) that in the opinion of the investigator would not permit the patient to complete the study or comply to study procedures 27.Drug and/or alcohol abuse
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of AOP2014 administered bi-weekly subcutaneously (s.c.) in preventing molecular relapse (loss of MMR) in CML patients, who discontinue ABL tyrosine kinase inhibitor therapy (TKI) in deep molecular remission of MR4 or better (MR4.5, or MR5).;Secondary Objective: Secondary Objectives: To assess tolerability and toxicity of AOP2014 To assess quality of life before and after TKI discontinuation To evaluate the safety of maintenance therapy with AOP2014 To assess overall survival For Germany: To explore the value of 95 CD86+pDC / 100000 lymphocytes at baseline in predicting risk of molecular relapse (loss of MMR) For Germany:Explore immunological and genetic biomarkers to study biology of TFR, and identify predictors IFN response. Evaluation of cytokines/chemokines (i.e., IL-6, IFN-a, IL 10, and others) ;Primary end point(s): The primary efficacy endpoint is molecular relapse free survival (mRFS).;Timepoint(s) of evaluation of this end point: At the final analysis 7 months after randomization of the last patient. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • mRFS 7 months after randomization • mRFS 13 months after randomization • mRFS 25 months after randomization • Safety, tolerability and toxicity based on incidences of adverse events, serious adverse events • Quality of life (QoL) • For Germany: To explore the value of 95 CD86+pDC / 100000 lymphocytes at baseline (before TKI stop) as a predictor of RFS • Overall survival • For Germany: Explore immunological and genetic biomarkers to study biology of TFR, and identify predictors IFN response • For Germany: Evaluation of cytokines/chemokines (i.e., IL-6, IFN-a, IL 10, and others) • Kinetics of BCR-ABL transcript level over time after TKI stop;Timepoint(s) of evaluation of this end point: 7, 13 and 25 months after randomization | — |
Countries
France, Germany
Contacts
Public ContactKKS Marburg
Koordinierungszentrum für Klinische Studien der Philipps-Universität Marburg
Outcome results
None listed