Relapsed chronic lymphocytic leukemia MedDRA version: 14.1 Level: PT Classification code 10008958 Term: Chronic lymphocytic leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: NOX-A12
Pharmaceutical Form: Solution for injection
Current Sponsor code: NOX-A12
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 14.66-
Sponsors
NOXXON Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male of female, age = 18 2. Diagnosis of B cell CLL 3. Relapsed, bendamustine-sensitive (response duration of at least 6 months as assessed by prior treating physician) or bendamustine-naive patients after at least one but not more than 3 prior treatment of their disease. 4. CLL in need of treatment (Binet C or A/B with active disease) according to the IWCLL guidelines 5. Subject must have measurable disease according to IWCLL guidelines 6. Pre-study WHO performance status of = 2 and modified cumulative illness rating scale (CIRS) of less than 7 7. Signed and dated, written informed consent 8. Men and women of reproductive potential must agree to follow accepted birth control methods during treatment and for 3 months after completion of treatment 9. Acceptable liver function: bilirubin =1.2 mg/dL, (According to the current approved bendamustine SPC) at screening 10. Acceptable heamatological status: platelet count = 75 x10 9/L, ANC > 1.5 x 10 9/L 11. Acceptable renal function: serum creatinine =1.5 ULN and/or creatinine clearance = 50 ml/min (Cockcroft Gault formula) 12. No clinical significant abnormalities of liver volume, liver heamodynamics or elasticity, measured by abdominal ultrasound. 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 16 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 17
Exclusion criteria
Exclusion criteria: 1. Relapse of B-cell CLL within 6 months after last chemotherapy 2. Subjects who have progressed to more aggressive B-cell cancers such as Richter's syndrome 3. CLL with either deletion of the short arm of chromosome 17 (17p-) or mutations associated with the loss of p53 4. The subject has a history of or is clinically suspicious of cancer related CNS disease 5. Hyperleukocytosis of > 50,000 WBC/µL 6. Autoimmune hemolytic anemia 7. Prior allogeneic stem cell transplant or patients who are considered to be candidates for allo SCT as assessed by their treating physician 8. Patient has a history of other active malignancies within three years prior to study entry, with the exception of: adequately treated in situ carcinoma of the cervix uteri; basal or squamous cell carcinoma of the skin; in situ carcinoma of the bladder; previous malignancy confirmed and surgically resected with curative intent. 9. The patient exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to: uncontrolled systemic infection (viral, bacterial or fungal); diagnosis of fever and neutropenia within 1 week prior to study drug administration 10. Female subject is pregnant or breast feeding 11. Known infection with HIV, active Hepatitis B or Hepatitis C 12. The patient has a history of prior toxicity from bendamustine or rituximab that resulted in permanent discontinuation of treatments. 13. Treatment with other investigational drugs, or participation in another clinical trial within 30 days prior to study drug administration 14. Uncontrolled hypertension (defined as systolic blood pressure (BP) > 160 mmHg or diastolic BP >100mmHg) 15. Myocardial infarction or unstable angina within the past 6 months prior to study drug administration. Heart failure of New York Heart Association functional Class III or IV prior to study drug administration. 16. Systemic illnesses or other severe concurrent disease including alcoholism which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and efficacy of the investigational treatment 17. Known or suspected of not being able to comply with the trial protocol 18. Having previously enrolled in this clinical trial 19. Known hypersensitivity to rituximab or to any of the excipients or to murine proteins 20. History of recurring or chronic infections or underlying conditions which may further predispose patients to serious infections 21. Known hypersensitivity to bendamustine or to mannitol 22. Invasive surgery within 30 days prior to study drug administration.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and tolerability of NOX-A12 alone (pilot group only) and in combination with BR To determine the complete remission (CR) rate;Secondary Objective: To determine the effect of NOX-A12 alone and combined with BR on the mobilization of peripheral blood CD34+ cells and CLL cells To determine the overall response rate (ORR=CR + PR) rate To determine time to event endpoints such as progression free survival (PFS), event free survival (EFS), time to progression (TTP), duration of response (DOR) and overall survival (OS) after treatment with NOX-A12 in combination with BR To determine the plasma concentration of SDF-1 after treatment with NOX-A12 alone (pilot group only) and in combination with BR To determine the pharmacokinetics of NOX-A12 alone (pilot group only) and in combination with BR;Primary end point(s): Safety the safety evaluation will be based on the following assessments: - adverse events - vital signs - 12 lead ECG - laboratory parameters (CBC, platelets, differential WBC count, serum chemistry, coagulation parameters, urinalysis) - immunogenicity - physical examinations Remission Rates Assessment of overall tumour response - as measured by lymphadenopathy, splenamegaly, hepatomegaly, bone marrow cell counts, peripheral platelet and neutophil counts and heamoglobin measurements.;Timepoint(s) of evaluation of this end point: Safety - throughout the treatment period and for 30 days post last dose Efficacy - at the end of Cycle 3 and Cycle 6 of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - mobilization of CD34+ and CLL cells - immunophenotyping and cell surface antigens of CD34+ and CLL cells - disease assessment, as per the primary endpoint - survival free of disease - death - pharmacokinetic analysis of SDF-1 in plasma - pharmacokinetic analysis of NOX-A12 in plasma;Timepoint(s) of evaluation of this end point: Characterisation of circulating blood cells - Pilot group only - Day 1,2 and 4 post first dose. All patients - Day 1 and 2, Cycle 1 and 4 Pharmacokinetic analysis - Pilot group only - Day 1, 2 and 4 post first dose. All patients - Day 1 Cycle 1 and 4 Progression - 12 weekly intervals for 30 months post end of treatment | — |
Countries
Austria, Belgium, Germany, Italy
Contacts
Public ContactClinical Operations
AMS Advanced Medical Services
Outcome results
None listed