Relapsed Chronic lymphocytic leukaemia (CLL) MedDRA version: 21.1 Level: PT Classification code 10008958 Term: Chronic lymphocytic leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Fludara
Pharmaceutical Form: Concentrate for solution for infusion
Trade Name: Endoxan
Product Name: Cyclophosphamide
Product Code: 1001995601
Pharmaceutical Form: Concentrate for solutio
Sponsors
Städtisches Klinikum München GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis of CLL in need of treatment according to the iwCLL guidelines 8 2. Relapsed or refractory disease after at least one, but no more than 3 prior regimens for CLL 3. Medically fit patients without relevant comorbidity, defined as total CIRS score =6 (single score 60 ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured after 24 h urine collection 7. Adequate liver function as indicated by a total bilirubin, AST, and ALT =2 the institutional ULN value, unless directly attributable to the patient’s CLL 8. Negative serological Hepatitis B test (i.e. HBsAg negative and anti-HBc negative, patients positive for anti-HBc may be included if PCR for HBV DNA is negative); negative testing of Hepatitis C RNA; negative HIV test within 6 weeks prior to registration 9. 18 years of age or older 10. Life expectancy >6 months 11. Able and willing to provide written informed consent and to comply with the study protocol procedures 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 58 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 58
Exclusion criteria
Exclusion criteria: 1. Detected del817p) or TP53 mutation 2. Refractoriness to FCR/BR 3. Transformation of CLL to aggressive NHL (Richter’s transformation) 4. Known central nervous system (CNS) involvement 5. Evidence of significant uncontrolled concomitant disease 6. Major surgery < 30 days before screening 7. Decompensated hemolytic anemia 28 days before screening 8. Hemolytic cystitis 28 days before screening 9. Patients with a history of confirmed PML 10. Prior treatment with GA101 11. History of prior malignancy, except for conditions as listed below (a-d) and if patients have recovered from the acute side effects incurred as a result of previous therapy: a. Malignancies treated with curative intent and with no known active disease present for = 2 years before randomization b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease at screening c. Adequately treated cervical carcinoma in situ without evidence of disease at screening d. Surgically adequately treated low grade, early stage localized prostate cancer without evidence of disease at screening 12. Use of investigational agents or concurrent anti-cancer treatment within the last 4 weeks before registration 13. Patients with active infection requiring systemic treatment 14. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies and/ or known sensitivity or allergy to murine products 15. Hypersensitivity to fludarabine, cyclophosphamide, bendamustine, GA101 and/ or to any of the excipients for example mannitol 16. An individual organ/ system impairment score of 4 as assessed by the CIRS definition limiting the ability to receive an intensive therapy for CLL 17. Legal incapacity 18. Women who are pregnant or lactating 19. Fertile men or women of childbearing potential unless: a. surgically sterile or =2 years after the onset of menopause b. willing to use a highly effective contraceptive method (Pearl Index <1) during study treatment and for 12 months after end of study treatment 20. Vaccination with a live vaccine within a minimum of 28 days before screening 21. Participation in any other clinical trial which would interfere with study drug 22. Prisoners or subjects who are institutionalized by regulatory or court order 23. Persons who are in dependence to the sponsor or an investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Main objective of the trial ist to evaluate the efficacy of two regimens of immunochemotherapy, i.e. Fludarabine, Cyclophosphamide plus GA101 (FCG) and Bendamustine plus GA101 (BG), in patients with relapsed or refractory CLL.;Secondary Objective: - To evaluate the safety of the regime of immunochemotherapies, i.e. Bendamustine plus GA101 (BG) in patients with relapsed or refractory CLL followed by maintenance therapy with GA101 for responding patients. - To investigate the feasibility of a maintenance therapy with GA101 following either a regimen of BG for responding patients. - To evaluate descriptively safety and efficacy of the BG regimen in patients with relapsed or refractory CLL.;Primary end point(s): Best overall response rate (ORR) defined as best response assessed until and including response assessment at follow up 2 (6 months after final restaging/ induction), defined by the proportion of patients having achieved a CR/ CRi, clinical CR/ CRi or nPR/ PR as best response based on the respective population (= number of patients with best response CR/ CRi, clinical CR/ CRi or nPR/ PR divided by the number of the respective population);Timepoint(s) of evaluation of this end point: The analysis of the primary endpoint will be performed 60 months after the last patient was randomized. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • MRD levels during treatment and maintenance • Progression free survival (PFS) • Event-free survival (EFS) • Overall survival (OS) • Overall response to maintenance treatment • Duration of response in patients with CR/ CRi, clinical CR / clinical CRi or nPR/ PR • Time to next anti-leukemia treatment • Overall response rate in biological defined risk groups • Complete response rate • Safety parameters during induction and maintenance phase [type, frequency, and severity of adverse events (AEs), AESI (AEs of special interest) and relationship of AEs to study treatment] • Evaluation of relationship between various baseline markers and clinical outcome parameters;Timepoint(s) of evaluation of this end point: The analysis of the primary endpoint will be performed 60 months after the last patient was randomized. | — |
Countries
Germany
Contacts
Public ContactEmily van der Poel-Holmes
Deutsche CLL Studiengruppe
Outcome results
None listed