Content - CLL 13

CLL 13 - Investigation into the efficacy of three combination therapies compared with standard chemotherapy

Chronic lymphocytic leukaemia (CLL) is a form of leukaemia that usually progresses very slowly. The majority of those affected develop the condition between the ages of 65 and 75. CLL is the most common type of leukaemia in adults in the western world.

Patients with chronic lymphocytic leukaemia who are physically fit can take part in this clinical trial. We are investigating whether treatment with combined medications without standard chemotherapy is more effective and produces fewer side-effects than standard chemotherapy treatment.

We hope that patients treated with venetoclax and rituximab or obinutuzumab, possibly also combined with ibrutinib, will respond better to the therapy and have a longer disease-free period. All of the medicines used in the trial are authorized in either the USA or the EU for the treatment of CLL, although not all of them as a first-line therapy or not in the combinations used in the trial.

Study Chair:

Dr. med. Michael Gregor, Cantonal Hospital Lucerne, +41 41 205 53 13

  • Contacts at the hospitals

  • Inclusion Criteria

    • Documented CLL requiring treatment according to iwCLL criteria.
    • Age at least 18 years.
    • Life expectancy ≥ 6 months.
    • Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements.
    • Adequate bone marrow function indicated by a platelet count >30x10^9/l (unless directly attributable to CLL infiltration of the bone marrow, proven by bone marrow biopsy).
    • Creatinine clearance ≥70ml/min directly measured with 24hr urine collection or calculated according to the modified formula of Cockcroft and Gault (for men: GFR ≈ ((140 - age) x bodyweight) / (72 x creatinine),for women x 0, 85). Dehydrated patients with an estimated creatinine clearance less than 70 ml/min may be eligible if a repeat estimate after adequate hydration is > 70 ml/min.
    • Adequate liver function as indicated by a total bilirubin≤ 2 x, AST/ALT ≤ 2.5 x the institutional ULN value, unless directly attributable to the patient’s CLL or to Gilbert’s Syndrome.
    • Negative serological testing for hepatitis B (HBsAg negative and anti-HBc negative; patients positive for anti-HBc may be included if PCR for HBV DNA is negative and HBV-DNA PCR is performed every month until 12 months after last treatment cycle), negative testing for hepatitis C RNA within 6 weeks prior to registration.
    • Eastern Cooperative Oncology Group Performance Status (ECOG) performance status 0-2.
  • Exclusion Criteria

    • Any prior CLL-specific therapies (except corticosteroid treatment administered due to necessary immediate intervention; within the last 10 days before start of study treatment, only dose equivalents of 20 mg prednisolone are permitted). 
    • Transformation of CLL (Richter transformation).
    • Decompensated hemolysis, defined as ongoing hemoglobin drop in spite of three more concurrent treatments being administered for hemolysis
    • Detected del(17p) or TP53 mutation.
    • Patients with a history of PML.
    • Any comorbidity or organ system impairment rated with a single CIRS (cumulative illness rating scale) score of 4 (excluding the eyes/ears/nose/throat/larynx organ system), a total CIRS score of more than 6 or any other life-threatening illness, medical condition or organ system dysfunction that, in the investigator´s opinion, could comprise the patients safety or interfere with the absorption or metabolism of the study drugs (e.g, inability to swallow tablets or impaired resorption in the gastrointestinal tract).
    • Urinary outflow obstruction.
    • Malignancies other than CLL currently requiring systemic therapies, not being treated in curative intention before (unless the malignant disease is in a stable remission due to the discretion of the treating physician) or showing signs of progression after curative treatment.
    • Uncontrolled or active infection.
    • Patients with known infection with human immunodeficiency virus (HIV).
    • Requirement of therapy with strong CYP3A4 and CYP3A5 inhibitors/inducers.
    • Anticoagulant therapy with warfarin or phenoprocoumon, (rotation to alternative anticoagulation is allowed, but note that patients being treated with NOAKs can be included, but must be properly informed about the potential risk of bleeding under treatment with ibrutinib).
    • History of stroke or intracranial hemorrhage within 6 months prior to registration.
    • Use of investigational agents which might interfere with the study drug within 28 days prior to registration.
    • Vaccination with live vaccines 28 days prior to registration.
    • Major surgery less than 30 days before start of treatment.
    • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, known sensitivity or allergy to murine products.
    • Known hypersensitivity to any active substance or to any of the excipients of one of the drugs used in the trial.
    • Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment; further pregnancy testing will be performed regularly).
    • Fertile men or women of childbearing potential unless:
      • surgically sterile or ≥ 2 years after the onset of menopause
      • willing to use two methods of reliable contraception including one highly effective contraceptive method (Pearl Index <1) and one additional effective (barrier) method during study treatment and for 18 months after the end of study treatment.
    • Legal incapacity.
    • Prisoners or subjects who are institutionalized by regulatory or court order.
    • Persons who are in dependence to the sponsor or an investigator.

Locations for this trial:

Kantonsspital Aarau
Tellstrasse 25
0 5001 Aarau
Kantonsspital Baden
Im Ergel 1
4600 Baden
Universitätsspital Basel
Petersgraben 4
0 4031 Basel
Istituto Oncologico della Svizzera Italiana IOSI
Via Ospedale
0 6500 Bellinzona
Inselspital
Freiburgstrasse 8
3010 Bern
Kantonsspital Graubünden
Loëstrasse 170
7000 Chur
Hôpitaux Universitaires de Genève HUG
Rue Gabrielle-Perret-Gentil 4
0 1205 Genève
Kantonsspital Liestal
Rheinstrasse 26
0 4410 Liestal
Kantonsspital Luzern
Spitalstrasse
0 6000 Luzern
Kantonsspital Olten
Baslerstrasse 150
0 4600 Olten
Kantonsspital Muensterlingen
Spitalcampus 1
0 8596 Münsterlingen
Kantonsspital St. Gallen
Rorschacher Strasse 95
0 9007 St. Gallen
Kantonsspital Winterthur
Brauerstrasse 15
0 8401 Winterthur
Stadtspital Triemli
Birmensdorferstrasse 497
0 8063 Zürich
UniversitätsSpital Zürich
Rämistrasse 100
0 8091 Zürich