Main info

Identifier:

HO500 CLL

Sponsor:

GCLLSG

Working group party:

CLL

Age:

>= 18

Stage:

1st Line

Echelon:

Level D

Included patients:

901

(of 897)

Active sites:

25

(of 26)

Title:

A phase 3 multicentre, randomized, prospective, open-label trial of ibrutinib monotherapy versus fixed-duration venetoclax plus obinutuzumab versus fixed-duration ibrutinib plus venetoclax in patients with previously untreated chronic lymphocytic leukaemia (CLL)

Timeline

News

Flow

Details

Phase:

Prospective Phase III study

Monitoring Type:

Study Specific

Objectives:

The primary objective of the study is to compare the efficacy of continuous ibrutinib monotherapy with fixed-duration venetoclax plus obinutuzumab and fixed-duration ibrutinib plus venetoclax by measuring progression-free survival (PFS) in patients with previously untreated CLL.

Eligibility

Inclusion Criteria:

• Documented CLL/Small lymphocytic lymphoma (SLL) 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 independent of growth factor or transfusion support within 2 weeks of screening initiation as follows, unless cytopenia is due to CLL:
  • Absolute neutrophil count ≥ 1.0 × 109/L
  • Platelet counts ≥ 30 × 109/L; in cases of thrombocytopenia clearly due to CLL (per the discretion of the investigator), platelet count should be ≥ 10 × 109/L
  • Total haemoglobin ≥ 8 g/dL (without transfusion support, unless anaemia is due to CLL)
• GFR >30ml/min directly measured with 24hr urine collection, 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) or an equally accurate method.
  • For patients with creatinine values within the normal range the calculation of the clearance is not necessary. Dehydrated patients with an estimated creatinine clearance less than 30ml/min may be eligible if a repeat estimate after adequate hydration is > 30 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), and for hepatitis C (anti-HCV-ab negative; in case of positive HCV anti-body test, negative HCV-PCR is required).
• 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 up to 20 mg prednisolone are permitted).
• Transformation of CLL (Richter transformation). When Richter transformation is suspected, PET-CT and/or biopsy should be performed to rule out transformation.
• Patients with a history of PML.
• An individual organ/ system impairment score of 4 as assessed by the CIRS definition limiting the ability to receive the study treatment or any other life-threatening illness, medical condition or organ system dysfunction that, in the investigator´s opinion, could compromise 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).
• Malignancies other than CLL currently requiring systemic therapies, not being treated with curative intent 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 (incl. up to 7 days prior to study treatment start).
• Anticoagulant therapy with warfarin or phenprocoumon, (alternative anticoagulation is allowed (e.g. DOACs), but patients 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 for study screening.
• Known bleeding disorders
• Child B / C liver cirrhosis
• Use of investigational agents which might interfere with the study drug within 28 days prior to registration for study screening.
• Vaccination with live vaccines 28 days prior to registration for study screening.
• Major surgery less than 30 days before start of study 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 study treatment; further pregnancy testing will be performed monthly).
• 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.

Registration Details

Participating Sites

= Active hospitals

= Inactive hospitals