Main info

Identifier:

HOVON 507 CLL / CLL18

Sponsor:

GCLLSG

Working group party:

CLL

Age:

>= 18

Stage:

1st Line

Echelon:

Limited Site Selection

Active sites:

0

(of 1)

15 sites are pending

Title:

Timeline

Details

Phase:

Prospective randomized Phase III study

Monitoring Type:

Study Specific

Objectives:

Primary study objective

• To compare the efficacy of MRD-guided Venetoclax/Pirtobrutinib vs fixed-duration (15 cycles) Venetoclax/Pirtobrutinib and MRD-guided Venetoclax/Pirtobrutinib vs. fixed-duration (12 cycles) Venetoclax/Obinutuzumab by measuring progression-free survival (PFS) in patients with previously untreated chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL).

Secondary objectives

• To evaluate MRD levels by different types of measurement from different materials at the final restaging (three months after end of treatment) and at selected other time points
• To evaluate ORR as assessed by iwCLL guidelines at the final restaging (three months after end of treatment) and at selected other time points
• To evaluate CR rate as assessed by iwCLL guidelines at the final restaging (three months after end of treatment) and at selected other time points
• To evaluate best response as assessed by iwCLL guidelines until one year after end of treatment
• To evaluate duration of response (DOR) as assessed by iwCLL guidelines
• To evaluate time to next treatment (TTNT)
• To evaluate treatment-free survival (TFS)
• To evaluate overall survival (OS)
• To evaluate the safety and tolerability of MRD-guided Ven-Pirto, fixed-duration VenPirto, and fixed-duration Ven-Obi

Eligibility

Inclusion Criteria:

To be eligible to participate in this trial, an individual must meet all the following criteria:

• 1. Documented CLL/SLL requiring treatment according to iwCLL criteria73 with a CLL phenotype cell count >10-2 tracked by flow cytometry at screening.
• 2. Adequate bone marrow function as indicated by:
  • an absolute neutrophil count ≥1 x 10⁹/l
  • a haemoglobin value ≥8.0 g/dl without transfusions during the last 7 days unless directly attributable to CLL/SLL (e.g. bone marrow infiltration) and
  • a platelet count ≥25 x 10⁹/l unless due to the CLL/SLL, in this case, platelet count should be ≥ 10000/µl without transfusion during the last 7 days.
• 3. Adequate renal function, as indicated by a creatinine clearance ≥30 ml/min calculated according to the MDRD-formula75 or an equally accurate method (e.g. 24 hr. urine collection)
• 4. Adequate liver function as indicated by:
  • a total bilirubin ≤2 x the institutional upper limit of normal (ULN) value, and
  • AST/ ALT1 ≤2.5 x the institutional ULN value,

unless directly attributable to the patient’s CLL/SLL or to Gilbert’s Syndrome.

• 5. 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 monthly until 12 months after last dosage of obinutuzumab), negative testing for hepatitis-C (HCV-RNA PCR) and negative HIV test within 6 weeks prior to registration
• 6. Age ≥18 years
• 7. Eastern Cooperative Oncology Group Performance Status (ECOG) performance status 0-2
• 8. Life expectancy ≥6 months
• 9. Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this trial:

• 1. Any prior CLL- or SLL-specific therapies1, except for 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 per day are permitted).
• 2. Decompensated auto-immune cytopenia (defined as ongoing drop in haemoglobin [AIHA] or in platelets [ITP] in spite of prednisolone and/or intravenous immunoglobulins treatment).
• 3. (Suspicion of) transformation of CLL/SLL (i.e. Richter transformation) or central nervous system (CNS) involvement.
• 4. (Suspicion of) progressive multifocal leukoencephalopathy (PML).
• 5. Malignant neoplasm other than CLL/SLL unless in remission and unlikely to adversely impact on patient´s life expectancy, defined as curatively treated non-melanoma skin cancer or other neoplasias treated curatively ≥1 year ago, without signs of progression and not currently requiring systemic therapies (with the exception of ongoing anti-hormonal therapy).
• 6. Active infection requiring systemic treatment, including HIV, HBV and HCV * 7. Increased risk of bleeding, e.g. due to:
  • known bleeding disorder2
  • anticoagulant therapy with phenprocoumon or other vitamin K antagonists (anticoagulation with a direct oral Xa or thrombin inhibitor [DOAC] or heparin is permitted)
  • major surgery ≤4 weeks prior to randomisation
  • stroke or intracranial haemorrhage ≤6 months of randomisation
• 8. Any comorbidity or organ system impairment rated with a CIRS (cumulative illness rating scale) score of 4 or any other life-threatening illness, medical condition or organ system dysfunction that – in the investigator´s opinion - could compromise the patient`s safety3 or interfere with the absorption or metabolism of the study drugs (e.g, inability to swallow tablets or impaired resorption in the gastrointestinal tract)
• 9. Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment)
• 10. Fertile men or women of childbearing potential unless:
  • surgically sterile or ≥2 years after the onset of menopause, or
  • willing to use two methods of reliable contraception including one highly effective (Pearl Index <1) and one additional effective (barrier) method during study treatment and for the required time period thereafter (at least one and up to 18 months after end of study treatment depending of study drug(s) used, see chapter 2.2.2.1 Known risks relevant with all study drugs).
• 11. Vaccination with a live vaccine ≤28 days prior to registration

Registration Details

Participating Sites

= Active hospitals

= Inactive hospitals