Fixed-duration treatment for chronic lymphocytic leukemia with ibrutinib and obinutuzumab

Fixed-duration Therapy With Ibrutinib and Obinutuzumab (GA-101) in Treatment-naïve Patients With CLL

This study is testing a new treatment plan using ibrutinib and obinutuzumab for people with chronic lymphocytic leukemia who haven't been treated before, to see if it can help them reach a point where the disease is undetectable in their bone marrow.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 53 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: IRCCS San Raffaele (other)
• Drugs / interventions: chemotherapy, obinutuzumab, ibrutinib
• Locations: 1 site (Milan, MI)
• Trial ID: NCT04908228 on ClinicalTrials.gov

What this trial studies

This phase 2 multicenter interventional study aims to evaluate the efficacy of a fixed-duration therapy combining ibrutinib and obinutuzumab in treatment-naïve patients with chronic lymphocytic leukemia (CLL). Patients will receive ibrutinib daily for 24 months, with obinutuzumab administered starting from the 13th cycle. The primary endpoint is to assess the undetectable minimal residual disease (uMRD) in the bone marrow at the end of treatment, followed by a 30-day follow-up. If patients experience disease relapse after treatment, ibrutinib will be reintroduced at the standard dose.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with untreated active chronic lymphocytic leukemia requiring treatment.

Not a fit: Patients with chronic lymphocytic leukemia who have previously received treatment or have significant comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with chronic lymphocytic leukemia, potentially leading to better disease control.

How similar studies have performed: Other studies have shown promising results with similar combinations of targeted therapies in CLL, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 years
2. Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that meets iwCLL diagnostic criteria
3. Previously untreated active disease requiring treatment per iwCLL criteria
4. ECOG PS 0 or 1
5. Measurable lymph node disease (\>1.5 cm longest diameter) by CT scan
6. Adequate hematologic function defined as:

   1. Absolute neutrophil count (ANC) \>750 cells/μL (750 cells/mm3 or 0.75 x 109/L)
   2. Platelet count \>30,000/μL (30,000 cells/mm3 or 30 x 109/L)
   3. Hemoglobin \>8.0 g/dL
7. Adequate hepatic and renal function defined as:

   1. Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤3.0 x upper limit of normal (ULN)
   2. Estimated Creatinine Clearance (CrCl) ≥30 mL/min (Cockcroft- Gault)
   3. Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
8. Prothrombin time (PT)/International normal ratio (INR) \<1.5 x ULN and PTT (activated partial thromboplastin time \[aPTT\]) \<1.5 x ULN (unless abnormalities are unrelated to coagulopathy or bleeding disorder).

Exclusion Criteria:

Any prior therapy (including but not limited to chemotherapy, targeted therapy, immunomodulating therapy, radiotherapy, and/or monoclonal antibody) used for treatment of CLL or SLL.

2\. Patients carrying del(17p) and/or TP53 mutation as assessed by central laboratory.

3\. History of other malignancies, except:

1. Malignancy treated with curative intent and with no known active disease present for ≥3 before the first dose of study drug and felt to be at low risk for recurrence by the treating physician
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
3. Adequately treated carcinoma in situ without evidence of disease. 4. Known or suspected history of Richter's transformation. 5. Known hypersensitivity to one or more study drugs. 6. Known bleeding disorders (eg, von Willebrand's disease or hemophilia). 7. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.

   8\. Known history of human immunodeficiency virus (HIV) or active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV). Subjects who are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result before enrolment. Those who are PCR positive will be excluded. 9. Unable to swallow capsules/tablets or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.

   10\. Concomitant use of warfarin or other vitamin K antagonists. 11. Major surgery within 4 weeks of first dose of study drug.

Where this trial is running

Milan, MI

• Strategic Research Program on CLL — Milan, MI, Italy (RECRUITING)

Study contacts

• Study coordinator: Paolo Ghia, MD, PhD

Conditions: Chronic Lymphocytic Leukemia