Back to resultsFixed-duration Therapy With Ibrutinib and Obinutuzumab (GA-101) in Treatment-naïve Patients With CLL (FIGHT)
Primary Purpose
Chronic Lymphocytic Leukemia
Status
Recruiting
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Ibrutinib and obinutuzumab
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Lymphocytic Leukemia
Eligibility Criteria
Inclusion Criteria:
- Age ≥18 years
- Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that meets iwCLL diagnostic criteria
- Previously untreated active disease requiring treatment per iwCLL criteria
- ECOG PS 0 or 1
- Measurable lymph node disease (>1.5 cm longest diameter) by CT scan
Adequate hematologic function defined as:
- Absolute neutrophil count (ANC) >750 cells/μL (750 cells/mm3 or 0.75 x 109/L)
- Platelet count >30,000/μL (30,000 cells/mm3 or 30 x 109/L)
- Hemoglobin >8.0 g/dL
Adequate hepatic and renal function defined as:
- Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤3.0 x upper limit of normal (ULN)
- Estimated Creatinine Clearance (CrCl) ≥30 mL/min (Cockcroft- Gault)
- Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
- 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:
- 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
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
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.
Sites / Locations
- Strategic Research Program on CLLRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Ibrutinib + obinutuzumab
Arm Description
Ibrutinib 420 mg QD for 24 months (Cycles 1-24) Obinutuzumab starting from Cycle 13 Day 1 (100 mg Cycle 13 Day 1, 900 mg Cycle 13 Day 2, 1000 mg Cycle 13 Days 8 and 15, 1000 mg Cycles 14-18 Day 1).
Outcomes
Primary Outcome Measures
BM MRD <10-4 at 30 days follow-up
To evaluate the rate of bone marrow minimal residual disease <10-4 at +30 Days follow-up after ibrutinib and obinutuzumab
Secondary Outcome Measures
Overall response rate at 30 days follow-up
To evaluate response to treatment after ibrutinib and obinutuzumab
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04908228
Brief Title
Fixed-duration Therapy With Ibrutinib and Obinutuzumab (GA-101) in Treatment-naïve Patients With CLL
Acronym
FIGHT
Official Title
Fixed-duration Therapy With Ibrutinib and Obinutuzumab (GA-101) in Treatment-naïve Patients With CLL
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 13, 2021 (Actual)
Primary Completion Date
September 15, 2026 (Anticipated)
Study Completion Date
September 15, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Paolo Ghia
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a phase 2 multicenter national interventional pharmacological study aimed at determining the efficacy of a fixed duration treatment with ibrutinib and obinutuzumab in terms of uMRD in the BM at the end of treatment (+30 Days follow-up).
Treatment with ibrutinib and obinutuzumab will be administered according to the following schedule:
Ibrutinib 420 mg QD for 24 months (Cycles 1-24) Obinutuzumab starting from Cycle 13 Day 1 (100 mg Cycle 13 Day 1, 900 mg Cycle 13 Day 2, 1000 mg Cycle 13 Days 8 and 15, 1000 mg Cycles 14-18 Day 1).
At the end of Cycle 24 all responding patients will discontinue ibrutinib and proceed with follow-up. If disease relapse occurs at any time after discontinuing treatment, ibrutinib therapy will be reintroduced at the standard dose of 420 mg QD and response to treatment monitored over time. Patients with stable (SD) or progressive disease (PD) at the end of Cycle 24, will continue ibrutinib as long as the treating physician deems they are benefiting from treatment and will be followed up in the study for survival and response to subsequent therapies.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
53 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Ibrutinib + obinutuzumab
Arm Type
Experimental
Arm Description
Ibrutinib 420 mg QD for 24 months (Cycles 1-24) Obinutuzumab starting from Cycle 13 Day 1 (100 mg Cycle 13 Day 1, 900 mg Cycle 13 Day 2, 1000 mg Cycle 13 Days 8 and 15, 1000 mg Cycles 14-18 Day 1).
Intervention Type
Drug
Intervention Name(s)
Ibrutinib and obinutuzumab
Other Intervention Name(s)
Imbruvica and Gazyvaro
Intervention Description
Patients will receive fixed-duration treatment with ibrutinib and obinutuzumab.
Primary Outcome Measure Information:
Title
BM MRD <10-4 at 30 days follow-up
Description
To evaluate the rate of bone marrow minimal residual disease <10-4 at +30 Days follow-up after ibrutinib and obinutuzumab
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Overall response rate at 30 days follow-up
Description
To evaluate response to treatment after ibrutinib and obinutuzumab
Time Frame
24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥18 years
Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that meets iwCLL diagnostic criteria
Previously untreated active disease requiring treatment per iwCLL criteria
ECOG PS 0 or 1
Measurable lymph node disease (>1.5 cm longest diameter) by CT scan
Adequate hematologic function defined as:
Absolute neutrophil count (ANC) >750 cells/μL (750 cells/mm3 or 0.75 x 109/L)
Platelet count >30,000/μL (30,000 cells/mm3 or 30 x 109/L)
Hemoglobin >8.0 g/dL
Adequate hepatic and renal function defined as:
Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤3.0 x upper limit of normal (ULN)
Estimated Creatinine Clearance (CrCl) ≥30 mL/min (Cockcroft- Gault)
Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
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:
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
Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Paolo Ghia, MD, PhD
Phone
+39022643
Ext
4797
Email
ghia.paolo@hsr.it
First Name & Middle Initial & Last Name or Official Title & Degree
Eloise Scarano, PhD
Phone
+39022643
Ext
3919
Email
scarano.eloise@hsr.it
Facility Information:
Facility Name
Strategic Research Program on CLL
City
Milano
State/Province
MI
ZIP/Postal Code
20132
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paolo Ghia, MD PhD
Phone
+39022643
Ext
3919
Email
scarano.eloise@hsr.it
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Fixed-duration Therapy With Ibrutinib and Obinutuzumab (GA-101) in Treatment-naïve Patients With CLL
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