A Prospective Cohort of Obinutuzumab and Chlorambucil (GC) Chemotherapy for the Treatment of Elderly Patients With Chronic Lymphocytic Leukemia Including Next- Generation Sequencing (NGS)-Based Assessment

Study Overview
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Brief Summary
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This study is prospective, open-label, single arm observational study to assess efficacy of obinutuzumab plus chlorambucil (GC) chemotherapy in treatment naïve CLL, and prognostic impact of genetic alterations for CLL using NGS.

Official Title
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A Prospective Cohort of Obinutuzumab and Chlorambucil (GC) Chemotherapy for the Treatment of Elderly Patients With Chronic Lymphocytic Leukemia Including Next- Generation Sequencing (NGS)-Based Assessment

Conditions
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Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: Obinutuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible subjects will be considered for inclusion in this study if they meet all of the following criteria: Newly diagnosed chronic lymphocytic leukemia Age≥ 70 years Satisfy the one of indications for starting treatment guideline Evidence of progressive marrow failure (anemia, thrombocytopenia) AIHA, thrombocytopenia refractory to steroids Massive (>6cm, LCM) or symptomatic splenomegaly Massive nodes (>10 cm) or symptomatic Progressive lymphocytosis 50% increase over 2 months or LDT < 6 months Constitutional Symptoms : weight loss > 10% in 6 months, significant fatigue, fever >38 over 2 weeks, night sweat > 1month 4. ECOG performance status 0-2 5. Total bilirubin ≤ 1.5 x ULN (upper limit of normal) 6. Aspartate aminotransferase (AST) ≤ 5 x ULN, (ALT) ≤ 5 x ULN 7. Creatinine ≤ 3.0 x ULN 8. Provide informed consent Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information Exclusion Criteria: Unmet NGS samples by bone marrow biopsy or peripheral bloods at diagnosis Hairy cell leukemia or prolymphocytic leukemia Uncontrolled infection Therapy history with combined chemotherapy or biologic therapy prior to registration History of thromboembolic episodes ≤ 3 months prior to registration Active hepatitis B or C with uncontrolled disease Active other malignancy requiring treatment that would interfere with the assessments of response of the lymphoma to protocol treatment Any severe and/or uncontrolled medical conditions or other conditions that could adversely impact their ability to participate in the study Concurrent participation in another therapeutic clinical trial.

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GC chemotherapy<br>Before administration of GC chemotherapy, all patients must undergo pretreatment bone marrow biopsy. The pretreatment BM biopsy must include at least 1 long core biopsy samples and 10 cc of aspirate. Obinutuzumab 1000mg fixed dose will be administered intravenously (Day 1,8,15 for cycle 1 and D1 for subsequent cycles). Chlorambucil 0.5mg/kg will be administered orally (D1,15 for all cycles). 28 days are considered as one cycle, and cycles will be repeated every 4-weeks for a total of 6 cycles. | Drug: Obinutuzumab<br>* Obinutuzumab is provided as single-use vials for intravenous administration only. Obinutuzumab 1000mg fixed dose will be administered Chlorambucil would be provided as oral tablet with dose of 0.5mg/kg Day 1 to day 28 is considered one cycle, and cycles will be repeated every 4-weeks, until 6 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | iwCLL criteria | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission rate | No evidence of disease at the time of tumor assessment by NGS method | 3 years | 
| Progression free survival | the time from first dose to documented disease progression | 3 years | 
| Overall survival | the time from first dose to death from any cause | 3 years |