Orelabrutinib and Obinutuzumab Plus FC Regimen in Treating Newly Diagnosed CLL/SLL

  • End date
    Nov 5, 2025
  • participants needed
  • sponsor
    The First Affiliated Hospital with Nanjing Medical University
Updated on 1 May 2022


This study is a multi-center, open-label, single-arm, non-randomized phase II clinical study in order to evaluate the safety and efficacy of Orelabrutinib, Fludarabine, Cyclophosphamide, and Obinutuzumab (GA-101) (oFCG) in the Treatment of Newly Diagnosed Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)


Patients eligible for enrollment will receive 7-day lead-in therapy of orelabrutinib 150 mg once daily, followed by 3 cycles of orelabrutinib, fludarabine, cyclophosphamide, and obinutuzumab (oFCG) at 28-day intervals. After 3 cycles, bone marrow (BM) minimal residual disease (MRD) detection and efficacy evaluation (iwCLL2018 guidelines) are conducted. If BM MRD is negative (<10-4), patients will receive be treated with orelabrutinib plus obinutuzumab in 4-6 cycles; If BM MRD is positive (≥10-4), patients will receive the same regimen in 4-6 cycles as in previous 3 cycles. After 6 cycles of treatment, BM MRD detection and efficacy assessment will be conducted again. If BM MRD is negative (<10-4), orelabrutinib monotherapy will be administered in 7-12 cycles; If BM MRD is positive (≥10-4), treatment with orelabrutinib plus obinutuzumab will be administered in 7-12 cycles. After 12 cycles of treatment, BM MRD detection and efficacy evaluation will be performed. If BM MRD is negative (<10-4), orelabrutinib will be withdrawn and participants will turn to follow-up (efficacy assessment and MRD test will be performed according to the follow-up plan); if BM MRD is positive, treatment with orelabrutinib monotherapy will be administered in 13-24 cycles (continued even if BM MRD test was negative). After 24 cycles, if BM MRD is negative, the drug can be stopped and participants turn to follow-up. If BM MRD is positive, treatment can be continued until disease progression or be ceased by investigator due to no benefit from continued treatment, and BM MRD can be tested as planned. The trial is expected to end 36 months after enrollment of the last patient. If the subjects continue to require subsequent treatment with orelabrutinib, the sponsor will coordinate with the manufacturer and continue to provide the monotherapy treatment.

Condition Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Treatment cyclophosphamide, Fludarabine, Obinutuzumab, orelabrutinib
Clinical Study IdentifierNCT05322733
SponsorThe First Affiliated Hospital with Nanjing Medical University
Last Modified on1 May 2022


Yes No Not Sure

Inclusion Criteria

Age between 18 to 65 years old for both gender
Patients have a confirmed diagnosis of CD20-positive chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) and meet criteria to initiate first-line treatment per International Workshop on CLL Working Group (IWCLL) 2018 guidelines
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
At least one measurable disease detected by enhanced computerized tomography (CT) or magnetic resonance imaging (MRI). At least one lymph node with the longest axis >=1.5cm and one measurable vertical dimension
With life expectancy > 6 months
Patients must meet the following laboratory examination criteria during 14 days before
Serum bilirubin <1.5 Upper Limit of Normal (ULN), other than gilbert syndrome (defined as
unconjugated bilirubin>80%); Aspartate aminotransferase (AST) and alanine aminotransferase
(ALT) ≤2.5 ULN
Absolute neutrophil count (ANC)≥0.75×109/L and Platelets≥50×109/L (patients without
exposure to G-CSF or blood transfusion within 7 days and no exposure to )

Exclusion Criteria

Cumulative illness rating scale (CIRS) > 6
Creatinine clearance rate (Ccr) <70 ml/min calculated by Cockcroft-Gault formula or by
-hour urine analysis
Patients diagnosed as other malignancy except lymphoma, except patients with curative
intent and with no known active disease present for ≥ 5 years before the first dose of
study drug and felt to be at low risk for recurrence by treating physician
Patients with known central nervous system involvement
Patients with progressive multifocal leukoencephalopathy (PML)
Patients with history of Richter's Syndrome or suspected Richter's Syndrome
Uncontrolled autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura, e.g
persistent decreasing hemoglobin or platelet count requiring steroid therapy 4 weeks
before initiation of study
Prior exposure to systemic therapy for CLL/SLL (except for incomplete treatment
regimens fewer than 2 weeks such as antitumor steroid therapy)
Prior exposure to live vaccines, immunotherapy or other investigational therapeutic
agent within 4 weeks prior to enrollment
Requiring persistent steroid therapy for other non-antitumor purposes. Systemic
steroid drug use within 7 days of first dose of study drug except regional use of
steroid drug
Uncontrolled or other serious cardiovascular disease, including
New York Heart Association (NYHA) class II or higher congestive heart failure
unstable angina, myocardial infarction, or clinically significant arrhythmia
requiring medical intervention with a left ventricular ejection fraction (LVEF)
<50% at screening 6 months prior to initial administration of the study drug
Primary cardiomyopathy (such as dilated cardiomyopathy, hypertrophic
cardiomyopathy, rhythmogenesis right ventricular cardiomyopathy, restricted
cardiomyopathy, unshaped cardiomyopathy)
Clinically significant prolonged QTc interval, or QTc interval >470 ms in female
and >450 ms in male at screening
Uncontrolled hypertension: on the basis of lifestyle improvement, blood pressure
still fails to reach the standard after application of 2 or more kinds of
reasonable, tolerable and full dose antihypertensive drugs (including diuretics)
or 4 or more kinds of antihypertensive drugs until blood pressure can be
effectively controlled
Active bleeding within 2 months prior to screening, or taking anticoagulant/platelet
drugs, or have a definite bleeding tendency in the investigator's opinion (e.g
esophageal varices with bleeding risk, local active ulcer lesions)
History of stroke or intracranial hemorrhage within 6 months prior to enrollment
Clinically significant gastrointestinal abnormalities that may affect drug ingestion
transport, or absorption (e.g., inability to swallow, chronic diarrhea, intestinal
obstruction, etc.), or total gastrectomy
Major surgery within 4 weeks of first dose of study drug. Diagnostic examination is
not regarded as surgery and insertion of vascular access device excluded from the
Uncontrolled active systemic fungi, bacteria, virus (e.g. CMV DNA positive by PCR
analysis) or other infections (defined as showing persistent symptoms of infection and
no improvement although appropriate antibiotics or other treatment have been applied)
or requiring intravenous (IV) antibiotics administration
Known human immunodeficiency virus (HIV) infection, or active hepatitis B or C
infection (positive results from PCR analysis)
Known hypersensitivity to Orelabrutinib, Fludarabine, Cyclophosphamide or Obinutuzumab
Concurrent treatment with strong or moderate cytochrome P450, family 3, subfamily A
(CYP3A) inhibitors or inducers
Any mental or cognitive impairment that may limit their understanding of informed
consent and compliance with the study
Pregnant and lactating women, or women of childbearing age who are unwilling to use
contraception throughout the study period and within 18 months of the last
administration of obinutuzumab or within 180 days of the last administration of any
other study drug (women who were fertile must have a negative serological pregnancy
test within 14 days prior to initiation of study) Male without surgically sterilized
who are unwilling to use contraception throughout the study period and within 180 days
of the last administration of the study drug
Any life-threatening illness, medical condition, or organ system dysfunction that, in
the investigator's opinion, could compromise the subject's safety or put the study
outcomes at undue risk
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