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Chronic Lymphocytic Leukemia/Small Lymphocytic LymphomaPhase 2NCT05322733

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

A Phase 2 study testing Orelabrutinib, Obinutuzumab and Fludarabine in people with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Orelabrutinib, Obinutuzumab and Fludarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteChina
Study dates
15 Apr 2022to 5 Nov 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 entry:
  • 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 )

Who cannot join

  • Cumulative illness rating scale (CIRS) > 6.
  • Creatinine clearance rate (Ccr) <70 ml/min calculated by Cockcroft-Gault formula or by 24-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.
Show all 26Show fewer
  • 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 criteria.
  • 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.

Trial locations and contacts

1 site in 1 country.

Jianyong Li, Phd, MD contact

025-83718836

lijianyonglm@126.com

China1 site, 1 recruiting

  • Department of Haematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital

    Nanjin, Jiangsu, 210029

    Huayuan Zhu, PhD，MD, 86 25 68306034, huayuan.zhu@hotmail.com

    Yeqin Sha, MD, yeqinsha@njmu.edu.cn

    Recruiting

Other trials in China

About this study

Official title: Efficacy and Safety of Orelabrutinib, Fludarabine, Cyclophosphamide, and Obinutuzumab (GA-101) (oFCG) in the Treatment of Newly Diagnosed Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)

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)

Read the detailed description

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.

Being tested
Orelabrutinib, Obinutuzumab, Fludarabine, Cyclophosphamide
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OrelabrutinibDrug

    Also called ICP-022

    150 mg capsules administered orally once daily (28-day cycles). Until 12 or 24 cycles and following BM undetectable MRD, or disease progression, or intolerant toxicity.

  • ObinutuzumabDrug

    Also called GA101

    1000 mg administered intravenously once on Day 1, 8, 15 of first cycle and on Day 1 of following cycles for maximal 12 cycles (28-day cycles).

  • FludarabineDrug

    Also called Fludara

    25mg/m2/day administered intravenously on Day 1-3 for every cycle (at most 6 cycles, 28-day cycles).

  • CyclophosphamideDrug

    250mg/m2/day administered intravenously on Day 1-3 for every cycle (at most 6 cycles, 28-day cycles).

Study groups in NCT05322733
Study groupRoleWhat they receive
Treatment (oFCG)ExperimentalSee Detailed Description.
Receives: Drug: Orelabrutinib; Drug: Obinutuzumab; Drug: Fludarabine; Drug: Cyclophosphamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. BM undetectable MRD rate after 6 cycles

    Participants who achieve bone marrow (BM) undetectable Minimal Residue Disease (uMRD) after 6 cycles detecting by four-color flow cytometry with a detection level of 10-4.

    Measured: at the end of 6 cycles(each cycle is 28 days)

Secondary outcomes (7)

  1. BM and PB undetectable MRD ratev after 3, 12, 24 cycles.

    participants who achieve BM uMRD (<10-4) on other important evaluation time-point (e.g. after 3, 12 and 24 cycles) except after 6 cycles. participants who achieve peripheral blood (PB) uMRD (<10-4) on important evaluation time-point.

    Measured: at the end of 3, 12, 24 cycles(each cycle is 28 days)

  2. Objective Response Rate (ORR)

    Response assessed after 3 and 6 cycles and up to approximately 3 years.

    Measured: at the end of 3, 6 cycles and up to approximately 3 years.(each cycle is 28 days)

  3. Complete Remission Rate (CRR)

    Response assessed after 3 and 6 cycles and up to approximately 3 years.

    Measured: at the end of 3, 6 cycles and up to approximately 3 years.(each cycle is 28 days)

  4. Duration of Response (DOR)

    DOR is defined as duration in days from the data of initial documentation of objective response to the date of first documented evidence of progressive disease (PD) or death from any cause. Response and PD are defined according to iwCLL 2018 guidelines.

    Measured: up to approximately 2, 3 years

  5. Progression Free Survival (PFS)

    PFS is defined as duration from the date of enrollment to date of progressive disease, replase, or death from any cause, whichever occurs first. PD are defined according to iwCLL 2018 guidelines.

    Measured: up to 3 years

  6. Overall Survival (OS)

    OS is defined as the time from the date of enrollment to the date of the participant's death from any cause.

    Measured: up to 3 years

  7. Incidence of adverse events (AEs)

    Treatment emergent adverse events (TEAE), severe adverse events (SAEs), adverse events of special interest (AESIs) and therapy-related AEs will be recorded and graded will be summarized by grade according to CTCAE (version 5.0).

    Measured: through study completion, an average of 4 year"

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Apr 2022
  2. Study start15 Apr 2022 (estimated)
  3. Primary completion22 Feb 2025 (estimated)
  4. Study completion5 Nov 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05322733
Sponsor's protocol ID
CWCLL-001
Status last verified
Apr 2022
First submitted
9 Mar 2022
Last updated
19 Apr 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Miao Y, Liu M, Qin S, Li F, Zhang J, Peng H, Ji C, Dai L, Zhou Z, Ding C, Wang Z, Sha Y, Qiu T, Tang H, Jin H, Fan L, Xu W, Li J, Xia Y, Zhu H. Orelabrutinib, fludarabine, cyclophosphamide, and obinutuzumab (OFCG) for first-line treatment of chronic lymphocytic leukemia: a multicenter phase II trial (cwCLL-001 trial). J Natl Cancer Cent. 2026 Apr 27;6(4):420-428. doi: 10.1016/j.jncc.2026.04.001. eCollection 2026 Aug.

    PubMed 42630801

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Orelabrutinib, Obinutuzumab and Fludarabine in people with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 19 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Jianyong Li, Phd, MD (025-83718836, lijianyonglm@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

BM undetectable MRD rate after 6 cycles (time frame: at the end of 6 cycles(each cycle is 28 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05322733, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2022.

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