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Chronic Lymphocytic LeukemiaPhase 2ZFCR/ZBRNCT05287984

Zanubrutinib Followed Zanubrutinib Plus FCR / BR in Newly Diagnosed Symptomatic CLL/SLL

A Phase 2 study testing Zanubrutinib, Fludarabine, cyclophosphamide and rituximab and Zanubrutinib, bendamustine, rituximab in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Institute of Hematology & Blood Diseases Hospital, China 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 The sponsor has not verified this record for over two years, so it may be out of date.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 aims to evaluate the long-term efficacy of BTK inhibitor Zanubrutinib monotherapy , sequential Zanubrutinib combined (Fludarabine, cyclophosphamide and rituximab /bendamustine and rituximab)FCR/BR regimen by a limited period of treatment for the newly diagnosed Chronic Lymphocytic Leukemia (CLL) or Small… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Zanubrutinib, Fludarabine, cyclophosphamide and rituximab and Zanubrutinib, bendamustine, rituximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
63 participants
Where
1 siteChina
Study dates
22 Mar 2022to 29 Nov 2024
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 1. 18 Years and older (Adult, Older Adult)
  • 2. Age >65 years or age ≤65 years with creatinine clearance of 30-69 mL/min or patients with a cumulative Disease Rating Scale (CIRS-G) score greater than 6 point were enrolled in cohort 2 , other patients were enrolled in cohort 1.
  • 3. Confirmed diagnosis of CLL or SLL that meets the 2008 IWCLL criteria
  • 4. The patients are untreated or without prior systemic therapy for disease, the specific conditions are as follows:
  • a) Prior treatment with a fludarabine or treatment with bendamustine or rituximab regimen
  • b) Not treated with Chlorambucil, or treated with Chlorambucil for less than 4 weeks (alone or in combination with adrenal glucocorticoid)
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  • c) If the above treatment has been applied, it is necessary to stop treatment for 2 weeks before joining the group for treatment
  • 5. Treatment indications for CLL mainly include (meeting at least one of the following conditions):
  • a) Evidence of progressive bone marrow failure presenting as progressive decrease in hemoglobin and/or platelets
  • b) Splenomegaly (e.g., >6cm below the left costal margin) or progressive or symptomatic splenomegaly
  • c) giant lymph node enlargement (longest diameter >10cm) or progressive or symptomatic lymph node enlargement
  • d) Progressive lymphocytosis, such as lymphocytosis >50% within 2 months, or lymphocyte multiplication time (LDT) <6 months. When the initial lymphocyte was <30×109/L, LDT alone could not be used as a treatment indication
  • e) Autoimmune hemolytic anemia (AIHA) and/or immune thrombocytopenia (ITP) do not respond well to corticosteroids or other standard treatments
  • f) Symptoms associated with at least one of the following diseases: ①≥10% weight loss with no apparent cause in the previous 6 months; ② Severe fatigue (such as ECOG physical state ≥2 points; Unable to carry out regular activities); ③ No evidence of infection, body temperature >38℃, ≥2 weeks; (4) No evidence of infection, night sweats >1 month
  • 6. ECOG performance status of 0, 1, or 2
  • 7. The main organ functions met the following criteria within 7 days before treatment: Blood routine examination criteria: platelet ≥30×10^9/L; Biochemical tests should meet the following criteria: Total bilirubin (TBIL) ≤1.5 times the upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase AST≤2.5*ULN; Creatinine clearance rate ≥ 30mL /min; Cardiac Doppler ultrasonography: Left ventricular ejection fraction (LVEF)≥ the lower limit of normal (50%).
  • 8. Both men and women of reproductive age agreed to use reliable contraception throughout the study period and for up to four weeks after the end of treatment
  • 9. Life expectancy ≥ 6 months
  • 10. Patients voluntarily participated in the study and signed informed consent

Who cannot join

  • 1. Have been diagnosed or treated for malignancies other than CLL (including active CNS lymphoma) within the past year
  • 2. Clinical evidence suggests that Richter's transformation occurs
  • 3. Non-lymphoma-related liver and kidney function impairment: ALT > 3 times the upper limit of normal value, AST > 3 times the upper limit of normal value, TBIL > 2 times the upper limit of normal value, serum creatinine clearance <30ml/min
  • 4. Other serious medical conditions, such as uncontrolled diabetes, gastric ulcers, and other serious heart and lung diseases, may affect this study. The right to make judgments belongs to the researcher
  • 5. Diagnosed human immunodeficiency virus (HIV) infection or active hepatitis B virus (HBV) infection, or any uncontrolled active systemic infection requiring intravenous antibiotics.
  • (Note: Active HBV infection was defined as a.HBV DNA quantification ≥2000 IU/ mL; b. ALT≥2 times normal upper limit; c. To exclude hepatitis caused by other causes, such as the disease itself or drugs, the three conditions must be met simultaneously. Patients with active HBV infection at initial diagnosis and non-active HBV infection after anti-HBV treatment can be included in this study on the premise of adequate anti-HBV treatment.)
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  • 6. Clinical manifestations of central nervous dysfunction or CNS invasion
  • 7. Patients who have had major surgery (excluding lymph node biopsy) within the past 14 days or who are expected to require major surgery as part of their treatment
  • 8.Unable to swallow capsules or malabsorption syndrome, disease that significantly affects gastrointestinal function, previous gastrectomy or small bowel resection, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction
  • 9. Requires ongoing treatment with any medication which is a strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitor or strong CYP3A inducer
  • 10. Females who are currently pregnant or breastfeeding, or at a childbearing age who are not using contraception
  • 11. Clinically significant cardiovascular abnormalities (NYHA classification: III/IV) (Annex 3), patients with myocardial infarction, malignant arrhythmia (including QTC≥480ms), unsatisfactory blood pressure control with antihypertensive drugs (systolic blood pressure ≥150 mmHg, diastolic blood pressure ≥100 mmHg), and uncontrolled angina pectoris within 6 months before enrollment
  • 12. Persistent uncontrolled bleeding
  • 13. A history of life-threatening haemorrhage, especially from irreversible causes
  • 14. High doses of several anticoagulants are required and cannot be stopped for a short time
  • 15. evere allergy to the active ingredient or any excipients of the product

Trial locations and contacts

1 site in 1 country.

Shuhu Yi contact

86-22-23909106

yishuhua@ihcams.ac.cn

Lugui Qiu contact

86-22-23909172

qiulg@ihcams.ac.cn

China1 site

  • Institute of Hematology & Blood Diseases Hospital

    Tianjin, Tianjin Municipality, 300020

Other trials in China

About this study

Official title: A Phase 2 Clinical Trial to Evaluate the Efficacy of Zanubrutinib Followed Zanubrutinib Plus FCR (Fludarabine Cyclophosphamide and Rituximab) / BR(Bendamustine and Rituximab) in Newly Diagnosed Symptomatic CLL/SLL (STOP Trial)

This study aims to evaluate the long-term efficacy of BTK inhibitor Zanubrutinib monotherapy , sequential Zanubrutinib combined (Fludarabine, cyclophosphamide and rituximab /bendamustine and rituximab)FCR/BR regimen by a limited period of treatment for the newly diagnosed Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). The investigators propose this combination will improve the MRD negative rate of patients with CR/CRi after treatment was significantly higher than that of FCR chemotherapy can be a time-limited regimen which will reduce the life-time therapy and benefit the patients.

Read the detailed description

The investigators designed timed FCR/BR treatment for BTK inhibitor Zanubrutinib monotherapy after continuous remission, which shortened the treatment time, deepened the depth of remission, and enabled some patients to achieve deep remission (MRD negative), and realized long-term survival after drug withdrawal. Treatment regimens: Zanubrutinib monotherapy for 12 months followed by 4 courses of immunochemotherapy with FCR or BR. Cohort 1 was designed to apply FCR for patients aged 65 years or younger who could tolerate FCR. Cohort 2 was designed to apply BR in patients older than 65 years or unable to tolerate FCR.

Being tested
Zanubrutinib, Fludarabine, cyclophosphamide and rituximab, Zanubrutinib, bendamustine, rituximab
Keywords
chronic lymphocytic leukemia, Small Lymphocytic Lymphoma, newly diagnosed, Zanubrutinib
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.

  • Zanubrutinib, Fludarabine, cyclophosphamide and rituximabDrug

    Also called ZFCR regimen

    Patients aged 65 years or younger who can tolerate FCR.

  • Zanubrutinib, bendamustine, rituximabDrug

    Also called ZBR regimen

    For patients older than 65 years or who cannot tolerate FCR regimens.

Study groups in NCT05287984
Study groupRoleWhat they receive
ZFCR regimenExperimentalPatients aged 65 years or younger who can tolerate FCR： Patients in this group will receive zanubrutinib monotherapy for 12 months, then receive 4 cycles of zanubrutinib, fludarabine, cyclophosphamide and rituximab(ZFCR). Efficacy evaluation and MRD test of peripheral blood and bone marrow were performed at the 17th cycle after 16 cycles to obtain study end point data. Patients with CR/CRi and MRD negative could stop taking zanubrutinib, and other patients could stop taking zanubrutinib or continue treatment. Follow-up and efficacy assessment were conducted every three months.
Receives: Drug: Zanubrutinib, Fludarabine, cyclophosphamide and rituximab
ZBR regimenExperimentalFor patients older than 65 years or who cannot tolerate FCR regimens: Patients in this group will receive zanubrutinib monotherapy for 12 months, then receive 4 cycles of bendamostine and rituximab(BR). Efficacy evaluation and MRD test of peripheral blood and bone marrow were performed at the 17th cycle after 16 cycles to obtain study end point data. Patients with CR/CRi and MRD negative could stop taking zanubrutinib and other patients could stop taking zanubrutinib or continue treatment.
Receives: Drug: Zanubrutinib, bendamustine, rituximab

What is being measured

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

  1. MRD negative rate of CR patients

    The negative MRD rate of patients with CR at the end of 16 cycles of treatment

    Measured: up to the end of 16 cycles of treatment (each cycle is 28 days)

Secondary outcomes (8)

  1. overall response rate(ORR)

    Defined as the proportion of patients whose BICR was assessed for CR, CRi, or PR according to IWCLL 2018 criteria at or before initiation of subsequent antitumor therapy.

    Measured: up to the end of 16 cycles of treatment (each cycle is 28 days)

  2. Complete response (CR)

    Defined as the percentage of subjects who achieved CR after treatment in the conformance population and the intentionality treatment population.

    Measured: up to the end of 16 cycles of treatment (each cycle is 28 days)

  3. Duration of tumor remission(DOR)

    Defined as the time interval between the first documented remission of disease and the first documented evidence of PD for patients in the intentional-treatment population (ITT). Exit with no progress or no recorded time of disease progression, with the date of the last examination as the end date.

    Measured: up to 5 years

  4. time to next treatment(TTNT)

    Patients in the treatment-intentionality population (ITT) were defined from the beginning of first-line treatment to the beginning of back-line treatment or the time of death.

    Measured: up to 5 years

  5. Progress-free survival(PFS)

    the time from treatment initiation until disease progression or death, If there was no progress at the time of withdrawal or the time of disease progression was not recorded, the end date was the date of the last examination.

    Measured: up to 5 years

  6. The time at which the median MRD turned positive

    It was defined as the time for the median peripheral and/or bone marrow MRD to become positive in patients with CR/CRi and MRD negative in bone marrow and peripheral blood after the 16th cycle of treatment.

    Measured: up to 5 years

  7. overall survival

    Defined as the time interval from enrollment to death for patients in the treatment-intentionality population (ITT). If the patient remains alive or if it is not known whether the patient is alive or dead, the date of death will be adopted at the most recent point in time when the patient is known to be alive.

    Measured: up to 5 years

  8. Safety of treatment regimens

    Defined as treatment-related toxicity

    Measured: up to 5 years

Timeline

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

  1. First posted18 Mar 2022
  2. Study start22 Mar 2022 (estimated)
  3. Primary completion28 Jun 2024 (estimated)
  4. Study completion29 Nov 2024 (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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
63 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05287984
Sponsor's protocol ID
BDH-CLL-002-2022/02/14
Acronym
ZFCR/ZBR
Status last verified
Mar 2022
First submitted
26 Feb 2022
Last updated
31 Mar 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Davids MS, Brander DM, Kim HT, Tyekucheva S, Bsat J, Savell A, Hellman JM, Bazemore J, Francoeur K, Alencar A, Shune L, Omaira M, Jacobson CA, Armand P, Ng S, Crombie J, LaCasce AS, Arnason J, Hochberg EP, Takvorian RW, Abramson JS, Fisher DC, Brown JR; Blood Cancer Research Partnership of the Leukemia & Lymphoma Society. Ibrutinib plus fludarabine, cyclophosphamide, and rituximab as initial treatment for younger patients with chronic lymphocytic leukaemia: a single-arm, multicentre, phase 2 trial. Lancet Haematol. 2019 Aug;6(8):e419-e428. doi: 10.1016/S2352-3026(19)30104-8. Epub 2019 Jun 14.

    PubMed 31208944

  • Bottcher S, Ritgen M, Fischer K, Stilgenbauer S, Busch RM, Fingerle-Rowson G, Fink AM, Buhler A, Zenz T, Wenger MK, Mendila M, Wendtner CM, Eichhorst BF, Dohner H, Hallek MJ, Kneba M. Minimal residual disease quantification is an independent predictor of progression-free and overall survival in chronic lymphocytic leukemia: a multivariate analysis from the randomized GCLLSG CLL8 trial. J Clin Oncol. 2012 Mar 20;30(9):980-8. doi: 10.1200/JCO.2011.36.9348. Epub 2012 Feb 13.

    PubMed 22331940

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Zanubrutinib, Fludarabine, cyclophosphamide and rituximab and Zanubrutinib, bendamustine, rituximab in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Institute of Hematology & Blood Diseases Hospital, China 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 19 inclusion and 16 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 31 Mar 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 Shuhu Yi (86-22-23909106, yishuhua@ihcams.ac.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

MRD negative rate of CR patients (time frame: up to the end of 16 cycles of treatment (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 NCT05287984, which also lists 2 linked publications.

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 31 Mar 2022.

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