Trial Title:
Zanubrutinib Plus BR in Newly Diagnosed Symptomatic WM
NCT ID:
NCT05914662
Condition:
Waldenstrom Macroglobulinemia
Conditions: Official terms:
Waldenstrom Macroglobulinemia
Rituximab
Bendamustine Hydrochloride
Zanubrutinib
Conditions: Keywords:
Waldenstrom macroglobulinemia
Zanubrutinib
newly diagnosed
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Patients were treated with ZBR regimen for 6 cycles, followed by Zanubrutinib monotherapy
for 6 months.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Zanubrutinib, Bendamustine and Rituximab
Description:
Zanubrutinib, 160mg orally, twice a day; Bendamustine 70 mg/m2 on days 1 and 2 of each
cycle; Rituximab (375 mg/m2 intravenously on day 0 of each cycle. ZBR was administered
every 4 weeks for a total of 6 cycles, followed by maintenance therapy with zanubrutinib
monotherapy for another 6 months.
Arm group label:
Zanubrutinib, bendamustine, rituximab combination therapy Group
Summary:
This study aims to evaluate the long-term efficacy of BTK inhibitor Zanubrutinib combined
bendamustine and rituximab (ZBR) for time-limited treatment of Waldenstrom
macroglobulinemia, The combination therapy is expected to improve the remission depth,
prolong the remission time, and improve the progression-free survival and overall
survival of newly diagnosed WM patients. On the one hand, the patients have to bear a
long-term economic burden, which is often difficult for some patients to adhere to for a
long time. On the other hand, in the course of long-term treatment of BTKi, drug
resistance and intolerable side effects are prone to occur. At the same time, it can
prevent the disease rebound after the withdrawal of BTKi, so as to achieve the phased
withdrawal of WM
Detailed description:
WM not only has the characteristics of lymphoma, such as lymphadenopathy,
hepatosplenomegaly, and tumor cells expressing CD20, but also has the characteristics of
myeloma, such as secreting monoclonal IgM, and tumor cells expressing plasma cell
differentiation marker CD38, etc. Clinical studies have also shown that BR regimen and
BTK inhibitor zanubrutinib are effective for WM.
This study aims to evaluate the long-term efficacy of BTK inhibitor Zanubrutinib combined
bendamustine and rituximab (ZBR) for time-limited treatment of Waldenstrom
macroglobulinemia, The combination therapy is expected to improve the remission depth,
prolong the remission time, and improve the progression-free survival and overall
survival of newly diagnosed WM patients. On the one hand, the patients have to bear a
long-term economic burden, which is often difficult for some patients to adhere to for a
long time. On the other hand, in the course of long-term treatment of BTKi, drug
resistance and intolerable side effects are prone to occur. At the same time, it can
prevent the disease rebound after the withdrawal of BTKi, so as to achieve the phased
withdrawal of WM. This prospective phase II study was designed to evaluate the rate of
deep response in newly diagnosed symptomatic WM. Eligible patients received ZBR for 6
cycles followed by zanubrutinib monotherapy for an additional 6 months.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- The gender of the patient is not limited, and the age is ≥18 years old;
- Must meet WM's diagnostic standards;
- The patient is an untreated or patient who has not undergone standard treatment.
- The specific conditions are as follows:
1. No combined chemotherapy with BTKi, BR, RCD, VRD, CHOP and COP
2. No treatment regimen containing fludarabine
3. Chlorambucil or cyclophosphamide for less than 4 weeks (alone or in combination
with adrenal glucocorticoids)
4. The above treatment did not reach the treatment response (MR)
5. If the above treatment has been applied, the treatment needs to be stopped for
2 weeks before entering the group to start treatment
- The indications for the treatment of indolent lymphoma mainly include (at least one
of the following conditions):
1. Symptomatic hyperviscosity;
2. Symptomatic peripheral neuropathy;
3. Amyloidosis;
4. Cold agglutinin disease; cryoglobulinemia;
5. Disease-related cytopenia (Hb<100 g/L, PLT<100×10^9/L);
6. Giant lymph nodes;
7. Those with systemic systemic symptoms: for two weeks/recurrent fever (above
38℃) and not caused by infection, or Night sweats and/or weight loss >10%
within 6 months;
8. The disease progresses rapidly, for example, the lymph nodes increase by more
than 50% within 2 months, and/or peripheral blood lymphocytes absolute value
doubling time <6 months, and/or rapid hemoglobin or platelet non-autoimmune
causes slow down
9. When there is evidence that the disease has transformed.
- ECOG score ≤ 2 points
- Laboratory examination: neutrophils ≥ 0.75×10^9/L; platelets ≥ 50×10^9/L; total
bilirubin ≤ 2.5 times upper limit; alanine aminotransferase/aspartate
aminotransferase ≤3 times upper limit. Creatinine clearance rate ≥ 30ml/min.
- The patient's expected survival time is ≥ 3 months.
Exclusion Criteria:
- Malignant tumors (including active central nervous system lymphoma) other than B-NHL
have been diagnosed or treated within the past year;
- There is clinical evidence that large cell lymphoma transformation has occurred;
- Non-lymphoma-related liver and kidney damage: alanine aminotransferase (ALT)> 3
times the upper limit of normal value, aspartate aminotransferase (AST)> 3 times the
upper limit of normal value, total bilirubin (TBIL)> upper limit of normal value 2
Times, serum creatinine clearance rate <30ml/min;
- Other serious medical conditions will affect the study (such as uncontrolled
diabetes, gastric ulcers, other serious cardiopulmonary diseases, etc.). The
decision-making power belongs to the researcher;
- Known history of infection with human immunodeficiency virus (HIV) or active
hepatitis B virus (HBV) infection, or any uncontrolled active systemic infection
requiring intravenous antibiotics.
- Central nervous system dysfunction with clinical manifestations or central invasion
(Bing-Neel syndrome);
- Patients who have undergone major surgery (not including lymph node biopsy) within
the past 14 days or expected major surgery during treatment;
- Inability to swallow capsules or suffer from malabsorption syndrome, diseases that
significantly affect gastrointestinal function, have undergone gastric or small
bowel resection, symptomatic inflammatory bowel disease or ulcerative colitis,
partial or complete intestinal obstruction.
- Need to receive strong cytochrome P450 (CYP) 3A inhibitor treatment.
- Women who are pregnant or breastfeeding, women of childbearing age who have not
taken contraception;
- Allergy to the drugs used.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Institute of Hematology & Blood Diseases Hospital
Address:
City:
Tianjin
Zip:
300020
Country:
China
Status:
Recruiting
Contact:
Last name:
Shuhua Yi, Dr.
Phone:
86-22-23909106
Email:
yishuhua@ihcams.ac.cn
Contact backup:
Last name:
Lugui Qiu, Dr.
Phone:
86-22-23909172
Email:
qiulg@ihcams.ac.cn
Start date:
February 15, 2023
Completion date:
December 15, 2025
Lead sponsor:
Agency:
Institute of Hematology & Blood Diseases Hospital, China
Agency class:
Other
Source:
Institute of Hematology & Blood Diseases Hospital, China
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05914662
