Reply to S. Sarosiek et al.
Christian Buske, Meletios A Dimopoulos, Pierre Morel
https://pubmed.ncbi.nlm.nih.gov/37348018Actively Recruiting
Phase 2
Age: 18Years +
All Genders
ID05099471
Efficacy of Venetoclax Combined With Rituximab Compared to Chemotherapy Plus Rituximab in Treatment-Na efve Waldenstr f6m's Macroglobulinemia
Led by Christian Buske · Updated on 2026-05-05
80
Participants Needed
14
Research Sites
260 weeks
Total Duration
On this page
Sponsors
C
Christian Buske
Lead Sponsor
L
Ludwig-Maximilians - University of Munich
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are investigating treatment options for Waldenstr f6m's macroglobulinemia (WM), a condition where chemotherapy often results in low complete or very good partial response rates and limited duration of response. WM patients tend to be older and may not tolerate chemotherapy side effects well, so treatments without chemotherapy are especially appealing. Venetoclax, a drug approved for related blood cancers, has shown promising activity and low toxicity in WM patients, including those previously treated with Ibrutinib or with certain genetic mutations. Ibrutinib, while effective, requires continuous use and its success varies with genetic factors, limiting its adoption as a standard treatment. Fixed-duration treatment combining Venetoclax and Rituximab has shown deep responses in related diseases, suggesting it might improve outcomes for newly diagnosed WM patients. The study is an international, phase II, open-label, randomized trial comparing two treatment approaches for newly diagnosed WM patients needing therapy. One group receives a combination of Venetoclax and Rituximab, with Venetoclax dose gradually increased during the first 28-day cycle and continued for 12 cycles alongside Rituximab given intravenously monthly. The other group receives a combination of Dexamethasone, Rituximab, and Cyclophosphamide for six 28-day cycles. The study uses genetic markers MYD88 and CXCR4 to stratify patients before randomization. About 80 patients will participate across multiple sites. Participants will be monitored for treatment response and safety during and after therapy, with assessments including response rates at 12 and 24 months, progression-free survival over six years, and quality of life measured by questionnaires. Safety evaluations involve tracking adverse events, laboratory tests, heart monitoring, and vital signs over 12 months. The main goal is to see if Venetoclax plus Rituximab leads to better deep response rates compared to the standard chemotherapy combination. This trial aims to provide data supporting new treatment standards for WM.
CONDITIONS
Brief Title
Efficacy of Venetoclax in Combination With Rituximab in Waldenström's Macroglobulinemia
Who Can Participate
Age: 18Years +
All Genders
Eligibility Criteria
You may qualify if you...
- Proven diagnosis of Waldenstr�f6m's macroglobulinemia confirmed by pathology within the last 4 months
- De novo Waldenstr�f6m's macroglobulinemia regardless of genotype
- At least one symptom or clinical criterion requiring treatment, such as recurrent fever, night sweats, weight loss, fatigue, hyperviscosity, symptomatic organ enlargement, neuropathy, cryoglobulinemia, anemia, low platelet count due to lymphoma, or high serum monoclonal protein
- Age 18 years or older
- Life expectancy greater than 3 months
- ECOG performance status of 0 to 2
- Left ventricular ejection fraction of 40% or higher
- Adequate platelet and neutrophil counts unless due to bone marrow infiltration
- Adequate liver function (AST and ALT less than 3 times upper limit, bilirubin less than 1.5 times upper limit)
- Adequate kidney function with creatinine clearance of 30 mL/min or higher
- Women of childbearing potential must have a negative pregnancy test and agree to use effective birth control during and 12 months after therapy
- Men must agree to use birth control during and 12 months after therapy and not donate sperm
- Signed informed consent and adherence to study restrictions
- Affiliation to a social security scheme (for France only)
You will not qualify if you...
- Serious medical or psychiatric illness likely to interfere with study participation
- Known HIV infection
- Active severe infection or severe immunodeficiency not due to lymphoma
- Uncontrolled systemic infections or chronic hepatitis B or C requiring treatment
- Poor lung function (DLCO or FEV1 65% or less)
- Creatinine clearance between 30 and less than 45 mL/min
- Uncontrolled diabetes or hypertension
- Significant heart problems including heart failure, low ejection fraction (50% or less), unstable angina, recent heart attack, or serious arrhythmias
- New York Heart Association Class greater than 2
- Recent stroke or brain bleeding within 6 months
- Known pericardial disease or interstitial lung disease
- History of certain cancers unless disease-free for at least 3 years
- Known severe liver cirrhosis
- Recent chemotherapy or high-dose steroids
- Use of certain drugs that affect liver enzymes within 7 days before treatment
- Allergy to study drugs or required supportive medications
- Recent vaccination with live vaccines
- Pregnancy, breastfeeding without willingness to stop breastfeeding
- Participation in another clinical trial within 4 weeks
- No consent for data registration and processing
- Recent consumption of grapefruit, Seville oranges, or star fruit
- Inability to understand the clinical trial and provide informed consent
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
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Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Treatment
Duration - Up to 12 months
Participants receive either a combination of Venetoclax and Rituximab or a combination of Dexamethasone, Rituximab, and Cyclophosphamide according to their assigned treatment arm.
Monthly visits during treatment cycles
Follow-up
Duration - Up to 6 years
Participants are monitored for treatment response, safety, and long-term outcomes after the treatment period ends.
Periodic visits as scheduled for long-term monitoring
Trial Site Locations
Total: 14 locations
1
Onkologische Schwerpunktpraxis Bielefeld
Bielefeld, Germany, 33604
Actively Recruiting
2
Klinikum Chemnitz gGmbH
Chemnitz, Germany, 09116
Actively Recruiting
3
Klinikverbund Allgaeu gGmbH
Kempten, Germany, 87439
Actively Recruiting
4
Universitaetsklinikum Schleswig-Holstein AöR
Kiel, Germany, 24105
Actively Recruiting
5
Gemeinschaftsklinikum Mittelrhein gGmbH
Koblenz, Germany, 56073
Actively Recruiting
6
Dr. Vehling-Kaiser MVZ GmbH
Landshut, Germany, 84036
Actively Recruiting
7
Kliniken Maria Hilf GmbH Moenchengladbach
Mönchengladbach, Germany, 41063
Actively Recruiting
8
Kliniken Ostalb, Standort Stauferklinikum Schwäbisch Gmünd
Mutlangen, Germany, 73557
Not Yet Recruiting
9
Haematologie und Onkologie Muenchen-Pasing MVZ GmbH
München, Germany, 81241
Actively Recruiting
10
Universitaet Muenster
Münster, Germany, 48149
Actively Recruiting
11
Christliches Klinikum Paderborn, Brüderkrankenhaus St. Josef Paderborn
Paderborn, Germany, 33098
Actively Recruiting
12
Universitätsmedizin Rostock
Rostock, Germany, 18057
Not Yet Recruiting
13
University Hospital Ulm
Ulm, Germany, 89081
Actively Recruiting
14
Alexandra Hospital
Athens, Greece, 115 28
Actively Recruiting
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Research Team
D
Dajana Kaszynski, MSc
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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