Efficacy of First Line DRC +/- Bortezomib for Patients With Waldenström's Macroglobulinemia
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ClinicalTrials.gov Identifier: NCT01788020 |
Recruitment Status :
Completed
First Posted : February 11, 2013
Last Update Posted : May 13, 2024
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Tracking Information | ||||||||||||||||||||||||||||||||||
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First Submitted Date ICMJE | February 1, 2013 | |||||||||||||||||||||||||||||||||
First Posted Date ICMJE | February 11, 2013 | |||||||||||||||||||||||||||||||||
Last Update Posted Date | May 13, 2024 | |||||||||||||||||||||||||||||||||
Study Start Date ICMJE | November 2013 | |||||||||||||||||||||||||||||||||
Actual Primary Completion Date | November 2018 (Final data collection date for primary outcome measure) | |||||||||||||||||||||||||||||||||
Current Primary Outcome Measures ICMJE |
Progression Free Survival [ Time Frame: participants will be followed for their participation in the trial, an expected average of 5.5 years ] PFS will be calculated from the date of inclusion/randomisation to the following events: the date of progression and the date of death if it occurred earlier. In the absence of progression and death, PFS duration will be censored at the stopping date or the date of last follow-up.
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Original Primary Outcome Measures ICMJE |
Progression Free Survival [ Time Frame: participants will be followed for their participation in the trial, an expected average of 5.5 years ] PFS will be calculated from the date of inclusion to the stopping date or the date of progression, the date of last follow-up or the date of death if they occurred earlier.
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Change History | ||||||||||||||||||||||||||||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | |||||||||||||||||||||||||||||||||
Original Other Pre-specified Outcome Measures | Not Provided | |||||||||||||||||||||||||||||||||
Descriptive Information | ||||||||||||||||||||||||||||||||||
Brief Title ICMJE | Efficacy of First Line DRC +/- Bortezomib for Patients With Waldenström's Macroglobulinemia | |||||||||||||||||||||||||||||||||
Official Title ICMJE | Efficacy of First Line Dexamethasone, Rituximab and Cyclophosphamide (DRC) +/- Bortezomib for Patients With Waldenström's Macroglobulinemia | |||||||||||||||||||||||||||||||||
Brief Summary | In Waldenström macroglobulinemia (WM) conventional chemotherapy induces only low CR rates and responses of short duration compared to other indolent lymphomas. Thus innovative approaches are needed which combine excellent activity and tolerability in patients with WM, who are mostly of advanced age. The immunochemotherapy DRC (dexamethasone, rituximab, cyclophosphamide) was shown to be highly effective in patients with WM without inducing major hematological toxicities. On the other hand the proteasome inhibitor Bortezomib showed substantial activity as a single agent in WM with only very few side effects when given in a weekly schedule. Based on these observations it is the aim of this study to test whether the efficacy of the well tolerated DRC regime can be further improved by adding Bortezomib. | |||||||||||||||||||||||||||||||||
Detailed Description | Waldenström's macroglobulinemia (WM) is defined by a bone marrow infiltration by lymphoplasmacytic cells and the presence of a monoclonal immunoglobulin (Ig) M gammopathy in the peripheral blood. The clinical understanding of the disease has been greatly improved by the identification of internationally recognized criteria for initiating therapy, the description of an international prognostic index for patients requiring a first-line therapy and the definition of response criteria. These criteria are mainly based on the evolution of serum IgM concentration. However, delayed IgM monoclonal protein responses may cause important difficulties in response assessment. In addition, discrepancies between the kinetics of serum M protein reduction and the clearance of monoclonal B-cells from the bone marrow have been reported. Despite continuing advances in the therapy of WM, the disease remains incurable with a median survival of 5 to 8 years from the time of diagnosis thereby necessitating the development and evaluation of novel treatment approaches. | |||||||||||||||||||||||||||||||||
Study Type ICMJE | Interventional | |||||||||||||||||||||||||||||||||
Study Phase ICMJE | Phase 3 | |||||||||||||||||||||||||||||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE | Waldenström's Macroglobulinemia | |||||||||||||||||||||||||||||||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Buske C, Dimopoulos MA, Grunenberg A, Kastritis E, Tomowiak C, Mahe B, Troussard X, Hajek R, Viardot A, Tournilhac O, Aurran T, Lepretre S, Zerazhi H, Hivert B, Leblond V, de Guibert S, Brandefors L, Garcia-Sanz R, Gomes da Silva M, Kimby E, Schmelzle B, Kaszynski D, Dreyhaupt J, Muche R, Morel P. Bortezomib-Dexamethasone, Rituximab, and Cyclophosphamide as First-Line Treatment for Waldenstrom's Macroglobulinemia: A Prospectively Randomized Trial of the European Consortium for Waldenstrom's Macroglobulinemia. J Clin Oncol. 2023 May 10;41(14):2607-2616. doi: 10.1200/JCO.22.01805. Epub 2023 Feb 10. | |||||||||||||||||||||||||||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||||||||||||||||||||||||||||||||
Recruitment Status ICMJE | Completed | |||||||||||||||||||||||||||||||||
Actual Enrollment ICMJE |
202 | |||||||||||||||||||||||||||||||||
Original Estimated Enrollment ICMJE |
380 | |||||||||||||||||||||||||||||||||
Actual Study Completion Date ICMJE | April 2024 | |||||||||||||||||||||||||||||||||
Actual Primary Completion Date | November 2018 (Final data collection date for primary outcome measure) | |||||||||||||||||||||||||||||||||
Eligibility Criteria ICMJE | Inclusion Criteria: Clinicopathological diagnosis of WM as defined by consensus panel one of the Second International Workshop on WM. Pathological diagnosis has to occur before study inclusion and randomization. In addition, pathological specimens have to be sent to the national pathological reference center at study inclusion and randomization. The positivity for CD20 can be assumed from any previous bone marrow immunohistochemistry or flow cytometry analysis performed up to 6 months prior to enrollment. Inclusion in the study will be based on morphological and immunological criteria. Immunophenotyping will be performed in each center and saved locally. Flow cytometry of bone marrow and blood cells will include at least one double staining and assess the expression of the following antigens: surface immunoglobulin, CD19, CD20, CD5, CD10 and CD23. Patients are eligible if tumor cells express the following antigens: CD19, CD20, and if they are negative for CD5, CD10 and CD23 expression. Patients with tumor cells positive for CD5 and/or CD23 and morphologically similar to WM cells may be included after ruling out other low grade B-cell malignancies.
Exclusion criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | |||||||||||||||||||||||||||||||||
Accepts Healthy Volunteers ICMJE | No | |||||||||||||||||||||||||||||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||||||||||||||||||||||||||||||||
Listed Location Countries ICMJE | Germany | |||||||||||||||||||||||||||||||||
Removed Location Countries | ||||||||||||||||||||||||||||||||||
Administrative Information | ||||||||||||||||||||||||||||||||||
NCT Number ICMJE | NCT01788020 | |||||||||||||||||||||||||||||||||
Other Study ID Numbers ICMJE | ECWM-1 2013-000506-37 ( EudraCT Number ) |
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Has Data Monitoring Committee | Yes | |||||||||||||||||||||||||||||||||
U.S. FDA-regulated Product | Not Provided | |||||||||||||||||||||||||||||||||
IPD Sharing Statement ICMJE | Not Provided | |||||||||||||||||||||||||||||||||
Current Responsible Party | Christian Buske, University of Ulm | |||||||||||||||||||||||||||||||||
Original Responsible Party | Same as current | |||||||||||||||||||||||||||||||||
Current Study Sponsor ICMJE | University of Ulm | |||||||||||||||||||||||||||||||||
Original Study Sponsor ICMJE | Same as current | |||||||||||||||||||||||||||||||||
Collaborators ICMJE | Centre Hospitalier de Lens (Co-Sponsor) | |||||||||||||||||||||||||||||||||
Investigators ICMJE |
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PRS Account | University of Ulm | |||||||||||||||||||||||||||||||||
Verification Date | May 2024 | |||||||||||||||||||||||||||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |