Efficacy of First Line B-RI for Treatment Naive Waldenström's Macroglobulinemia
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03620903|
Recruitment Status : Active, not recruiting
First Posted : August 8, 2018
Last Update Posted : March 8, 2022
|Condition or disease||Intervention/treatment||Phase|
|Waldenstrom Macroglobulinemia||Drug: Ibrutinib / Bortezomib / Rituximab||Phase 2|
In Waldenström's macroglobulinemia (WM) conventional chemotherapy induces only low complete remission (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. Today, chemotherapy in combination with the anti-cluster of differentiation (CD) 20 antibody rituximab is still the backbone of treatment in patients with WM and is recommended as first line in national and international treatment guidelines. With the approval of Ibrutinib by the European Medicines Agency (EMA) 2015 for patients with relapsed WM or for patients not eligible for chemotherapy with treatment naïve WM treatment landscape has changed in this lymphoma subtype and there is an urgent need to evaluate to which extent chemotherapy-free approaches add clinical benefit to the patient. The treatment in the "European Consortium for Waldenström's Macroglobulinemia" (ECWM)-2 trial will test, whether the chemotherapy-free approach, which is given orally (ibrutinib) and subcutaneously (bortezomib and rituximab from cycle 2 onwards) (B-RI) will approach the efficacy of chemotherapy containing treatment concepts, but avoids chemotherapy associated toxicity. From the perspective of single agent ibrutinib, this regimen tests whether ibrutinib can be further optimized by adding rituximab and bortezomib. The combination of rituximab and ibrutinib was tested in comparison to rituximab/placebo in a large international phase III trial on behalf of the European Consortium for Waldenström's Macroglobulinemia in relapsed and first line WM, and results were recently published: in this trial no unexpected toxicity of the combination ibrutinib/rituximab was reported. Furthermore, ibrutinib/rituximab was significantly superior to rituximab/placebo with regard to response rates and PFS. From the perspective of the established rituximab/bortezomib regimen, the combination of B-RI will evaluate whether adding ibrutinib to this combination will add any benefit for the patient.
To this end, the aim of the study is to assess the toxicity and efficacy of B-RI in an exploratory phase II trial.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||53 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Efficacy of First Line Bortezomib, Rituximab, Ibrutinib (B-RI) for Patients With Treatment Naive Waldenström's Macroglobulinemia|
|Actual Study Start Date :||September 11, 2019|
|Estimated Primary Completion Date :||December 2022|
|Estimated Study Completion Date :||September 2029|
Rituximab: 375 mg/m2 intravenously (i.v) day 1; Bortezomib:1.6 mg/ m2 subcutanously (SC) day 1,8,15; Ibrutinib: 420 mg orally (p.o.) day 1-28;
Cycle 2-6 Rituximab: 1400 mg absolute SC day 1; Bortezomib:1.6 mg/ m2 SC day 1,8,15; Ibrutinib: 420 mg p.o. day 1-28;
Maintenance I (1 cycle = 56 days):
Ibrutinib 420 mg p.o. daily, until evidence of progressive disease or no longer tolerated by the subject (for a maximum of 10 years); Rituximab 1400 mg absolute SC day 1, every second month for 24 months (month 7-30);
Maintenance II (1 cycle = 84 days):
Ibrutinib 420 mg p.o. daily, until evidence of progressive disease or no longer tolerated by the subject (for a maximum of 10 years);
Drug: Ibrutinib / Bortezomib / Rituximab
Induction (Rituximab / Bortezomib / Ibrutinib), Maintenance I (Ibrutinib / Rituximab), Maintenance II (Ibrutinib)
Other Name: Imbruvica / Velcade / Mabthera
- 1 year progression free survival [ Time Frame: 1 year ]The primary endpoint is the rate of 1 year progression free survival (1YPFS).
- Response rate [ Time Frame: 6 months ]response rates (CR, VGPR, PR, MR) and overall response rate (CR, VGPR, PR, MR)
- Best response [ Time Frame: up to 10 years ]At least achieving a MR
- Time to best response [ Time Frame: up to 10 years ]time from the start of induction to best response the patient achieves (CR, VGPR, PR, MR).
- Time to first response [ Time Frame: up to 10 years ]time from the start of induction to first response (MR, PR, VGPR or CR).
- Time to Treatment failure (TTF) [ Time Frame: up to 10 years ]time of start of induction treatment to discontinuation of therapy for any reason including death from any cause, progression, toxicity or add-on of new anti-cancer therapy.
- Remission duration (RD) [ Time Frame: up to 10 years ]patients with response (CR, VGPR, PR, MR) from the date of response to the date of progression, relapse or death from any cause.
- Progression Free Survival (PFS) [ Time Frame: up to 10 years ]date of start of treatment to the following events: the date of progression and the date of death if it occurred earlier.
- Cause specific survival (CSS) [ Time Frame: up to 10 years ]period from the start of induction treatment to death from lymphoma or lymphoma related cause
- Overall survival (OS) [ Time Frame: up to 10 years ]period from the start of induction treatment to death from any cause.
- Safety Analysis [ Time Frame: up to 10 years ]Safety including treatment associated adverse events.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03620903
|Helios Klinikum Berlin-Buch, Klinik für Hämatologie und Stammzelltransplantation|
|Berlin, Germany, 13125|
|Studiengesellschaft Onkologie Bielefeld GbR|
|Bielefeld, Germany, 33604|
|DIAKO Ev. Diakonie-Krankenhaus gGmbH, Med. Klinik II|
|Bremen, Germany, 28239|
|Universitätsklinikum Halle, Klinik für Innere Medizin IV|
|Halle, Germany, 06120|
|Gemeinschaftspraxis, FÄ f. innere Medizin Hämatologie/Onkologie|
|Magdeburg, Germany, 39104|
|Universtätsmedizin Mannheim, III. Medizinische Klinik Studienzentrale im MCC|
|Mannheim, Germany, 68167|
|Kliniken Ostalb Stauferklinikum Schwäbisch Gmünd, Zentrum für Innere Medizin|
|Mutlangen, Germany, 73557|
|Kliniken Maria Hilf GmbH (Krankenhaus St. Franziskus), Medizinische Klinik I (Klinik f. Hämatologie, Onkologie, Gastroentereologie)|
|Mönchengladbach, Germany, 41063|
|Hämato-Onkologische Gemeinschaftspraxis Pasing-Fürstenfeldbruck|
|München, Germany, 81241|
|Klinikum der Universität München, Medizinische Klinik und Poliklinik III|
|München, Germany, 83177|
|Universitätsklinikum Münster, Med. Klinik A|
|Münster, Germany, 48149|
|SHR Kliniken Landkreis Sigmaringen GmbH, Hämatologie u. Internistische Onkologie|
|Sigmaringen, Germany, 72488|
|Universitätsklinikum Ulm; Klinik für Innere Medizin Innere Medizin III|
|Ulm, Germany, 89081|
|Gemeinschaftspraxis Dres. Rudolf Schlag, Björn Schöttker, Joachim Haas|
|Würzburg, Germany, 97080|
|'Alexandra' General Hospital of Athens|
|Athens, Greece, 11528|
|Principal Investigator:||Christian Buske, MD||University of Ulm|