Efficacy of First Line B-RI for Treatment Naive Waldenström's Macroglobulinemia

NCT03620903 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: ECWM-22017-004362-95
• Study Type: interventional
• Target: 53
• Locations: 2 countries
• Sites: 12

Brief Summary

In Waldenström 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. 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. Recent data confirmed high activity with low toxicity for ibrutinib in relapsed WM patients as single agent therapy. Based on these observations it is the aim of this study to investigate the efficacy and toxicity of the chemotherapy-free combination bortezomib, rituximab, ibrutinib (B-RI) in treatment naïve WM patient.

Conditions

Waldenstrom Macroglobulinemia

Keywords

Waldenstrom Macroglobulinemia, Ibrutinib, Bortezomib

Outcome Measures

Primary Outcomes (1)

• 1 year progression free survival

  The primary endpoint is the rate of 1 year progression free survival (1YPFS).

  1 year

Secondary Outcomes (10)

• Response rate

  6 months

• Best response

  up to 10 years

• Time to best response

  up to 10 years

• Time to first response

  up to 10 years

• Time to Treatment failure (TTF)

  up to 10 years

Study Arms (1)

Bortezomib-Rituximab-Ibrutinib

EXPERIMENTAL

Cycle 1: 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

Interventions

Ibrutinib / Bortezomib / Rituximab DRUG

Induction (Rituximab / Bortezomib / Ibrutinib), Maintenance I (Ibrutinib / Rituximab), Maintenance II (Ibrutinib)

Also known as: Imbruvica / Velcade / Mabthera

Bortezomib-Rituximab-Ibrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Presence of at least one criterion for initiation of therapy, according to the 2nd Workshop on WM:
• Recurrent fever, night sweats, weight loss, fatigue (at least one of them)
• Hyperviscosity
• Lymphadenopathy which is either symptomatic or bulky (≥5 cm in maximum diameter)
• Symptomatic hepatomegaly and/or splenomegaly
• Symptomatic organomegaly and/or organ or tissue infiltration
• Peripheral neuropathy due to WM
• Symptomatic cryoglobulinemia
• Cold agglutinin anemia
• Immunoglobulin M (IgM) related immune hemolytic anemia and/or thrombocytopenia
• Nephropathy related to WM
• Amyloidosis related to WM
• Hemoglobin ≤10g/dL
• Platelet count \<100x109/L
• Serum monoclonal protein \>5g/dL, even with no overt clinical symptoms

You may not qualify if:

• Prior systemic treatment of the WM (plasmapheresis and short - term administration of corticosteroids \< 4 weeks administered at a dose equivalent to \< 20 mg/day prednisone is allowed)
• Patient with hypersensitivity to Bortezomib
• Patient with hypersensitivity to MabThera
• Patient with hypersensitivity to Ibrutinib
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Uncontrolled viral infection
• Known history of human immunodeficiency virus (HIV) or active Hepatitis C Virus or active Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics.
• Congenital or acquired severe immunodeficiency not attributed to lymphoma (clinical appearance: recurrent infections, necessity of immunoglobulin substitution therapy, patients after transplantation)
• Known interstitial lung disease
• Prior allergic reaction or severe anaphylactic reaction related to humanized or murine monoclonal antibody.
• Central Nervous System involvement by lymphoma
• Prior history of malignancies unless the subject has been free of the disease for ≥ 5 years. Exceptions include the following:
• Basal cell carcinoma of the skin,
• Squamous cell carcinoma of the skin,
• Carcinoma in situ of the cervix,

Sponsors & Collaborators

• Christian Buske: lead
• University of Ulm: collaborator
• ClinAssess GmbH: collaborator
• Zentrum für Klinische Studien Ulm: collaborator
• Hoffmann-La Roche: collaborator
• Johnson & Johnson: collaborator

Study Sites (12)

Studiengesellschaft Onkologie Bielefeld GbR

Bielefeld, 33604, Germany

Location

DIAKO Ev. Diakonie-Krankenhaus gGmbH, Med. Klinik II

Bremen, 28239, Germany

Location

Universitätsklinikum Halle, Klinik für Innere Medizin IV

Halle, 06120, Germany

Location

Universtätsmedizin Mannheim, III. Medizinische Klinik Studienzentrale im MCC

Mannheim, 68167, Germany

Location

Kliniken Maria Hilf GmbH (Krankenhaus St. Franziskus), Medizinische Klinik I (Klinik f. Hämatologie, Onkologie, Gastroentereologie)

Mönchengladbach, 41063, Germany

Location

Kliniken Ostalb Stauferklinikum Schwäbisch Gmünd, Zentrum für Innere Medizin

Mutlangen, 73557, Germany

Location

Hämato-Onkologische Gemeinschaftspraxis Pasing-Fürstenfeldbruck

München, 81241, Germany

Location

Klinikum der Universität München, Medizinische Klinik und Poliklinik III

München, 83177, Germany

Location

Universitätsklinikum Münster, Med. Klinik A

Münster, 48149, Germany

Location

Universitätsklinikum Ulm; Klinik für Innere Medizin Innere Medizin III

Ulm, 89081, Germany

Location

Gemeinschaftspraxis Dres. Rudolf Schlag, Björn Schöttker, Joachim Haas

Würzburg, 97080, Germany

Location

'Alexandra' General Hospital of Athens

Athens, 11528, Greece

Location

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

ibrutinib; Bortezomib; Rituximab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Christian Buske, MD

  University of Ulm

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: August 2, 2018
• First Posted: August 8, 2018
• Study Start: September 11, 2019
• Primary Completion: November 14, 2022
• Study Completion (Estimated): February 1, 2027
• Last Updated: December 5, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (11); GR (1)