Efficacy of First Line DRC +/- Bortezomib for Patients With Waldenström's Macroglobulinemia

NCT01788020 | Completed Phase 3 DMC

• 2 other identifiers: ECWM-12013-000506-37
• Study Type: interventional
• Target: 202
• Locations: 1 country
• Sites: 1

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.

Conditions

Waldenström's Macroglobulinemia

Keywords

DRC; Bortezomib; Oncology

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  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.

  participants will be followed for their participation in the trial, an expected average of 5.5 years

Secondary Outcomes (8)

• Response rate

  24 weeks

• Best response

  24 weeks

• Time to best response

  24 weeks

• Time to first response

  24 weeks

• Time to treatment failure

  participants will be followed for their participation in the trial, an expected average of 5.5 years

Study Arms (2)

DRC+Bortezomib

EXPERIMENTAL

Induction experimental arm (Arm B): Cycle 1: Bortezomib 1.6 mg/m2 s.c. Day 1,8,15; Dexamethasone 20 mg p.o. Day 1; Rituximab 375 mg/m2 i.v. Day 1; Cyclophosphamide 100 mg/m2 x 2 p.o. Day 1-5 Cycle 2-6: Bortezomib 1.6 mg/m2 s.c. Day 1,8,15; Dexamethasone 20 mg p.o. Day 1; Rituximab 1400 mg absolute sc Day 1; Cyclophosphamide 100 mg/m2 x 2 p.o. Day 1-5; Repeat day 29.

Drug: Dexamethasone, Rituximab, Cyclophosphamide, Bortezomib

DRC

ACTIVE COMPARATOR

Induction standard arm (Arm A) Cycle 1: Dexamethasone 20 mg p.o. Day 1; Rituximab 375 mg/m2 i.v. Day 1; Cyclophosphamide 100 mg/m2 x 2 p.o. Day 1-5; Cycle 2-6: Dexamethasone 20 mg p.o. Day 1; Rituximab 1400 mg absolute sc Day 1; Cyclophosphamide 100 mg/m2 x 2 p.o. Day 1-5; Repeat day 29.

Drug: Dexamethasone, Rituximab, Cyclophosphamide

Interventions

Dexamethasone, Rituximab, Cyclophosphamide DRUG

DRC

Dexamethasone, Rituximab, Cyclophosphamide, Bortezomib DRUG

DRC+Bortezomib

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
• 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
• IgM related immune hemolytic anemia and/or thrombocytopenia
• Nephropathy related to WM
• Amyloidosis related to WM
• Hemoglobin ≤10g/dL
• Platelet count \<100x10\^9/L
• Serum monoclonal protein \>5g/dL, even with no overt clinical symptoms Cumulative illness rating scale (CIRS) score less than 6

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 dexamethasone.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Uncontrolled bacterial, viral or fungal infection
• Active HIV, HBV or HCV infection
• 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,
• Carcinoma in situ of the breast,
• Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b).
• Uncontrolled illness including, but not limited to:

Sponsors & Collaborators

• University of Ulm: lead
• Centre Hospitalier de Lens (Co-Sponsor): collaborator

Study Sites (1)

University Hospital Ulm

Ulm, 89081, Germany

Location

Related Publications (1)

• 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.

  PMID: 36763945 BACKGROUND

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia; Neoplasms

Interventions

Dexamethasone; Rituximab; Cyclophosphamide; Bortezomib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; 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)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Martin Dreyling, MD

  National Co-Coordinating Investigator - Germany University Hospital Großhadern, Munich

  PRINCIPAL INVESTIGATOR

• Veronique Leblond, MD

  National Co-Coordinating Investigator - Groupe Hospitalier Pitié Salpêtrière France (Paris)

  PRINCIPAL INVESTIGATOR

• Pierre Morel, MD

  National Co-Coordinating Investigator - Centre Hospitalier Schaffner France (Lens cedex)

  PRINCIPAL INVESTIGATOR

• Garcia Sanz, MD

  National Co-Coordinating Investigator - University Hospital Salamanca Spain

  PRINCIPAL INVESTIGATOR

• Maria da Silva, MD

  National Co-Coordinating Investigator - Portuguese Institute of Oncology Portugal

  PRINCIPAL INVESTIGATOR

• Meletios Dimopoulos, MD

  National Co-Coordinating Investigator - University of Athens School of Medicine Athens Greece

  PRINCIPAL INVESTIGATOR

• Eva Kimby, MD

  National Co-Coordinating Investigator - Sweden, Denmark, Norway Hematology and Internal Medicine Karolinska Institutet Stockholm Sweden

  PRINCIPAL INVESTIGATOR

• Roman Hajek, MD

  National Co-Coordinating Investigator - Department of Haematooncology Ostrava Czech Republic

  PRINCIPAL INVESTIGATOR

• Wolfram Klapper, MD

  Coordinator Pathology (Germany) Department of Pathology Kiel

  STUDY CHAIR

• Sylvie Chevret

  Central Statistics (France)Department of Biostatistics and Medical Information,Hôpital Saint Louis, Paris

  STUDY CHAIR

• Christian Buske, MD

  Coordinating Investigator Germany University Hospital Ulm

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med. Christian Buske

Study Record Dates

• First Submitted: February 1, 2013
• First Posted: February 11, 2013
• Study Start: November 1, 2013
• Primary Completion: November 1, 2018
• Study Completion: April 1, 2024
• Last Updated: May 13, 2024

Record last verified: 2024-05

Locations

DE (1)