Efficacy and Safety of R-HAD Alone or in Combination With Bortezomib in Patients With Relapsed or Refractory MCL

NCT01449344 | Unknown Phase 3

• 1 other identifier: MCL2005-01
• Study Type: interventional
• Target: 128
• Locations: 2 countries
• Sites: 54

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of rituximab, high-dose ara-c and dexamethasone (r-had) alone or in combination with bortezomib in patients with relapsed or refractory mantle cell lymphoma.

Conditions

Mantle Cell Lymphoma

Keywords

relapsed; refractory

Outcome Measures

Primary Outcomes (1)

• Change from Baseline of diseased nodes and nodal masses.

  Average time frame is three weeks after the first two cycles of trial therapy and 4 to 6 weeks after the end of trial therapy. Response is always evaluated in comparison to the status before start of trial therapy. The assessment will be done with CT of all known lymphoma manifestations. In case of isolated bone marrow involvement a bone marrow aspiration/ biopsy is mandatory. A minimum of 50 % decrease in SPD (sum of the products of the greatest diameters) of the six largest nodes or nodal masses are necessary, in order to be able to evaluate it as partly remission.

  approx. 66 and 126 days after start of therapy

Study Arms (2)

R-HAD + Bortezomib

EXPERIMENTAL

Drug: Rituximab; Drug: High dose Ara-C; Drug: Dexamethasone; Drug: Bortezomib

R-HAD

ACTIVE COMPARATOR

Drug: Rituximab; Drug: High dose Ara-C; Drug: Dexamethasone

Interventions

Rituximab DRUG

Rituximab 375mg/m² IV , day 1

Also known as: Rituximab:Rituxan

R-HAD; R-HAD + Bortezomib

High dose Ara-C DRUG

Ara-C 2000 mg/m² (patients \>65 years or s/p myeloablative treatment: 1000 mg/m²) IV, d 2 and 3

Also known as: Ara-C: Cytarabine

R-HAD; R-HAD + Bortezomib

Dexamethasone DRUG

Dexamethasone 40 mg PO, day 1-4

Also known as: Dexamethasone: none

R-HAD; R-HAD + Bortezomib

Bortezomib DRUG

Bortezomib 1.5 mg/m² IV, day 1 and 4

Also known as: Bortezomib: Velcade

R-HAD + Bortezomib

Eligibility Criteria

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

You may qualify if:

• Confirmed pathological diagnosis of MCL according to WHO classification.
• Relapse or progression following 1 to 3 prior lines of anti-neoplastic standard therapy. Therapy in remission after initial induction like intensified chemotherapy for stem cell separation followed by myeloablative therapy or any kind of maintenance therapy is classified as one line of therapy with the induction therapy..
• If Rituximab was part of prior treatment, documented time to progression must be at least 12 weeks after this particular regimen.
• If high-dose Ara-C was part of prior treatment, documented time to progression must be at least 6 months after this particular regimen.
• Patients relapsed after autologous stem cell transplantation or not appropriate for myeloablative treatment.
• At least 1 measurable or assessable site of disease; in case of bone marrow infiltration only, bone marrow aspiration/ biopsy is mandatory for all staging evaluations.
• age \> 18 years
• ECOG/WHO Performance Score 0-2 unless lymphoma related.
• The following laboratory values at screening, unless lymphoma related:
• Absolute neutrophil count (ANC) \> = 1500 cells/microlitre
• Platelets \> = 100,000 cells/microlitre
• Transaminases (AST and ALT) \<=3 x upper limit of normal (ULN)
• Total bilirubin \<=2 x ULN
• Creatinine \<=2 mg/dL or calculated creatinine clearance \>=50 mL/min
• Toxic effects of previous therapy or surgery resolved to NCI CTC grade 2 or better.

You may not qualify if:

• Previous treatment with Bortezomib
• Treatment within another clinical trial within 30 days before trial entry or planned during this trial
• Anti-neoplastic (including radiation and antibody treatment) or experimental therapy within 4 weeks before planed Day 1 of Cycle 1 (Nitrosoureas within 6 weeks ) or radioimmunoconjugates or toxin immunoconjugates such as Ibritumomab tiuxetan (Zevalin™) or Tositumomab (Bexxar®) within 12 weeks before planed Day 1 of Cycle 1
• Known hypersensitivity to Rituximab, boron or mannitol.
• Active malignancy other than MCL within 5 years before Day 1 of Cycle 1, with the exception of complete resection of basal cell carcinoma, squamous cell carcinoma of the skin, or in situ malignancy.
• Active systemic infection requiring treatment.
• HIV, hepatitis B or C
• Patient has \>= grade 2 peripheral sensory neuropathy or neuropathic pain defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE).
• Symptomatic degenerative or toxic encephalopathy
• Serious medical condition (such as severe hepatic impairment, pericardial disease, acute diffuse infiltrative pulmonary disease, systemic infections etc) or psychiatric illness likely to interfere with participation in this clinical study
• Female subject is pregnant or breast-feeding (pregnancy testing is mandatory for premenopausal women).

Sponsors & Collaborators

• Prof. Dr. M. Dreyling (co-chairman): lead
• Klinikum der Universitaet Muenchen, Grosshadern: collaborator
• ClinAssess GmbH: collaborator
• GELARC Service de Pharmacovigilance, Pierre Benite: collaborator

Study Sites (54)

CH Victor Dupouy, Service hématologie

Argenteuil, 95107, France

Location

Centre Hospitalier de la côte Basque, Service hématologie

Bayonne, 64109, France

Location

CH de Blois, Service hématologie

Blois, 41016, France

Location

Institut Bergonie, Service Hématologie

Bordeaux, 33076, France

Location

CH Sud Francilien de Corbeil, Service hématologie

Corbeil-Essonnes, 91106, France

Location

Hôpital Henri Mondor, Service hématologie

Créteil, 94010, France

Location

Hôpital Albert Michallon, Service hématologie

Grenoble, 38043, France

Location

CH Mulhouse, Service hématologie

Le Mans, 68070, France

Location

Clinique Victor Hugo, Service hématologie

Le Mans, 72015, France

Location

CH du Mans, Service hématologie

Le Mans, 72037, France

Location

CHU de Nice, Service hématologie

Nice, 06202, France

Location

CHU Necker, Service d'hématologie - adulte

Paris, 75015, France

Location

Hôpital Haut Lévêque, Service hématologie

Pessac, 33604, France

Location

CHU Lyon Sud, Service hématologie

Pierre-Bénite, 69495, France

Location

Hôpital Jean Bernard, Service hématologie

Poitiers, 86021, France

Location

CH René Dubos, Service hématologie

Pontoise, 95301, France

Location

CHU Robert Debré, Service hématologie

Reims, 51092, France

Location

Hôpital Bretonneau, Service hématologie, Bâtiment H. Kaplan

Tours, 37044, France

Location

CHU Brabois, Service hématologie

Vandœuvre-lès-Nancy, 54511, France

Location

CH de Bretagne Atlantique, Service Hématologie

Vannes, 56017, France

Location

Institut Gustave ROUSSY

Villejuif, 94805, France

Location

Kreisklinik Altötting-Burghausen, Sektion Hämatologie/Onkologie und Palliativmedizin

Altötting, 84503, Germany

Location

Klinikum St. Marien, Med. Klinik II

Amberg, 92224, Germany

Location

Vivantes Klinikum Neukölln, Medizinische Klinik I - Hämatologie und Onkologie

Berlin, 12351, Germany

Location

Knappschaftskrankenhaus, Onkologische Ambulanz

Bottrop, 46242, Germany

Location

Praxis für Hämatologie/Onkologie,

Burgwedel, 30938, Germany

Location

Klinikum der Universität zu Köln, Klinik I f. Innere Medizin

Cologne, 50924, Germany

Location

Marien Hospital Düsseldorf

Düsseldorf, 40479, Germany

Location

Universitätsklinik Essen, Klinik für Hämatologie

Essen, 45147, Germany

Location

Klinikum der J.W. Goethe-Universtität Frankfurt, Medizinische Klinik II, Hämatologie/Onkologie

Frankfurt am Main, 60590, Germany

Location

Ernst-Moritz-Arndt-Universität, Hämatologie/Onkologie

Greifswald, 17475, Germany

Location

Kath. Krankenhaus Hagen gem. GmbH St.-Marien-Hospital

Hagen, 58095, Germany

Location

Asklepios Klinik St. Georg, Abteilung Hämatologie

Hamburg, 20099, Germany

Location

St.-Marien-Hopsital Gem. GmbH

Hamm, 59071, Germany

Location

Universitätsklinik des Saarlandes

Homburg/Saar, 66421, Germany

Location

Westpfalz-Klinikum GmbH, I. Medizinische Klinik

Kaiserslautern, 67653, Germany

Location

UKSH im Städt. Krankenhaus Kiel, II. Med. Klinik und Poliklinik im SSK

Kiel, 24116, Germany

Location

Praxis Dr. Vehling-Kaiser

Landshut, 84028, Germany

Location

Klinikum Magdeburg gemeinnützige GmbH, Klinik f. Hämatologie/Onkologie

Magdeburg, 39130, Germany

Location

Klinikum d. Phillips-Universität, Klinik für Innere Medizin Hämatol./Onkologie/Immunologie

Marburg, 35033, Germany

Location

Kliniken Maria Hilf GmbH (Krankenhaus St. Franziskus)

Mönchengladbach, 41063, Germany

Location

Klinikum Schwäbisch Gmünd, Zentrum Innere Medizin

Mutlangen, 73557, Germany

Location

LMU München - Klinikum Großhadern Medizinische Klinik III

München, 81377, Germany

Location

Klinikum Nord Nürnberg, 5. Med. Klinik, Onkologie/Hämatologie

Nuremberg, 90419, Germany

Location

Schlossberg Klinik, Oberstaufen Internistische Onkologie

Oberstaufen, 87534, Germany

Location

Diakonie Klinikum Jung Stilling Krankenhaus

Siegen, 57074, Germany

Location

Diakonieklinikum Stuttgart, Medizinische Klinik II

Stuttgart, 70176, Germany

Location

Robert-Bosch-Krankenhaus, Hämatologie/Onkologie

Stuttgart, 70376, Germany

Location

Mutterhaus der Borromäerinnen, Medizinische Abteilung

Trier, 54219, Germany

Location

Krankenhaus der Barmherzigen Brüder, 1. Medizinische Abteilung

Trier, 54292, Germany

Location

Universitätsklinikum Ulm, Innere Medizin III

Ulm, 89081, Germany

Location

Harz-Klinikum Wernigerode-Blankenburg GmbH, Innere Medizin, Hämato-Onkologie und Palliativmedizin

Wernigerode, 38855, Germany

Location

Ammerland-Klinik GmbH, Klinik für innere Medizin

Westerstede, 26655, Germany

Location

Heinrich-Braun-Krankenhaus, Klinik für Innere Medizin III

Zwickau, 08060, Germany

Location

Related Publications (1)

• Fischer L, Jiang L, Durig J, Schmidt C, Stilgenbauer S, Bouabdallah K, Solal-Celigny P, Scholz CW, Feugier P, de Wit M, Trappe RU, Hallek M, Graeven U, Hanel M, Hoffmann M, Delwail V, Macro M, Greiner J, Giagounidis AAN, Dargel B, Durot E, Foussard C, Silkenstedt E, Weigert O, Pott C, Klapper W, Hiddemann W, Unterhalt M, Hoster E, Ribrag V, Dreyling M. The addition of bortezomib to rituximab, high-dose cytarabine and dexamethasone in relapsed or refractory mantle cell lymphoma-a randomized, open-label phase III trial of the European mantle cell lymphoma network. Leukemia. 2024 Jun;38(6):1307-1314. doi: 10.1038/s41375-024-02254-2. Epub 2024 Apr 27.

  PMID: 38678093 DERIVED

MeSH Terms

Conditions

Lymphoma, Mantle-Cell; Recurrence

Interventions

Rituximab; Cytarabine; Dexamethasone; Bortezomib

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines

Study Officials

• Martin Dreyling, MD

  Klinikum der Universität München, Grosshadern

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Coordinating investigator, Germany

Study Record Dates

• First Submitted: September 28, 2011
• First Posted: October 10, 2011
• Study Start: May 9, 2009
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: March 7, 2017

Record last verified: 2017-03

Locations

DE (33); FR (21)