Efficacy and Safety of R-HAD Alone or in Combination With Bortezomib in Patients With Relapsed or Refractory MCL
Conditions
Mantle Cell Lymphoma
Conditions: official terms
Lymphoma, Mantle-Cell
Conditions: Keywords
relapsed, refractory
Study Type
Interventional
Study Phase
Phase 3
Study Design
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Rituximab Type: Drug
Name: High dose Ara-C Type: Drug
Name: Dexamethasone Type: Drug
Name: Bortezomib Type: Drug
Overall Status
Recruiting
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.
Detailed Description
This study is a prospective, randomized, multicenter, open-label phase III clinical trial to compare the efficacy and safety of Bortezomib in combination with Rituximab, high-dose Ara-C and dexamethasone (R-HAD) to R-HAD alone in patients with relapsed or refractory MCL after or not eligible for myeloablative treatment. The primary endpoint is time to treatment failure (TTF). Secondary endpoints are the complete response (CR) rate, the overall response (CR,PR) rate, the progression-free survival (PFS), the progression free survival of responders, the time to next lymphoma treatment, overall survival (OS), safety and tolerability of Rituximab, high-dose Ara-C and dexamethasone alone or in combination with Bortezomib. Study arms will be compared to each other to evaluate the impact of additional Bortezomib. Study arms will also be compared to historical controls.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

- 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.

- Premenopausal fertile females must agree to use a highly effective method of birth control for the duration of the therapy. A highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner.

- Men must agree not to father a child for the duration of therapy and must agree to advice a female partner to use a highly effective method of birth control.

- Written informed consent before performance of any study-related procedure.

Exclusion Criteria:

- 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).
Locations
CH Victor Dupouy, Service hématologie
Argenteuil Cedex, France
Status: Recruiting
Contact: Laurent SUTTON, Dr - +33 1 34 23 22 39 - laurent.sutton@ch-argenteuil.fr
Centre Hospitalier de la côte Basque, Service hématologie
Bayonne, France
Status: Recruiting
Contact: Anne Banos, Dr. - +33 5 49 44 - abanos@ch-cotebasque.fr
CH de Blois, Service hématologie
Blois, France
Status: Recruiting
Contact: Abderrazak El Yamani, Dr. - +33 2 54 55 - elyamaa@ch-blois.fr
Institut Bergonie, Service Hématologie
Bordeaux, France
Status: Recruiting
Contact: Pierre Soubeyran, Prof. - +33 5 56 33 - p.soubeyran@bordeaux.unicancer.fr
CH Sud Francilien de Corbeil, Service hématologie
Corbeil Essonnes, France
Status: Recruiting
Contact: Bertrand Joly, Dr. - +33 1 60 90 - bertrand.joly@ch-sud-francilien.fr
Hôpital Henri Mondor, Service hématologie
Créteil, France
Status: Recruiting
Contact: Corinne Haioun, Dr - +33 1 49 81 - corinne.haioun@hmn.aphp.fr
Hôpital Albert Michallon, Service hématologie
Grenoble, France
Status: Recruiting
Contact: Rémy Gressin, Dr. - +33 4 76 76 - RGressin@chu-grenoble.fr
CH du Mans, Service hématologie
Le Mans, France
Status: Recruiting
Contact: Kamel Laribi, Dr. - +33 2 43 43 - klaribi@ch-lemans.fr
CH Mulhouse, Service hématologie
Le Mans, France
Status: Recruiting
Contact: Jean-Claude Eisenmann, Dr. - +33 3 89 64 - eisenmannj@ch-mulhouse.fr
Clinique Victor Hugo, Service hématologie
Le Mans, France
Status: Recruiting
Contact: Philippe Solal-Celigny, Dr. - +33 2 43 47 - p.solal-celigny@cjb72.org
CHU de Nice, Service hématologie
Nice, France
Status: Recruiting
Contact: Nicolas Mounier, Dr. - +33 4 92 03 - mounier.n@chu-nice.fr
CHU Necker, Service d'hématologie - adulte
Paris, France
Status: Recruiting
Contact: Richard Delarue, Dr. - +33 1 44 49 - richard.delarue@nck.aphp.fr
Hôpital Haut Lévêque, Service hématologie
Pessac, France
Status: Recruiting
Contact: Noel Milpied, Dr - +33 5 57 65 - noel.milpied@chu-bordeaux.fr
CHU Lyon Sud, Service hématologie
Pierre Benite, France
Status: Recruiting
Contact: Bertrand Coiffier, Prof. - +33 4 78 86 - bertrand.coiffier@chu-lyon.fr
Hôpital Jean Bernard, Service hématologie
Poitiers, France
Status: Recruiting
Contact: Vincent Delwail, Dr. - +33 5 49 44 - v.delwail@chu-poitiers.fr
CH René Dubos, Service hématologie
Pontoise, France
Status: Recruiting
Contact: Hugo Gonzalez, Dr. - +33 1 30 75 - hugo.gonzalez@ch-pontoise.fr
CHU Robert Debré, Service hématologie
Reims, France
Status: Recruiting
Contact: Alain Delmer, Dr. - +33 3 26 78 - adelmer@chu-reims.fr
Hôpital Bretonneau, Service hématologie, Bâtiment H. Kaplan
Tours, France
Status: Recruiting
Contact: Emmanuel GYAN, Dr - +33 2 18 37 06 - e.gyan@chu-tours.fr
CHU Brabois, Service hématologie
Vandoeuvre les Nancy, France
Status: Recruiting
Contact: Pierre Feugier, Dr. - +33 3 83 15 32 82 - p.feugier@chu-nancy.fr
CH de Bretagne Atlantique, Service Hématologie
Vannes, France
Status: Recruiting
Contact: Henry Jardel, Dr. - +33 2 97 01 - henry.jardel@ch-bretagne-atlantique.fr
Institut Gustave ROUSSY
Villejuif, France
Status: Recruiting
Contact: Vincent Ribrag, Dr. - +33 1 42 11 45 07 - Vincent.RIBRAG@igr.fr
Kreisklinik Altötting-Burghausen, Sektion Hämatologie/Onkologie und Palliativmedizin
Altötting, Germany
Status: Recruiting
Contact: Johannes Spes, Dr. med. - +498671 509
Klinikum St. Marien, Med. Klinik II
Amberg, Germany
Status: Recruiting
Contact: Ludwig Fischer von Weikersthal, Dr. - +499621-381637 - weikersthal.ludwig@klinikum-amberg.de
Vivantes Klinikum Neukölln, Medizinische Klinik I - Hämatologie und Onkologie
Berlin, Germany
Status: Recruiting
Contact: Maike de Wit, Prof. - 030-130 14 - maike.dewit@vivantes.de
Knappschaftskrankenhaus, Onkologische Ambulanz
Bottrop, Germany
Status: Recruiting
Contact: Guido Trenn, PD Dr. med. - +492041-15 - guido.trenn@kk-bottrop.de
Praxis für Hämatologie/Onkologie,
Burgwedel, Germany
Status: Recruiting
Contact: Godehard Obst, Dr. med. - +495139-6555 - dr.-godehard-obst@t-online.de
Marien Hospital Düsseldorf
Düsseldorf, Germany
Status: Not yet recruiting
Contact: H.J. Schütte, Prof. Dr. - +49211-4400 - onkologie@marien-hospital.de
Universitätsklinik Essen, Klinik für Hämatologie
Essen, Germany
Status: Recruiting
Contact: Jan Dürig, PD Dr. - +49201-723 - jan.duerig@uk-essen.de
Klinikum der J.W. Goethe-Universtität Frankfurt, Medizinische Klinik II, Hämatologie/Onkologie
Frankfurt am Main, Germany
Status: Recruiting
Contact: Lothar Bergmann, Prof. Dr. - +4969-6301 - L.Bergmann@em.uni-frankfurt.de
Ernst-Moritz-Arndt-Universität, Hämatologie/Onkologie
Greifswald, Germany
Status: Recruiting
Contact: Gottfried Dölken, Prof. Dr. - +493834-86 - dermatologie@uni-greifswald.de
Kath. Krankenhaus Hagen gem. GmbH St.-Marien-Hospital
Hagen, Germany
Status: Recruiting
Contact: Hans-Walter Lindemann, Dr. - +49 2331/ 129 - w.lindemann@kkh-hagen.de
Asklepios Klinik St. Georg, Abteilung Hämatologie
Hamburg, Germany
Status: Recruiting
Contact: Maike Nickelsen, Dr. - +4940 18 18-85 - m.nickelsen@asklepios.com
St.-Marien-Hopsital Gem. GmbH
Hamm, Germany
Status: Recruiting
Contact: Heinz Dürk, Dr. - +492381-18 - heinz.duerk@t-online.de
Universitätsklinik des Saarlandes
Homburg/Saar, Germany
Status: Recruiting
Contact: Michael Pfreundschuh, Prof. Dr. - +496841-16230 - michael.pfreundschuh@uniklinikum-saarland.de
Westpfalz-Klinikum GmbH, I. Medizinische Klinik
Kaiserslautern, Germany
Status: Recruiting
Contact: Stefan Mahlmann, Dr. - +49 631 - 203 - smahlmann@westpfalz-klinikum.de
UKSH im Städt. Krankenhaus Kiel, II. Med. Klinik und Poliklinik im SSK
Kiel, Germany
Status: Recruiting
Contact: Michael Kneba, Prof. - +49 431-1697 - sekretariat@med2.uni-kiel.de
Klinikum der Universität zu Köl, Klinik I f. Innere Medizin
Köln, Germany
Status: Recruiting
Contact: Kai Hübel, PD Dr. - +49221-478 - kai.huebel@uk-koeln.de
Praxis Dr. Vehling-Kaiser
Landshut, Germany
Status: Recruiting
Contact: Ursula Vehling-Kaiser, Dr. med. - +49871-27- - studien@vehling-kaiser.de
Klinikum Magdeburg gemeinnützige GmbH, Klinik f. Hämatologie/Onkologie
Magdeburg, Germany
Status: Recruiting
Contact: Christoph Kahl, PD Dr. med. - +49391-791 - christoph.kahl@klinikum-magdeburg.de
Klinikum Magdeburg gemeinnützige GmbH, Klinik f. Hämatologie/Onkologie
Magdeburg, Germany
Status: Recruiting
Contact: Christoph Kahl, PD Dr. - +49 391-791 - christoph.kahl@klinikum-magdeburg.de
Klinikum d. Phillips-Universität, Klinik für Innere Medizin Hämatol./Onkologie/Immunologie
Marburg, Germany
Status: Not yet recruiting
Contact: Andreas Neubauer, Prof. Dr. - +496421-586 - Andreas.Neubauer@med.uni-marburg.de
Klinikum Schwäbisch Gmünd, Zentrum Innere Medizin
Mutlangen, Germany
Status: Recruiting
Contact: Holger F. Hebart, Prof. Dr. - +497171 / 701- - holger.hebart@stauferklinikum.de
Kliniken Maria Hilf GmbH (Krankenhaus St. Franziskus)
Mönchengladbach, Germany
Status: Recruiting
Contact: U. Graeven, PD Dr. - +492161-892- - innere1@mariahilf.de
LMU München - Klinikum Großhadern Medizinische Klinik III
München, Germany
Status: Recruiting
Contact: Roswitha Forstpointner, Dr - +4989-7095 - roswitha.forstpointner@med.uni-muenchen.de
Klinikum Nord Nürnberg, 5. Med. Klinik, Onkologie/Hämatologie
Nürnberg, Germany
Status: Recruiting
Contact: Kerstin Schäfer-Eckart, Dr. - +49 911-398 - kerstin.schaefer-eckart@klinikum-nuernberg.de
Schlossberg Klinik, Oberstaufen Internistische Onkologie
Oberstaufen, Germany
Status: Not yet recruiting
Contact: Thomas Licht, Prof. Dr. - +498386-701 - thomas.licht@helios-kliniken.de
Diakonie Klinikum Jung Stilling Krankenhaus
Siegen, Germany
Status: Recruiting
Contact: Martin Klump, Dr. - +49271-333-4569 - martin.klump@diakonie-sw.de
Diakonieklinikum Stuttgart, Medizinische Klinik II
Stuttgart, Germany
Status: Recruiting
Contact: Elke Heidemann, Prof. Dr. - +49711-991 - heidemann@diak-stuttgart.de
Robert-Bosch-Krankenhaus, Hämatologie/Onkologie
Stuttgart, Germany
Status: Recruiting
Contact: Walter Aulitzky, Prof. Dr. - +49711-8101 - walter.aulitzky@rbk.de
Krankenhaus der Barmherzigen Brüder, 1. Medizinische Abteilung
Trier, Germany
Status: Recruiting
Contact: Heinz Kirchen, Dr. med. - +49651-208 - h.kirchen@bk-trier.de
Mutterhaus der Borromäerinnen, Medizinische Abteilung
Trier, Germany
Status: Recruiting
Contact: Michael R. Clemens, Prof. Dr. - +49651-947 - clemens@mutterhaus.de
Universitätsklinikum Ulm, Innere Medizin III
Ulm, Germany
Status: Recruiting
Contact: Stephan Stilgenbauer, Prof. Dr. - +49731-500 - stephan.stilgenbauer@uni-ulm.de
Harz-Klinikum Wernigerode-Blankenburg GmbH, Innere Medizin, Hämato-Onkologie und Palliativmedizin
Wernigerode, Germany
Status: Recruiting
Contact: Bijan Zomorodbakhsch, Dr. med. - +493943-611 - onkologie@harz-klinikum.de
Ammerland-Klinik GmbH, Klinik für innere Medizin
Westerstede, Germany
Status: Recruiting
Contact: Detlev Kohl, Dr. - +49 4488-50 - detlev.kohl@ammerland-klinik.de
Heinrich-Braun-Krankenhaus, Klinik für Innere Medizin III
Zwickau, Germany
Status: Recruiting
Contact: Ute Kreibich, Dr. - + 49 375/51 - ute.kreibich@hbk-zwickau.de
Start Date
November 2011
Completion Date
September 2016
Sponsors
Dr. M. Dreyling (co-chairman)
Source
European Mantle Cell Lymphoma Network
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page