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

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified September 2012 by European Mantle Cell Lymphoma Network.
Recruitment status was:  Recruiting
Klinikum der Universitaet Muenchen, Grosshadern
ClinAssess GmbH
GELARC Service de Pharmacovigilance, Pierre Benite
Information provided by (Responsible Party):
Dr. M. Dreyling (co-chairman), European Mantle Cell Lymphoma Network Identifier:
First received: September 28, 2011
Last updated: September 6, 2012
Last verified: September 2012
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.

Condition Intervention Phase
Mantle Cell Lymphoma
Drug: Rituximab
Drug: High dose Ara-C
Drug: Dexamethasone
Drug: Bortezomib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

Further study details as provided by European Mantle Cell Lymphoma Network:

Primary Outcome Measures:
  • Change from Baseline of diseased nodes and nodal masses. [ Time Frame: approx. 66 and 126 days after start of therapy ]

    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.

Estimated Enrollment: 175
Study Start Date: November 2011
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: R-HAD + Bortezomib Drug: Rituximab
Rituximab 375mg/m² IV , day 1
Other Name: Rituximab:Rituxan
Drug: High dose Ara-C
Ara-C 2000 mg/m² (patients >65 years or s/p myeloablative treatment: 1000 mg/m²) IV, d 2 and 3
Other Name: Ara-C: Cytarabine
Drug: Dexamethasone
Dexamethasone 40 mg PO, day 1-4
Other Name: Dexamethasone: none
Drug: Bortezomib
Bortezomib 1.5 mg/m² IV, day 1 and 4
Other Name: Bortezomib: Velcade
Active Comparator: R-HAD Drug: Rituximab
Rituximab 375mg/m² IV , day 1
Other Name: Rituximab:Rituxan
Drug: High dose Ara-C
Ara-C 2000 mg/m² (patients >65 years or s/p myeloablative treatment: 1000 mg/m²) IV, d 2 and 3
Other Name: Ara-C: Cytarabine
Drug: Dexamethasone
Dexamethasone 40 mg PO, day 1-4
Other Name: Dexamethasone: none

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.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01449344

Contact: Martin Dreyling, Professor +49 (89) 7095 ext 2202

  Hide Study Locations
CH Victor Dupouy, Service hématologie Recruiting
Argenteuil Cedex, France, 95107
Contact: Laurent SUTTON, Dr    +33 1 34 23 22 39   
Principal Investigator: Laurent SUTTON, Dr         
Centre Hospitalier de la côte Basque, Service hématologie Recruiting
Bayonne, France, 64109
Contact: Anne Banos, Dr.    +33 5 49 44 ext 38 32   
Principal Investigator: Anne Banos, Dr.         
CH de Blois, Service hématologie Recruiting
Blois, France, 41016
Contact: Abderrazak El Yamani, Dr.    +33 2 54 55 ext 65 04   
Principal Investigator: Abderrazak El Yamani, Dr.         
Institut Bergonie, Service Hématologie Recruiting
Bordeaux, France, 33076
Contact: Pierre Soubeyran, Prof.    +33 5 56 33 ext 32 67   
Principal Investigator: Pierre Soubeyran, Prof.         
CH Sud Francilien de Corbeil, Service hématologie Recruiting
Corbeil Essonnes, France, 91106
Contact: Bertrand Joly, Dr.    +33 1 60 90 ext 31 78   
Principal Investigator: Bertrand Joly, Dr.         
Hôpital Henri Mondor, Service hématologie Recruiting
Créteil, France, 94010
Contact: Corinne Haioun, Dr    +33 1 49 81 ext 21 71   
Principal Investigator: Corinne Haioun, Dr.         
Hôpital Albert Michallon, Service hématologie Recruiting
Grenoble, France, 38043
Contact: Rémy Gressin, Dr.    +33 4 76 76 ext 59 53   
Principal Investigator: Rémy Gressin, Dr.         
CH Mulhouse, Service hématologie Recruiting
Le Mans, France, 68070
Contact: Jean-Claude Eisenmann, Dr.    +33 3 89 64 ext 77 55   
Principal Investigator: Jean-Claude Eisenmann, Dr.         
Clinique Victor Hugo, Service hématologie Recruiting
Le Mans, France, 72015
Contact: Philippe Solal-Celigny, Dr.    +33 2 43 47 ext 94 93   
Principal Investigator: Philippe Solal-Celigny, Dr.         
CH du Mans, Service hématologie Recruiting
Le Mans, France, 72037
Contact: Kamel Laribi, Dr.    +33 2 43 43 ext 43 63   
Principal Investigator: Kamel Laribi, Dr.         
CHU de Nice, Service hématologie Recruiting
Nice, France, 06202
Contact: Nicolas Mounier, Dr.    +33 4 92 03 ext 58 41   
Principal Investigator: Nicolas Mounier, Dr.         
CHU Necker, Service d'hématologie - adulte Recruiting
Paris, France, 75015
Contact: Richard Delarue, Dr.    +33 1 44 49 ext 52 96   
Principal Investigator: Richard Delarue, Dr.         
Hôpital Haut Lévêque, Service hématologie Recruiting
Pessac, France, 33604
Contact: Noel Milpied, Dr    +33 5 57 65 ext 65 11   
Principal Investigator: Noel Milpied, Dr.         
CHU Lyon Sud, Service hématologie Recruiting
Pierre Benite, France, 69495
Contact: Bertrand Coiffier, Prof.    +33 4 78 86 ext 43 01   
Principal Investigator: Bertrand Coiffier, Prof.         
Hôpital Jean Bernard, Service hématologie Recruiting
Poitiers, France, 86021
Contact: Vincent Delwail, Dr.    +33 5 49 44 ext 44 72   
Principal Investigator: Vincent Delwail, Dr.         
CH René Dubos, Service hématologie Recruiting
Pontoise, France, 95301
Contact: Hugo Gonzalez, Dr.    +33 1 30 75 ext 42 82   
Principal Investigator: Hugo Gonzalez, Dr.         
CHU Robert Debré, Service hématologie Recruiting
Reims, France, 51092
Contact: Alain Delmer, Dr.    +33 3 26 78 ext 36 44   
Principal Investigator: Alain Delmer, Dr.         
Hôpital Bretonneau, Service hématologie, Bâtiment H. Kaplan Recruiting
Tours, France, 37044
Contact: Emmanuel GYAN, Dr    +33 2 18 37 06 ext 09   
Principal Investigator: Emmanuel GYAN, Dr         
CHU Brabois, Service hématologie Recruiting
Vandoeuvre les Nancy, France, 54511
Contact: Pierre Feugier, Dr.    +33 3 83 15 32 82   
Principal Investigator: Pierre Feugier, Dr.         
CH de Bretagne Atlantique, Service Hématologie Recruiting
Vannes, France, 56017
Contact: Henry Jardel, Dr.    +33 2 97 01 ext 45 64   
Principal Investigator: Henry Jardel, Dr.         
Institut Gustave ROUSSY Recruiting
Villejuif, France, 94805
Contact: Vincent Ribrag, Dr.    +33 1 42 11 45 07   
Principal Investigator: Vince Ribrag, Dr.         
Kreisklinik Altötting-Burghausen, Sektion Hämatologie/Onkologie und Palliativmedizin Recruiting
Altötting, Germany, 84503
Contact: Johannes Spes, Dr. med.    +498671 509 ext 0      
Principal Investigator: Johannes Spes, Dr. med.         
Klinikum St. Marien, Med. Klinik II Recruiting
Amberg, Germany, 92224
Contact: Ludwig Fischer von Weikersthal, Dr.    +499621-381637   
Principal Investigator: Ludwig Fischer von Weikersthal, Dr.         
Vivantes Klinikum Neukölln, Medizinische Klinik I - Hämatologie und Onkologie Recruiting
Berlin, Germany, 12351
Contact: Maike de Wit, Prof.    030-130 14 ext 2251   
Principal Investigator: Maike de Wit, Prof.         
Knappschaftskrankenhaus, Onkologische Ambulanz Recruiting
Bottrop, Germany, 46242
Contact: Guido Trenn, PD Dr. med.    +492041-15 ext 1511   
Principal Investigator: Guido Trenn, PD Dr. med.         
Praxis für Hämatologie/Onkologie, Recruiting
Burgwedel, Germany, 30938
Contact: Godehard Obst, Dr. med.    +495139-6555   
Principal Investigator: Godehard Obst, Dr. med.         
Marien Hospital Düsseldorf Not yet recruiting
Düsseldorf, Germany, 40479
Contact: H.J. Schütte, Prof. Dr.    +49211-4400 ext 2500   
Principal Investigator: H.-J. Schütte, Prof.         
Universitätsklinik Essen, Klinik für Hämatologie Recruiting
Essen, Germany, 45147
Contact: Jan Dürig, PD Dr.    +49201-723 ext 2417   
Principal Investigator: Jan Dürig, PD Dr. med.         
Klinikum der J.W. Goethe-Universtität Frankfurt, Medizinische Klinik II, Hämatologie/Onkologie Recruiting
Frankfurt am Main, Germany, 60590
Contact: Lothar Bergmann, Prof. Dr.    +4969-6301 ext 5121   
Principal Investigator: Lothar Bergmann, Prof. Dr.         
Ernst-Moritz-Arndt-Universität, Hämatologie/Onkologie Recruiting
Greifswald, Germany, 17475
Contact: Gottfried Dölken, Prof. Dr.    +493834-86 ext 6698   
Principal Investigator: Gottfried Dölken, Prof. Dr.         
Kath. Krankenhaus Hagen gem. GmbH St.-Marien-Hospital Recruiting
Hagen, Germany, 58095
Contact: Hans-Walter Lindemann, Dr.    +49 2331/ 129 ext 250   
Principal Investigator: Hans-Walter Lindemann, Dr.         
Asklepios Klinik St. Georg, Abteilung Hämatologie Recruiting
Hamburg, Germany, 20099
Contact: Maike Nickelsen, Dr.    +4940 18 18-85 ext 20 05   
Principal Investigator: Maike Nickelsen, Dr.         
St.-Marien-Hopsital Gem. GmbH Recruiting
Hamm, Germany, 59071
Contact: Heinz Dürk, Dr.    +492381-18 ext -2250   
Principal Investigator: Heinz Dürk, Dr.         
Universitätsklinik des Saarlandes Recruiting
Homburg/Saar, Germany, 66421
Contact: Michael Pfreundschuh, Prof. Dr.    +496841-16230 ext 02   
Principal Investigator: Michael Pfreundschuh, Prof. Dr.         
Westpfalz-Klinikum GmbH, I. Medizinische Klinik Recruiting
Kaiserslautern, Germany, 67653
Contact: Stefan Mahlmann, Dr.    +49 631 - 203 ext 1624   
Principal Investigator: Stefan Mahlmann, Dr.         
UKSH im Städt. Krankenhaus Kiel, II. Med. Klinik und Poliklinik im SSK Recruiting
Kiel, Germany, 24116
Contact: Michael Kneba, Prof.    +49 431-1697 ext 1201   
Principal Investigator: Michael Kneba, Prof.         
Klinikum der Universität zu Köl, Klinik I f. Innere Medizin Recruiting
Köln, Germany, 50924
Contact: Kai Hübel, PD Dr.    +49221-478 ext 3583   
Principal Investigator: Kai Huebel, PD Dr.         
Praxis Dr. Vehling-Kaiser Recruiting
Landshut, Germany, 84028
Contact: Ursula Vehling-Kaiser, Dr. med.    +49871-27- ext 5381   
Principal Investigator: Ursula Vehling-Kaiser, Dr. med.         
Klinikum Magdeburg gemeinnützige GmbH, Klinik f. Hämatologie/Onkologie Recruiting
Magdeburg, Germany, 39130
Contact: Christoph Kahl, PD Dr. med.    +49391-791 ext 5640   
Principal Investigator: Christoph Kahl, PD Dr. med.         
Klinikum Magdeburg gemeinnützige GmbH, Klinik f. Hämatologie/Onkologie Recruiting
Magdeburg, Germany, 39130
Contact: Christoph Kahl, PD Dr.    +49 391-791 ext 5640   
Principal Investigator: Christoph Kahl, PD Dr.         
Klinikum d. Phillips-Universität, Klinik für Innere Medizin Hämatol./Onkologie/Immunologie Not yet recruiting
Marburg, Germany, 35033
Contact: Andreas Neubauer, Prof. Dr.    +496421-586 ext 2755   
Principal Investigator: Andreas Neubauer, Prof. Dr.         
Klinikum Schwäbisch Gmünd, Zentrum Innere Medizin Recruiting
Mutlangen, Germany, 73557
Contact: Holger F. Hebart, Prof. Dr.    +497171 / 701- ext 1302   
Principal Investigator: Holger F. Hebart, Prof. Dr.         
Kliniken Maria Hilf GmbH (Krankenhaus St. Franziskus) Recruiting
Mönchengladbach, Germany, 41063
Contact: U. Graeven, PD Dr.    +492161-892- ext 2212, -2201   
Principal Investigator: U. Graeven, PD Dr.         
LMU München - Klinikum Großhadern Medizinische Klinik III Recruiting
München, Germany, 81377
Contact: Roswitha Forstpointner, Dr    +4989-7095 ext 2551   
Principal Investigator: Roswitha Forstpointner, Dr.         
Klinikum Nord Nürnberg, 5. Med. Klinik, Onkologie/Hämatologie Recruiting
Nürnberg, Germany, 90419
Contact: Kerstin Schäfer-Eckart, Dr.    +49 911-398 ext 113622   
Principal Investigator: Kerstin Schäfer-Eckart, Dr.         
Schlossberg Klinik, Oberstaufen Internistische Onkologie Not yet recruiting
Oberstaufen, Germany, 87534
Contact: Thomas Licht, Prof. Dr.    +498386-701 ext 0   
Principal Investigator: Thomas Licht, Prof. Dr.         
Diakonie Klinikum Jung Stilling Krankenhaus Recruiting
Siegen, Germany, 57074
Contact: Martin Klump, Dr.    +49271-333-4569   
Principal Investigator: Martin Klump, Dr.         
Diakonieklinikum Stuttgart, Medizinische Klinik II Recruiting
Stuttgart, Germany, 70176
Contact: Elke Heidemann, Prof. Dr.    +49711-991 ext 3515   
Principal Investigator: Elke Heidemann, Prof. Dr.         
Robert-Bosch-Krankenhaus, Hämatologie/Onkologie Recruiting
Stuttgart, Germany, 70376
Contact: Walter Aulitzky, Prof. Dr.    +49711-8101 ext 3506   
Principal Investigator: Walter Aulitzky, Prof. Dr.         
Mutterhaus der Borromäerinnen, Medizinische Abteilung Recruiting
Trier, Germany, 54219
Contact: Michael R. Clemens, Prof. Dr.    +49651-947 ext 2377   
Principal Investigator: Michael R. Clemens, Prof. Dr.         
Krankenhaus der Barmherzigen Brüder, 1. Medizinische Abteilung Recruiting
Trier, Germany, 54292
Contact: Heinz Kirchen, Dr. med.    +49651-208 ext 2662   
Principal Investigator: Heinz Kirchen, Dr. med.         
Universitätsklinikum Ulm, Innere Medizin III Recruiting
Ulm, Germany, 89081
Contact: Stephan Stilgenbauer, Prof. Dr.    +49731-500 ext 45501   
Principal Investigator: Stephan Stilgenbauer, Prof. Dr.         
Harz-Klinikum Wernigerode-Blankenburg GmbH, Innere Medizin, Hämato-Onkologie und Palliativmedizin Recruiting
Wernigerode, Germany, 38855
Contact: Bijan Zomorodbakhsch, Dr. med.    +493943-611 ext 205   
Principal Investigator: Bijan Zomorodbakhsch, Dr. med.         
Ammerland-Klinik GmbH, Klinik für innere Medizin Recruiting
Westerstede, Germany, 26655
Contact: Detlev Kohl, Dr.    +49 4488-50 ext 2825   
Principal Investigator: Detlev Kohl, Dr.         
Heinrich-Braun-Krankenhaus, Klinik für Innere Medizin III Recruiting
Zwickau, Germany, 08060
Contact: Ute Kreibich, Dr.    + 49 375/51 ext 2333   
Principal Investigator: Ute Kreibich, Dr.         
Sponsors and Collaborators
Dr. M. Dreyling (co-chairman)
Klinikum der Universitaet Muenchen, Grosshadern
ClinAssess GmbH
GELARC Service de Pharmacovigilance, Pierre Benite
Principal Investigator: Martin Dreyling, MD Klinikum der Universität München, Grosshadern
  More Information

Responsible Party: Dr. M. Dreyling (co-chairman), Coordinating investigator, Germany, European Mantle Cell Lymphoma Network Identifier: NCT01449344     History of Changes
Other Study ID Numbers: MCL2005-01 
Study First Received: September 28, 2011
Last Updated: September 6, 2012

Keywords provided by European Mantle Cell Lymphoma Network:

Additional relevant MeSH terms:
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on February 24, 2017