Efficacy and Safety of R-HAD Alone or in Combination With Bortezomib in Patients With Relapsed or Refractory MCL
- Conditions
- Mantle Cell Lymphoma
- Interventions
- Registration Number
- NCT01449344
- Lead Sponsor
- Prof. Dr. M. Dreyling (co-chairman)
- 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.
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 128
- 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.
- 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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description R-HAD Dexamethasone - R-HAD Rituximab - R-HAD + Bortezomib Rituximab - R-HAD + Bortezomib High dose Ara-C - R-HAD + Bortezomib Dexamethasone - R-HAD High dose Ara-C - R-HAD + Bortezomib Bortezomib -
- Primary Outcome Measures
Name Time Method Change from Baseline of diseased nodes and nodal masses. 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (54)
Hôpital Henri Mondor, Service hématologie
🇫🇷Créteil, France
CHU de Nice, Service hématologie
🇫🇷Nice, France
Asklepios Klinik St. Georg, Abteilung Hämatologie
🇩🇪Hamburg, Germany
Kreisklinik Altötting-Burghausen, Sektion Hämatologie/Onkologie und Palliativmedizin
🇩🇪Altötting, Germany
Marien Hospital Düsseldorf
🇩🇪Düsseldorf, Germany
Clinique Victor Hugo, Service hématologie
🇫🇷Le Mans, France
Knappschaftskrankenhaus, Onkologische Ambulanz
🇩🇪Bottrop, Germany
Klinikum St. Marien, Med. Klinik II
🇩🇪Amberg, Germany
Vivantes Klinikum Neukölln, Medizinische Klinik I - Hämatologie und Onkologie
🇩🇪Berlin, Germany
Praxis für Hämatologie/Onkologie,
🇩🇪Burgwedel, Germany
CH Victor Dupouy, Service hématologie
🇫🇷Argenteuil Cedex, France
Kath. Krankenhaus Hagen gem. GmbH St.-Marien-Hospital
🇩🇪Hagen, Germany
CHU Necker, Service d'hématologie - adulte
🇫🇷Paris, France
Westpfalz-Klinikum GmbH, I. Medizinische Klinik
🇩🇪Kaiserslautern, Germany
Universitätsklinik Essen, Klinik für Hämatologie
🇩🇪Essen, Germany
Klinikum Magdeburg gemeinnützige GmbH, Klinik f. Hämatologie/Onkologie
🇩🇪Magdeburg, Germany
Klinikum Nord Nürnberg, 5. Med. Klinik, Onkologie/Hämatologie
🇩🇪Nürnberg, Germany
Schlossberg Klinik, Oberstaufen Internistische Onkologie
🇩🇪Oberstaufen, Germany
UKSH im Städt. Krankenhaus Kiel, II. Med. Klinik und Poliklinik im SSK
🇩🇪Kiel, Germany
Praxis Dr. Vehling-Kaiser
🇩🇪Landshut, Germany
Diakonie Klinikum Jung Stilling Krankenhaus
🇩🇪Siegen, Germany
Ernst-Moritz-Arndt-Universität, Hämatologie/Onkologie
🇩🇪Greifswald, Germany
Universitätsklinik des Saarlandes
🇩🇪Homburg/Saar, Germany
Klinikum der Universität zu Köln, Klinik I f. Innere Medizin
🇩🇪Köln, Germany
Universitätsklinikum Ulm, Innere Medizin III
🇩🇪Ulm, Germany
Heinrich-Braun-Krankenhaus, Klinik für Innere Medizin III
🇩🇪Zwickau, Germany
Centre Hospitalier de la côte Basque, Service hématologie
🇫🇷Bayonne, France
CH Sud Francilien de Corbeil, Service hématologie
🇫🇷Corbeil Essonnes, France
Hôpital Albert Michallon, Service hématologie
🇫🇷Grenoble, France
Hôpital Haut Lévêque, Service hématologie
🇫🇷Pessac, France
CHU Lyon Sud, Service hématologie
🇫🇷Pierre Benite, France
Hôpital Jean Bernard, Service hématologie
🇫🇷Poitiers, France
CH René Dubos, Service hématologie
🇫🇷Pontoise, France
CHU Robert Debré, Service hématologie
🇫🇷Reims, France
Hôpital Bretonneau, Service hématologie, Bâtiment H. Kaplan
🇫🇷Tours, France
CHU Brabois, Service hématologie
🇫🇷Vandoeuvre les Nancy, France
CH de Bretagne Atlantique, Service Hématologie
🇫🇷Vannes, France
Institut Gustave ROUSSY
🇫🇷Villejuif, France
CH de Blois, Service hématologie
🇫🇷Blois, France
Institut Bergonie, Service Hématologie
🇫🇷Bordeaux, France
CH du Mans, Service hématologie
🇫🇷Le Mans, France
CH Mulhouse, Service hématologie
🇫🇷Le Mans, France
Klinikum der J.W. Goethe-Universtität Frankfurt, Medizinische Klinik II, Hämatologie/Onkologie
🇩🇪Frankfurt am Main, Germany
Mutterhaus der Borromäerinnen, Medizinische Abteilung
🇩🇪Trier, Germany
Harz-Klinikum Wernigerode-Blankenburg GmbH, Innere Medizin, Hämato-Onkologie und Palliativmedizin
🇩🇪Wernigerode, Germany
Klinikum d. Phillips-Universität, Klinik für Innere Medizin Hämatol./Onkologie/Immunologie
🇩🇪Marburg, Germany
St.-Marien-Hopsital Gem. GmbH
🇩🇪Hamm, Germany
Klinikum Schwäbisch Gmünd, Zentrum Innere Medizin
🇩🇪Mutlangen, Germany
Kliniken Maria Hilf GmbH (Krankenhaus St. Franziskus)
🇩🇪Mönchengladbach, Germany
Diakonieklinikum Stuttgart, Medizinische Klinik II
🇩🇪Stuttgart, Germany
Robert-Bosch-Krankenhaus, Hämatologie/Onkologie
🇩🇪Stuttgart, Germany
Ammerland-Klinik GmbH, Klinik für innere Medizin
🇩🇪Westerstede, Germany
LMU München - Klinikum Großhadern Medizinische Klinik III
🇩🇪München, Germany
Krankenhaus der Barmherzigen Brüder, 1. Medizinische Abteilung
🇩🇪Trier, Germany