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

NCT ID: NCT01449344

Last Updated: 2017-03-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

128 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-05-09

Study Completion Date

2018-12-31

Brief Summary

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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

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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.

Conditions

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Mantle Cell Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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R-HAD + Bortezomib

Group Type EXPERIMENTAL

Rituximab

Intervention Type DRUG

Rituximab 375mg/m² IV , day 1

High dose Ara-C

Intervention Type DRUG

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

Dexamethasone

Intervention Type DRUG

Dexamethasone 40 mg PO, day 1-4

Bortezomib

Intervention Type DRUG

Bortezomib 1.5 mg/m² IV, day 1 and 4

R-HAD

Group Type ACTIVE_COMPARATOR

Rituximab

Intervention Type DRUG

Rituximab 375mg/m² IV , day 1

High dose Ara-C

Intervention Type DRUG

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

Dexamethasone

Intervention Type DRUG

Dexamethasone 40 mg PO, day 1-4

Interventions

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Rituximab

Rituximab 375mg/m² IV , day 1

Intervention Type 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

Intervention Type DRUG

Dexamethasone

Dexamethasone 40 mg PO, day 1-4

Intervention Type DRUG

Bortezomib

Bortezomib 1.5 mg/m² IV, day 1 and 4

Intervention Type DRUG

Other Intervention Names

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Rituximab:Rituxan Ara-C: Cytarabine Dexamethasone: none Bortezomib: Velcade

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Klinikum der Universitaet Muenchen, Grosshadern

OTHER

Sponsor Role collaborator

ClinAssess GmbH

INDUSTRY

Sponsor Role collaborator

GELARC Service de Pharmacovigilance, Pierre Benite

UNKNOWN

Sponsor Role collaborator

Prof. Dr. M. Dreyling (co-chairman)

OTHER

Sponsor Role lead

Responsible Party

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Prof. Dr. M. Dreyling (co-chairman)

Coordinating investigator, Germany

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Martin Dreyling, MD

Role: PRINCIPAL_INVESTIGATOR

Klinikum der Universität München, Grosshadern

Locations

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CH Victor Dupouy, Service hématologie

Argenteuil, , France

Site Status

Centre Hospitalier de la côte Basque, Service hématologie

Bayonne, , France

Site Status

CH de Blois, Service hématologie

Blois, , France

Site Status

Institut Bergonie, Service Hématologie

Bordeaux, , France

Site Status

CH Sud Francilien de Corbeil, Service hématologie

Corbeil-Essonnes, , France

Site Status

Hôpital Henri Mondor, Service hématologie

Créteil, , France

Site Status

Hôpital Albert Michallon, Service hématologie

Grenoble, , France

Site Status

CH Mulhouse, Service hématologie

Le Mans, , France

Site Status

Clinique Victor Hugo, Service hématologie

Le Mans, , France

Site Status

CH du Mans, Service hématologie

Le Mans, , France

Site Status

CHU de Nice, Service hématologie

Nice, , France

Site Status

CHU Necker, Service d'hématologie - adulte

Paris, , France

Site Status

Hôpital Haut Lévêque, Service hématologie

Pessac, , France

Site Status

CHU Lyon Sud, Service hématologie

Pierre-Bénite, , France

Site Status

Hôpital Jean Bernard, Service hématologie

Poitiers, , France

Site Status

CH René Dubos, Service hématologie

Pontoise, , France

Site Status

CHU Robert Debré, Service hématologie

Reims, , France

Site Status

Hôpital Bretonneau, Service hématologie, Bâtiment H. Kaplan

Tours, , France

Site Status

CHU Brabois, Service hématologie

Vandœuvre-lès-Nancy, , France

Site Status

CH de Bretagne Atlantique, Service Hématologie

Vannes, , France

Site Status

Institut Gustave ROUSSY

Villejuif, , France

Site Status

Kreisklinik Altötting-Burghausen, Sektion Hämatologie/Onkologie und Palliativmedizin

Altötting, , Germany

Site Status

Klinikum St. Marien, Med. Klinik II

Amberg, , Germany

Site Status

Vivantes Klinikum Neukölln, Medizinische Klinik I - Hämatologie und Onkologie

Berlin, , Germany

Site Status

Knappschaftskrankenhaus, Onkologische Ambulanz

Bottrop, , Germany

Site Status

Praxis für Hämatologie/Onkologie,

Burgwedel, , Germany

Site Status

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

Cologne, , Germany

Site Status

Marien Hospital Düsseldorf

Düsseldorf, , Germany

Site Status

Universitätsklinik Essen, Klinik für Hämatologie

Essen, , Germany

Site Status

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

Frankfurt am Main, , Germany

Site Status

Ernst-Moritz-Arndt-Universität, Hämatologie/Onkologie

Greifswald, , Germany

Site Status

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

Hagen, , Germany

Site Status

Asklepios Klinik St. Georg, Abteilung Hämatologie

Hamburg, , Germany

Site Status

St.-Marien-Hopsital Gem. GmbH

Hamm, , Germany

Site Status

Universitätsklinik des Saarlandes

Homburg/Saar, , Germany

Site Status

Westpfalz-Klinikum GmbH, I. Medizinische Klinik

Kaiserslautern, , Germany

Site Status

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

Kiel, , Germany

Site Status

Praxis Dr. Vehling-Kaiser

Landshut, , Germany

Site Status

Klinikum Magdeburg gemeinnützige GmbH, Klinik f. Hämatologie/Onkologie

Magdeburg, , Germany

Site Status

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

Marburg, , Germany

Site Status

Kliniken Maria Hilf GmbH (Krankenhaus St. Franziskus)

Mönchengladbach, , Germany

Site Status

Klinikum Schwäbisch Gmünd, Zentrum Innere Medizin

Mutlangen, , Germany

Site Status

LMU München - Klinikum Großhadern Medizinische Klinik III

München, , Germany

Site Status

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

Nuremberg, , Germany

Site Status

Schlossberg Klinik, Oberstaufen Internistische Onkologie

Oberstaufen, , Germany

Site Status

Diakonie Klinikum Jung Stilling Krankenhaus

Siegen, , Germany

Site Status

Diakonieklinikum Stuttgart, Medizinische Klinik II

Stuttgart, , Germany

Site Status

Robert-Bosch-Krankenhaus, Hämatologie/Onkologie

Stuttgart, , Germany

Site Status

Mutterhaus der Borromäerinnen, Medizinische Abteilung

Trier, , Germany

Site Status

Krankenhaus der Barmherzigen Brüder, 1. Medizinische Abteilung

Trier, , Germany

Site Status

Universitätsklinikum Ulm, Innere Medizin III

Ulm, , Germany

Site Status

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

Wernigerode, , Germany

Site Status

Ammerland-Klinik GmbH, Klinik für innere Medizin

Westerstede, , Germany

Site Status

Heinrich-Braun-Krankenhaus, Klinik für Innere Medizin III

Zwickau, , Germany

Site Status

Countries

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France Germany

References

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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.

Reference Type DERIVED
PMID: 38678093 (View on PubMed)

Other Identifiers

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MCL2005-01

Identifier Type: -

Identifier Source: org_study_id

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