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

March 6, 2017 updated by: Prof. Dr. M. Dreyling (co-chairman)

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

128

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Argenteuil Cedex, France, 95107
        • CH Victor Dupouy, Service hématologie
      • Bayonne, France, 64109
        • Centre Hospitalier de la côte Basque, Service hématologie
      • Blois, France, 41016
        • CH de Blois, Service hématologie
      • Bordeaux, France, 33076
        • Institut Bergonie, Service Hématologie
      • Corbeil Essonnes, France, 91106
        • CH Sud Francilien de Corbeil, Service hématologie
      • Créteil, France, 94010
        • Hôpital Henri Mondor, Service hématologie
      • Grenoble, France, 38043
        • Hôpital Albert Michallon, Service hématologie
      • Le Mans, France, 68070
        • CH Mulhouse, Service hématologie
      • Le Mans, France, 72015
        • Clinique Victor Hugo, Service hématologie
      • Le Mans, France, 72037
        • CH du Mans, Service hématologie
      • Nice, France, 06202
        • CHU de Nice, Service hématologie
      • Paris, France, 75015
        • CHU Necker, Service d'hématologie - adulte
      • Pessac, France, 33604
        • Hôpital Haut Lévêque, Service Hématologie
      • Pierre Benite, France, 69495
        • CHU Lyon Sud, Service hématologie
      • Poitiers, France, 86021
        • Hôpital Jean Bernard, Service hématologie
      • Pontoise, France, 95301
        • CH René Dubos, Service hématologie
      • Reims, France, 51092
        • CHU Robert Debré, Service hématologie
      • Tours, France, 37044
        • Hôpital Bretonneau, Service hématologie, Bâtiment H. Kaplan
      • Vandoeuvre les Nancy, France, 54511
        • CHU Brabois, Service hématologie
      • Vannes, France, 56017
        • CH de Bretagne Atlantique, Service Hématologie
      • Villejuif, France, 94805
        • Institut Gustave Roussy
  • Germany
      • Altötting, Germany, 84503
        • Kreisklinik Altötting-Burghausen, Sektion Hämatologie/Onkologie und Palliativmedizin
      • Amberg, Germany, 92224
        • Klinikum St. Marien, Med. Klinik II
      • Berlin, Germany, 12351
        • Vivantes Klinikum Neukölln, Medizinische Klinik I - Hämatologie und Onkologie
      • Bottrop, Germany, 46242
        • Knappschaftskrankenhaus, Onkologische Ambulanz
      • Burgwedel, Germany, 30938
        • Praxis für Hämatologie/Onkologie,
      • Düsseldorf, Germany, 40479
        • Marien Hospital Dusseldorf
      • Essen, Germany, 45147
        • Universitätsklinik Essen, Klinik für Hämatologie
      • Frankfurt am Main, Germany, 60590
        • Klinikum der J.W. Goethe-Universtität Frankfurt, Medizinische Klinik II, Hämatologie/Onkologie
      • Greifswald, Germany, 17475
        • Ernst-Moritz-Arndt-Universität, Hämatologie/Onkologie
      • Hagen, Germany, 58095
        • Kath. Krankenhaus Hagen gem. GmbH St.-Marien-Hospital
      • Hamburg, Germany, 20099
        • Asklepios Klinik St. Georg, Abteilung Hämatologie
      • Hamm, Germany, 59071
        • St.-Marien-Hopsital Gem. GmbH
      • Homburg/Saar, Germany, 66421
        • Universitätsklinik des Saarlandes
      • Kaiserslautern, Germany, 67653
        • Westpfalz-Klinikum GmbH, I. Medizinische Klinik
      • Kiel, Germany, 24116
        • UKSH im Städt. Krankenhaus Kiel, II. Med. Klinik und Poliklinik im SSK
      • Köln, Germany, 50924
        • Klinikum der Universität zu Köln, Klinik I f. Innere Medizin
      • Landshut, Germany, 84028
        • Praxis Dr. Vehling-Kaiser
      • Magdeburg, Germany, 39130
        • Klinikum Magdeburg gemeinnützige GmbH, Klinik f. Hämatologie/Onkologie
      • Marburg, Germany, 35033
        • Klinikum d. Phillips-Universität, Klinik für Innere Medizin Hämatol./Onkologie/Immunologie
      • Mutlangen, Germany, 73557
        • Klinikum Schwäbisch Gmünd, Zentrum Innere Medizin
      • Mönchengladbach, Germany, 41063
        • Kliniken Maria Hilf GmbH (Krankenhaus St. Franziskus)
      • München, Germany, 81377
        • LMU München - Klinikum Großhadern Medizinische Klinik III
      • Nürnberg, Germany, 90419
        • Klinikum Nord Nürnberg, 5. Med. Klinik, Onkologie/Hämatologie
      • Oberstaufen, Germany, 87534
        • Schlossberg Klinik, Oberstaufen Internistische Onkologie
      • Siegen, Germany, 57074
        • Diakonie Klinikum Jung Stilling Krankenhaus
      • Stuttgart, Germany, 70176
        • Diakonieklinikum Stuttgart, Medizinische Klinik II
      • Stuttgart, Germany, 70376
        • Robert-Bosch-Krankenhaus, Hämatologie/Onkologie
      • Trier, Germany, 54219
        • Mutterhaus der Borromäerinnen, Medizinische Abteilung
      • Trier, Germany, 54292
        • Krankenhaus der Barmherzigen Brüder, 1. Medizinische Abteilung
      • Ulm, Germany, 89081
        • Universitätsklinikum Ulm, Innere Medizin III
      • Wernigerode, Germany, 38855
        • Harz-Klinikum Wernigerode-Blankenburg GmbH, Innere Medizin, Hämato-Onkologie und Palliativmedizin
      • Westerstede, Germany, 26655
        • Ammerland-Klinik GmbH, Klinik für innere Medizin
      • Zwickau, Germany, 08060
        • Heinrich-Braun-Krankenhaus, Klinik für Innere Medizin III

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: R-HAD + Bortezomib
Drug: Rituximab
Rituximab 375mg/m² IV , day 1
Other Names:
  • 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 Names:
  • Ara-C: Cytarabine
Drug: Dexamethasone
Dexamethasone 40 mg PO, day 1-4
Other Names:
  • Dexamethasone: none
Drug: Bortezomib
Bortezomib 1.5 mg/m² IV, day 1 and 4
Other Names:
  • Bortezomib: Velcade
ACTIVE_COMPARATOR: R-HAD
Drug: Rituximab
Rituximab 375mg/m² IV , day 1
Other Names:
  • 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 Names:
  • Ara-C: Cytarabine
Drug: Dexamethasone
Dexamethasone 40 mg PO, day 1-4
Other Names:
  • Dexamethasone: none

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
approx. 66 and 126 days after start of therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Collaborators

ClinAssess GmbH
Klinikum der Universitaet Muenchen, Grosshadern
GELARC Service de Pharmacovigilance, Pierre Benite

Investigators

  • Principal Investigator: Martin Dreyling, MD, Klinikum der Universität München, Grosshadern

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 9, 2009

Primary Completion (ANTICIPATED)

December 1, 2018

Study Completion (ANTICIPATED)

December 1, 2018

Study Registration Dates

First Submitted

September 28, 2011

First Submitted That Met QC Criteria

October 7, 2011

First Posted (ESTIMATE)

October 10, 2011

Study Record Updates

Last Update Posted (ACTUAL)

March 7, 2017

Last Update Submitted That Met QC Criteria

March 6, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MCL2005-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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