PLEASE NOTE: This study has been imported from ClinicalTrials.gov without additional data checks.

PLEASE NOTE: This study has been imported from ClinicalTrials.gov without additional data checks.

Trial Description

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

Trial Acronym (R-HAD)

URL of the trial [---]*

Brief Summary in Lay Language

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.

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.

Brief Summary in Scientific Language

Do you plan to share individual participant data with other researchers?

[---]*

Description IPD sharing plan [---]*

Organizational Data

DRKS-ID: DRKS00010748

Date of Registration in DRKS: 2016/06/29

Date of Registration in Partner Registry or other Primary Registry: 2011/09/28 Investigator Sponsored/Initiated Trial (IST/IIT): yes

Ethics Approval/Approval of the Ethics Committee: [---]*

(leading) Ethics Committee Nr.: [---]*

Primary Registry-ID: NCT01449344 (ClinicalTrials.gov) Sponsor-ID: MCL2005-01 (Dr. M. Dreyling (co-chairman))

Secondary IDs

Free text: Mantle Cell Lymphoma ICD10: C83.1 - Mantle cell lymphoma

Health condition or Problem studied

Arm 1: Drug: Rituximab

Arm 2: Drug: High dose Ara-C Arm 3: Drug: Dexamethasone Arm 4: Drug: Bortezomib

Interventions/Observational Groups

Characteristics

Study Type: Interventional Study Type Non-Interventional: [---]*

Allocation: Randomized controlled trial

Study Type: Interventional Study Type Non-Interventional: [---]*

Allocation: Randomized controlled trial Blinding: [---]*

Control: Active control (effective treament of control group) Purpose: Treatment

Assignment: Parallel Phase: III

Off-label use (Zulassungsüberschreitende Anwendung eines Arzneimittels): [---]*

Who is blinded: [---]*

- 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.

Primary Outcome

Secondary Outcome [---]*

FR France DE Germany

Countries of recruitment

Locations of Recruitment

Kreisklinik Altötting-Burghausen, Sektion Hämatologie/Onkologie und Palliativmedizin, Altötting

Klinikum St. Marien, Med. Klinik II, Amberg

Vivantes Klinikum Neukölln, Medizinische Klinik I - Hämatologie und Onkologie, Berlin

Knappschaftskrankenhaus, Onkologische Ambulanz, Bottrop

Praxis für Hämatologie/Onkologie,, Burgwedel Marien Hospital Düsseldorf, Düsseldorf

Universitätsklinik Essen, Klinik für Hämatologie, Essen

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

Ernst-Moritz-Arndt-Universität, Hämatologie/Onkologie, Greifswald Kath. Krankenhaus Hagen gem. GmbH St.-Marien-Hospital, Hagen Asklepios Klinik St. Georg, Abteilung Hämatologie, Hamburg St.-Marien-Hopsital Gem. GmbH, Hamm

Universitätsklinik des Saarlandes, Homburg/Saar

Westpfalz-Klinikum GmbH, I. Medizinische Klinik, Kaiserslautern

UKSH im Städt. Krankenhaus Kiel, II. Med. Klinik und Poliklinik im SSK, Kiel Klinikum der Universität zu Köl, Klinik I f. Innere Medizin, Köln

Praxis Dr. Vehling-Kaiser, Landshut

Klinikum Magdeburg gemeinnützige GmbH, Klinik f. Hämatologie/Onkologie, Magdeburg

Klinikum Magdeburg gemeinnützige GmbH, Klinik f. Hämatologie/Onkologie, Magdeburg

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

Klinikum Schwäbisch Gmünd, Zentrum Innere Medizin, Mutlangen

Kliniken Maria Hilf GmbH (Krankenhaus St. Franziskus), Mönchengladbach LMU München - Klinikum Großhadern Medizinische Klinik III, München Klinikum Nord Nürnberg, 5. Med. Klinik, Onkologie/Hämatologie, Nürnberg Schlossberg Klinik, Oberstaufen Internistische Onkologie, Oberstaufen Diakonie Klinikum Jung Stilling Krankenhaus, Siegen

Diakonieklinikum Stuttgart, Medizinische Klinik II, Stuttgart Robert-Bosch-Krankenhaus, Hämatologie/Onkologie, Stuttgart Mutterhaus der Borromäerinnen, Medizinische Abteilung, Trier

Krankenhaus der Barmherzigen Brüder, 1. Medizinische Abteilung, Trier Universitätsklinikum Ulm, Innere Medizin III, Ulm

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

Ammerland-Klinik GmbH, Klinik für innere Medizin, Westerstede Heinrich-Braun-Krankenhaus, Klinik für Innere Medizin III, Zwickau

Recruitment

Planned/Actual: [---]*

(Anticipated or Actual) Date of First Enrollment: 2011/11/30 Target Sample Size: 175

Monocenter/Multicenter trial: Multicenter trial National/International: International

Inclusion Criteria

Gender: Both, male and female Minimum Age: 18 Years

Maximum Age: no maximum age

Additional 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).

Dr. M. Dreyling (co-chairman) Telephone: [---]*

Fax: [---]*

E-mail: [---]*

Primary Sponsor

URL: [---]*

Martin Dreyling, MD

Klinikum der Universität München, Grosshadern

Telephone: [---]*

Fax: [---]*

E-mail: [---]*

Contact for Scientific Queries

URL: [---]*

Martin Dreyling, Professor Telephone: +49 (89) 7095 Fax: [---]*

E-mail: Martin.Dreyling at med.uni-muenchen.de Contact for Public Queries

URL: [---]*

Klinikum der Universitaet Muenchen, Grosshadern Telephone: [---]*

Fax: [---]*

E-mail: [---]*

Collaborator, Other Address

Addresses

Klinikum der Universitaet Muenchen, Grosshadern Telephone: [---]*

Fax: [---]*

E-mail: [---]*

Collaborator, Other Address

URL: [---]*

ClinAssess GmbH Telephone: [---]*

Fax: [---]*

E-mail: [---]*

Collaborator, Other Address

URL: [---]*

GELARC Service de Pharmacovigilance, Pierre Benite Telephone: [---]*

Fax: [---]*

E-mail: [---]*

Collaborator, Other Address

URL: [---]*

[---]*

Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor Telephone: [---]*

Fax: [---]*

E-mail: [---]*

URL: [---]*

Sources of Monetary or Material Support

Status

Recruitment Status: Recruiting ongoing Study Closing (LPLV): [---]*

Trial Publications, Results and other documents

Please note:

There are additional attributes available concerning this trial. To open an extended view please click here.

The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs.

- Translation on version: 2

- Last processed date by ClinicalTrials.gov: 2016/06/22