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

Tracking Information
First Submitted Date ICMJE	September 28, 2011
First Posted Date ICMJE	October 10, 2011
Last Update Posted Date	March 7, 2017
Actual Study Start Date ICMJE	May 9, 2009
Estimated Primary Completion Date	December 2018 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: May 4, 2012)	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.
Original Primary Outcome Measures ICMJE; (submitted: October 7, 2011)	Change from Baseline of diseased nodes and nodal masses. [ Time Frame: 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.
Change History	Complete list of historical versions of study NCT01449344 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE	Not Provided
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Efficacy and Safety of R-HAD Alone or in Combination With Bortezomib in Patients With Relapsed or Refractory MCL
Official Title ICMJE	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
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.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Mantle Cell Lymphoma
Intervention ICMJE	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
Study Arms	Experimental: R-HAD + Bortezomib Interventions: Drug: Rituximab Drug: High dose Ara-C Drug: Dexamethasone Drug: Bortezomib; Active Comparator: R-HAD Interventions: Drug: Rituximab Drug: High dose Ara-C Drug: Dexamethasone
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Active, not recruiting
Actual Enrollment ICMJE; (submitted: March 6, 2017)	128
Original Estimated Enrollment ICMJE; (submitted: October 7, 2011)	175
Estimated Study Completion Date	December 2018
Estimated Primary Completion Date	December 2018 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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).
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	France, Germany
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01449344
Other Study ID Numbers ICMJE	MCL2005-01
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Prof. Dr. M. Dreyling (co-chairman), European Mantle Cell Lymphoma Network
Study Sponsor ICMJE	Prof. Dr. M. Dreyling (co-chairman)
Collaborators ICMJE	Klinikum der Universitaet Muenchen, Grosshadern; ClinAssess GmbH; GELARC Service de Pharmacovigilance, Pierre Benite
Investigators ICMJE	Principal Investigator: Martin Dreyling, MD Klinikum der Universität München, Grosshadern
PRS Account	European Mantle Cell Lymphoma Network
Verification Date	March 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP