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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01449344
Recruitment Status : Unknown
Verified March 2017 by Prof. Dr. M. Dreyling (co-chairman), European Mantle Cell Lymphoma Network.
Recruitment status was:  Active, not recruiting
First Posted : October 10, 2011
Last Update Posted : March 7, 2017
Sponsor:
Collaborators:
Klinikum der Universitaet Muenchen, Grosshadern
ClinAssess GmbH
GELARC Service de Pharmacovigilance, Pierre Benite
Information provided by (Responsible Party):
Prof. Dr. M. Dreyling (co-chairman), European Mantle Cell Lymphoma Network

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
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures 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  ICMJE 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  ICMJE
  • 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 Unknown status
Actual Enrollment  ICMJE
 (submitted: March 6, 2017)
128
Original Estimated Enrollment  ICMJE
 (submitted: October 7, 2011)
175
Estimated Study Completion Date  ICMJE 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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE 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  ICMJE 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