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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2012 by European Mantle Cell Lymphoma Network
Sponsor:
Collaborators:
Klinikum der Universitaet Muenchen, Grosshadern
ClinAssess GmbH
GELARC Service de Pharmacovigilance, Pierre Benite
Information provided by (Responsible Party):
Dr. M. Dreyling (co-chairman), European Mantle Cell Lymphoma Network
ClinicalTrials.gov Identifier:
NCT01449344
First received: September 28, 2011
Last updated: September 6, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Mantle Cell Lymphoma
Drug: Rituximab
Drug: High dose Ara-C
Drug: Dexamethasone
Drug: Bortezomib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by European Mantle Cell Lymphoma Network:

Primary Outcome Measures:
  • Change from Baseline of diseased nodes and nodal masses. [ Time Frame: approx. 66 and 126 days after start of therapy ] [ Designated as safety issue: Yes ]

    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.



Estimated Enrollment: 175
Study Start Date: November 2011
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: R-HAD + Bortezomib 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
Active Comparator: R-HAD 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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01449344

Contacts
Contact: Martin Dreyling, Professor +49 (89) 7095 ext 2202 Martin.Dreyling@med.uni-muenchen.de

  Show 55 Study Locations
Sponsors and Collaborators
Dr. M. Dreyling (co-chairman)
Klinikum der Universitaet Muenchen, Grosshadern
ClinAssess GmbH
GELARC Service de Pharmacovigilance, Pierre Benite
Investigators
Principal Investigator: Martin Dreyling, MD Klinikum der Universität München, Grosshadern
  More Information

No publications provided

Responsible Party: Dr. M. Dreyling (co-chairman), Coordinating investigator, Germany, European Mantle Cell Lymphoma Network
ClinicalTrials.gov Identifier: NCT01449344     History of Changes
Other Study ID Numbers: MCL2005-01
Study First Received: September 28, 2011
Last Updated: September 6, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by European Mantle Cell Lymphoma Network:
relapsed
refractory

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cytarabine
Rituximab
Bortezomib
Dexamethasone
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents

ClinicalTrials.gov processed this record on August 01, 2014