Non-randomized Safety Study With Bortezomib/Rituximab in Relapsed/Refractory Indolent Lymphoma (LYM-2023)

This study has been completed.
Sponsor:
Collaborators:
Epidemiologia e prevenzione Oncologica (CPO)in Piemonte
Fondazione Italiana Linfomi ONLUS
University of Turin, Italy
Information provided by:
Gruppo Italiano Multiregionale per lo studio dei Linfomi e delle Leucemie
ClinicalTrials.gov Identifier:
NCT00509379
First received: July 30, 2007
Last updated: January 27, 2011
Last verified: July 2009
  Purpose

The promising activity of Bortezomib as single agent in low grade lymphoma patients in small studies has led to a number of larger multicenter trials with Bortezomib in combination with Rituximab in mantle-cell lymphoma, follicular lymphoma and marginal zone lymphoma.


Condition Intervention Phase
Lymphoma
Non-Hodgkin Lymphoma
Drug: Rituximab
Drug: VELCADE
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Multicenter Non-randomized Study to Assess Safety, Toxicity and Clinical Activity of the Association of Bortezomib(VELCADE)With Rituximab in Relapsed/Refractory Indolent Non Follicular and Mantle-cell Non-Hodgkin Lymphoma

Resource links provided by NLM:


Further study details as provided by Gruppo Italiano Multiregionale per lo studio dei Linfomi e delle Leucemie:

Primary Outcome Measures:
  • To demonstrate a statistical benefit in overall response rate (ORR) of the Bortezomib/Rituximab association in this study 3/13 or fewer responses are observed during the first stage then the trail is stopped early [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • If 12/43 or fewer responses are observed by the end of the trail, then no further investigation of this regimen is warranted [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]

Enrollment: 48
Study Start Date: September 2006
Study Completion Date: January 2011
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
All patients will be treated with six courses of therapy with a thirteen day rest period between them. Courses will be restarted at day 36.
Drug: Rituximab
Rituximab 375 mg/m2 as slow iv infusion day 1-8-15-22.Patients will be treated with six courses of therapy with a thirteen day rest period between them. Courses will be restarted at day 36.
Drug: VELCADE
VELCADE 1,6 mg/m2 iv bolus days 1-8-15-22 (Velcade will be administrated prior of Rituximab infusion).Patients will be treated with six courses of therapy with a thirteen day rest period between them. Courses will be restarted at day 36.

Detailed Description:

This is a open label, non randomized, phase II , multicenter, prospective trial to evaluate the efficacy and safety of the combination of bortezomib and rituximab in patients with relapsed or refractory rituximab naïve or sensitive indolent non-follicular and mantle cell non-Hodgkin's lymphoma. Despite of the availability of treatment for this disease, this study is justified because no known therapies are really curative and it is necessary to look for new treatment options to improve the clinical outcome and prognosis of relapsed indolent lymphoma. This study is designed for patients not eligible for high-dose chemotherapy and autologous stem cells transplantation.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with naïve or sensitive rituximab indolent non-follicular and mantle cell non-Hodgkin's Lymphoma disease that had failed to respond or relapsed after primary therapy. There is a demonstrated progressive disease requiring further treatment. Histological subtype included into the study are are as follows Small lymphocytic/lymphoplasmocytic lymphoma; Nodal marginal zone Lymphoma (MALT lymphoma are excluded) Splenic marginal zone lymphoma Mantle cell lymphoma A lymphnode biopsy is advisable if it is not harmful for the patients, before enrollment of the patient into the study in order to confirm diagnosis and to rule out histologic transformation. Lymphnode biopsy should be performed within 6 months before study entry.
  2. Age >18-75
  3. Relapse or failure to respond after one or more (maximum three) lines of chemotherapy
  4. Any type of prior chemotherapy, rituximab included. Patients who had received high dose chemotherapy and ASCT can be enrolled into the study
  5. Naïve or sensitive rituximab disease. If the patient received Rituximab, he/she must have responded and the TTP from the last dose to rituximab must have been 6 months or more.
  6. Measurable and/or evaluable disease.
  7. Adequate haematological counts: ANC> 1.0 x 109/L and PLT counts> 75 x 109/L unless due to bone marrow involvement by lymphoma.
  8. Conjugated bilirubin up to 2 x ULN.
  9. Alkaline phosphatase and transaminases up to 2 x ULN.
  10. Creatinine clearances> 30 m/min.
  11. Non peripheral neuropathy or CNS disease.
  12. Life expectancy> 6 months.
  13. Performance status< 2 according to ECOG scale.
  14. Written informed Consent

Exclusion Criteria:

  1. Has known or suspected hypersensitivity or intolerance to rituximab, boron, mannitol, or heparin, if an indwelling catheter is used
  2. History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances
  3. Uncontrolled diabetes (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months before first dose of study drug
  4. Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure (Attachment 5, NYHA Classification of Cardiac Disease), uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis
  5. History of hypotension or has decreased blood pressure (sitting systolic blood pressure SBP 100 mmHg and/or sitting diastolic blood pressure DBP 60 mmHg)
  6. Pregnant or breastfeeding
  7. Peripheral Neuropathy or Neuropathic Pain Grade 2
  8. HIV positivity
  9. HBV positivity with the exception of patients with HBVcAb +, HbsAg -, HBs Ab+/- with HBV-DNA negative
  10. HCV positivity with the exception of patients with no signs of active chronic hepatitis histologically confirmed
  11. Active opportunistic infection
  12. Receipt of extensive radiation therapy, systemic chemotherapy, or other antineoplastic therapy within 4 weeks before enrollment
  13. Exposure to Rituximab within 24 weeks before screening
  14. Have received an experimental drug or used an experimental medical device within 4 weeks before the planned start of treatment. Concurrent participation in non-treatment studies is allowed, if it will not interfere with participation in this study.
  15. Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00509379

Locations
Italy
Ospedale Cardinale Panico
Tricase, Lecce, Italy
Istituto Clinico Humanitas
Rozzano, Milano, Italy
Istituto per la ricerca e la cura del cancro
Candiolo, Torino, Italy
Ospedale Civico
Chivasso, Torino, Italy
Stabilimento Ospedaliero
Ciriè, Torino, Italy
ASO SS Antonio e Biagio e Cesare Arrigo
Alessandria, Italy
Ospedale Oncologico
Bari, Italy
Policlinico S.Orsola Malpighi
Bologna, Italy
Spedali Civili
Brescia, Italy
Ospedale Armando Businco
Cagliari, Italy
ASO S. Croce e Carle
Cuneo, Italy
Az. Ospedaliero Universitaria Careggi
Firenze, Italy
IRCCS San Raffaele
Milano, Italy
Ospedale Cà Granda Niguarda
Milano, Italy
Univ. Studi Federico II
Napoli, Italy
ASO Maggiore della Carità Ematologia
Novara, Italy
Policlinico Monteluce
Perugia, Italy
Ospedale Bianchi-Melacrino-Morelli
Reggio Calabria, Italy
Università La sapienza Policlinico Umberto I
Roma, Italy
Spedali Riuniti
Siena, Italy
ASO San Giovanni Battista SC Ematologia 2
Torino, Italy
Policlinico Universitario
Udine, Italy
Sponsors and Collaborators
Gruppo Italiano Multiregionale per lo studio dei Linfomi e delle Leucemie
Epidemiologia e prevenzione Oncologica (CPO)in Piemonte
Fondazione Italiana Linfomi ONLUS
University of Turin, Italy
Investigators
Principal Investigator: Umberto Vitolo, MD S.C. Ematologia 2 ASO San Giovanni Battista Torino
  More Information

No publications provided

Responsible Party: Dr. Umberto Vitolo, GIMURELL Onlus
ClinicalTrials.gov Identifier: NCT00509379     History of Changes
Other Study ID Numbers: BRIL06, LYM-2023
Study First Received: July 30, 2007
Last Updated: January 27, 2011
Health Authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Keywords provided by Gruppo Italiano Multiregionale per lo studio dei Linfomi e delle Leucemie:
Relapsed/refractory indolent lymphoma
Non-follicular Lymphoma
Mantle cell non-Hodgkin Lymphoma
Patients naïve or sensitive to rituximab
Patients not eligible for high dose chemotherapy with ASCT

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Bortezomib
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014