Non-randomized Safety Study With Bortezomib/Rituximab in Relapsed/Refractory Indolent Lymphoma

NCT ID: NCT00509379

Last Updated: 2011-01-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2011-01-31

Brief Summary

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.

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.

Conditions

Lymphoma; Non-Hodgkin Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

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.

VELCADE

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte

OTHER

Sponsor Role: collaborator

Fondazione Italiana Linfomi - ETS

OTHER

Sponsor Role: collaborator

University of Turin, Italy

OTHER

Sponsor Role: collaborator

Gruppo Italiano Multiregionale per lo studio dei Linfomi e delle Leucemie

OTHER

Sponsor Role: lead

Responsible Party

GIMURELL Onlus

Principal Investigators

Umberto Vitolo, MD

Role: PRINCIPAL_INVESTIGATOR

S.C. Ematologia 2 ASO San Giovanni Battista Torino

Locations

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

Cirié, 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

Florence, , Italy

IRCCS San Raffaele

Milan, , Italy

Ospedale Cà Granda Niguarda

Milan, , 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

Countries

Italy

Other Identifiers

LYM-2023

Identifier Type: -

Identifier Source: secondary_id

BRIL06

Identifier Type: -

Identifier Source: org_study_id