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

Sponsor

Gruppo Italiano Multiregionale per lo studio dei Linfomi e delle Leucemie (Other)

Overall Status

Completed

CT.gov ID

NCT00509379

Collaborator

Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte (Other), Fondazione Italiana Linfomi ONLUS (Other), University of Turin, Italy (Other)

Enrollment

Locations

Arm

Duration (Months)

2.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma Non-Hodgkin Lymphoma	Drug: Rituximab Drug: VELCADE	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

48 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Sep 1, 2006

Actual Primary Completion Date :

Nov 1, 2007

Actual Study Completion Date :

Jan 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
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.

Arm

Intervention/Treatment

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.

Outcome Measures

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 [1 year]

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 [4 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.
Age >18-75
Relapse or failure to respond after one or more (maximum three) lines of chemotherapy
Any type of prior chemotherapy, rituximab included. Patients who had received high dose chemotherapy and ASCT can be enrolled into the study
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.
Measurable and/or evaluable disease.
Adequate haematological counts: ANC> 1.0 x 109/L and PLT counts> 75 x 109/L unless due to bone marrow involvement by lymphoma.
Conjugated bilirubin up to 2 x ULN.
Alkaline phosphatase and transaminases up to 2 x ULN.
Creatinine clearances> 30 m/min.
Non peripheral neuropathy or CNS disease.
Life expectancy> 6 months.
Performance status< 2 according to ECOG scale.
Written informed Consent

Exclusion Criteria:

Has known or suspected hypersensitivity or intolerance to rituximab, boron, mannitol, or heparin, if an indwelling catheter is used
History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances
Uncontrolled diabetes (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months before first dose of study drug
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
History of hypotension or has decreased blood pressure (sitting systolic blood pressure SBP 100 mmHg and/or sitting diastolic blood pressure DBP 60 mmHg)
Pregnant or breastfeeding
Peripheral Neuropathy or Neuropathic Pain Grade 2
HIV positivity
HBV positivity with the exception of patients with HBVcAb +, HbsAg -, HBs Ab+/- with HBV-DNA negative
HCV positivity with the exception of patients with no signs of active chronic hepatitis histologically confirmed
Active opportunistic infection
Receipt of extensive radiation therapy, systemic chemotherapy, or other antineoplastic therapy within 4 weeks before enrollment
Exposure to Rituximab within 24 weeks before screening
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.
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

Locations

	Site	City	State	Country
1	Ospedale Cardinale Panico	Tricase	Lecce	Italy
2	Istituto Clinico Humanitas	Rozzano	Milano	Italy
3	Istituto per la ricerca e la cura del cancro	Candiolo	Torino	Italy
4	Ospedale Civico	Chivasso	Torino	Italy
5	Stabilimento Ospedaliero	Ciriè	Torino	Italy
6	ASO SS Antonio e Biagio e Cesare Arrigo	Alessandria		Italy
7	Ospedale Oncologico	Bari		Italy
8	Policlinico S.Orsola Malpighi	Bologna		Italy
9	Spedali Civili	Brescia		Italy
10	Ospedale Armando Businco	Cagliari		Italy
11	ASO S. Croce e Carle	Cuneo		Italy
12	Az. Ospedaliero Universitaria Careggi	Firenze		Italy
13	IRCCS San Raffaele	Milano		Italy
14	Ospedale Cà Granda Niguarda	Milano		Italy
15	Univ. Studi Federico II	Napoli		Italy
16	ASO Maggiore della Carità Ematologia	Novara		Italy
17	Policlinico Monteluce	Perugia		Italy
18	Ospedale Bianchi-Melacrino-Morelli	Reggio Calabria		Italy
19	Università La sapienza Policlinico Umberto I	Roma		Italy
20	Spedali Riuniti	Siena		Italy
21	ASO San Giovanni Battista SC Ematologia 2	Torino		Italy
22	Policlinico Universitario	Udine		Italy