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

Lymphoma Clinical Trial

— LYM-2023  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00509379
• Other study ID #: BRIL06
• Secondary ID: LYM-2023
• Status: Completed
• Phase: Phase 2
• First received: July 30, 2007
• Last updated: January 27, 2011
• Start date: September 2006
• Est. completion date: January 2011

Study information

• Verified date: July 2009
• Source: Gruppo Italiano Multiregionale per lo studio dei Linfomi e delle Leucemie
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: January 2011
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Non-Hodgkin Lymphoma

Intervention

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.
• 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.

Locations

Country	Name	City	State
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	Istituto per la ricerca e la cura del cancro	Candiolo	Torino
Italy	Ospedale Civico	Chivasso	Torino
Italy	Stabilimento Ospedaliero	Ciriè	Torino
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	Istituto Clinico Humanitas	Rozzano	Milano
Italy	Spedali Riuniti	Siena
Italy	ASO San Giovanni Battista SC Ematologia 2	Torino
Italy	Ospedale Cardinale Panico	Tricase	Lecce
Italy	Policlinico Universitario	Udine

Sponsors (4)

Lead Sponsor	Collaborator
Gruppo Italiano Multiregionale per lo studio dei Linfomi e delle Leucemie	Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte, Fondazione Italiana Linfomi ONLUS, University of Turin, Italy

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes