Phase II study on the feasibility and efficacy of R-DHAP + HD-MTX, combined with intrathecal rituximab, followed by autologous stem cell transplantation in patients with a recurrent aggressive B-cell lymphoma with CNS localisation - HOVON 80 NH

• Conditions: relapsed B cell lymphoma; MedDRA version: 8.1Level: LLTClassification code 10029547Term: Non-Hodgkin's lymphoma

• Registration Number: EUCTR2006-002141-37-NL
• Lead Sponsor: HOVON foundation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-07-05
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

*Diagnosis of aggressive malignant B-cell lymphoma based upon a representative histology specimen according to the WHO classification (see appendix A):
-Follicular lymphoma grade III
-Diffuse large B-cell lymphoma
Prior low-grade” lymphoma with histologically proven transformation to follicular lymphoma grade III or DLBCL is also permitted.
*CD 20 positive
*First progression or relapse with CNS localisation (see below) without or with systemic relapse (preferably histologically proven). ‘Progressive’ includes patients who have progressive disease (PD), without prior response and patients who have progression after first PR.
*Diagnosis of CNS localisation based on at least one of the following:
-Unequivocal morphological and/or immunophenotypical evidence of CSF lymphoma
-clinical AND MRI evidence of leptomeningeal localisation
-brain parenchymal lesion showing homogeneous contrast enhancement suspect for lymphoma, concurrently with systemic progression or recurrence
-biopsy-proven brain parenchymal NHL localisation of previously diagnosed systemic NHL
*Age 18-65 years inclusive
*WHO performance status 0 – 2 (see appendix F) with or without administration of steroids
*Witnessed written informed consent according to the centre’s requirements
*Negative pregnancy test in women of reproductive potential

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

*History of intolerance of exogenous protein administration
*Severe cardiac dysfunction (NYHA classification III-IV, appendix G, or LVEF < 45%)
*Severe pulmonary dysfunction (vital capacity or diffusion capacity < 50% of predicted value) unless clearly related to NHL involvement
*Hepatic dysfunction, bilirubin or transaminase = 2.5 x upper normal limit, unless related to lymphoma.
*Renal dysfunction (serum creatinine =150 umol/l or clearance = 60 ml/min)
*Prior cranial radiotherapy
*Active uncontrolled infection
*Known HIV-positivity
*(EBV) post-transplant lymphoproliferative disorder
*Documented CNS involvement during 1st line therapy (MTX intrathecal profylaxis during 1st line therapy is no exclusion criterium)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess in a multicenter phase II study of patients with a recurrent or progressive B-cell lymphoma with CNS involvement:<br>The progression-free survival after R-DHAP-MTX + rituximab intrathecally followed by myelo-ablative chemotherapy and autologous peripheral blood stem cell transplantation.<br>;Secondary Objective: -The response rate after R-DHAP-MTX + rituximab intrathecally<br>-The overall survival after R-DHAP-MTX + rituximab intrathecally followed by myelo-ablative chemotherapy and autologous peripheral blood stem cell transplantation <br>-To evaluate the toxicity of R-DHAP-MTX + rituximab intrathecally followed by myelo-ablative chemotherapy and autologous peripheral blood stem cell transplantation<br>;Primary end point(s): See appendix B for a complete definition of endpoints.<br>Primary endpoint<br>Progression-free survival measured from the date of registration. Patients still alive or lost to follow up are censored at the last day they were known to be alive.<br><br>