Rituximab in Children and Adolescents With Relapsed and Refractory B-Cell NHL/L3ALL

Burkitt Lymphoma Clinical Trial

Official title:

A Phase II Study of Mabthera (Rituximab) in Children and Adolescents With Relapsed and Refractory B-Cell NHL/L3ALL

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00180895
• Other study ID #: Rituximab childhood
• Status: Terminated
• Phase: Phase 2
• First received: September 12, 2005
• Last updated: September 7, 2006
• Start date: June 2004

Study information

• Verified date: September 2006
• Source: Gustave Roussy, Cancer Campus, Grand Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

This is a multicentric phase II study of Mabthera (rituximab) in children and adolescents with relapsed and refractory B-cell NHL/L3ALL. The primary objective is to determine the response rate of Rituximab as single agent in relapsed or refractory Burkitt lymphoma, L3 acute leukemia, large B-cell lymphoma and non subclassified aggressive B-cell NHL

Description:

This is a multicentric phase II study of Mabthera (rituximab) in children and adolescents with relapsed and refractory B-cell NHL/L3ALL. The primary objective is to determine the response rate of Rituximab as single agent in relapsed or refractory Burkitt lymphoma, L3 acute leukemia, diffuse large B-cell lymphoma and non subclassified aggressive B-cell NHL. The secondary objectives are to assess the toxicity profile of Rituximab in children and adolescents as single agent, and when followed by chemotherapy, to study pharmacokinetics of Rituximab in serum and in CSF and to determine the overall duration of response, time to progression and survival in patients responders to antiCD20 initially alone and followed by chemotherapy.

Patients will receive Rituximab (Mabthera) at 375 mg/m2, once a week during 4 weeks, administered in IV infusion starting at 50mg/h and increasing by steps of 50 mg/h every 30mn until the speed of 400 mg/h. Patients with combined CNS relapse will receive an intrathecal injection of MTX+HC+Ara-C 48 h after each injection of rituximab First assessment will be done prior to receiving the 3rd course of rituximab. Responding patients (CR, PR) and patients with objective effect (OE) will receive the 3rd and 4th injections of rituximab before starting the salvage chemotherapy (COPADM, CYVE/CC course or ICE, depending on previous chemotherapy regimen received by the patient, followed by HDCT+ hematopoietic stem cell rescue). A second evaluation will be done after the 4th course if performed.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 40
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Months to 20 Years

Eligibility

Inclusion Criteria:

• Histologically or cytologically proven B-cell malignancies, either Burkitt NHL or L3 ALL or large B-cell lymphoma or aggressive B-cell NHL, with the exception of diffuse large B-cell lymphoma arising in the mediastinum.

• Immunohistochemistry showing CD20 positivity

• Measurable (at least one bi-dimensionally measurable lesion) or evaluable (bone marrow, bone involvement) disease in progression since the last evaluation

• First relapsed or refractory disease after LMB or BFM protocol, except the isolated CNS relapses

• Life expectancy > 4 weeks

• Performance status (Karnofsky) > 30

• Adequate hepatic, renal and cardiac functions

• Wash out of 3 weeks in case of recent chemotherapy

• Complete initial work-up within 8 days prior to treatment

• Able to comply with scheduled follow-up and with management of toxicity

• Written inform consent form from adult patients and from parents and legal guardians for minor children

Exclusion Criteria:

• Active viral infection, especially chronic hepatitis B

• previous salvage therapy for relapse

• Prior or current history of severe allergy

• Primary large B-cell lymphoma of the mediastinum

• Isolated CNS relapse

Study Design

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

Related Conditions & MeSH terms

• Burkitt Lymphoma

Intervention

Drug:
• Rituximab

Locations

Country	Name	City	State
France	Institut Gustave Roussy	Villejuif

Sponsors (2)

Lead Sponsor	Collaborator
Gustave Roussy, Cancer Campus, Grand Paris	Hoffmann-La Roche

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of patients achieving at least objective response after 2 courses of rituximab
Secondary	Rate of objective response after 4 courses of rituximab
Secondary	Rate of initially responding patients who progressed during the second phase of treatment
Secondary	Toxicity
Secondary	Pharmacokinetic evaluation in serum and CSF