Main info

Identifier:

HOVON 85 NHL

Sponsor:

HOVON

Working group party:

Lymphoma

Age:

>= 18

Stage:

2nd Line

Echelon:

Level C-HIC&C-SCT

Included patients:

64

(of 60)

Active sites:

27

(of 20)

Title:

Phase II study on the feasibility and efficacy of consolidation with 90^Y-ibritumomab tiuxetan in patients with relapsed or refractory aggressive B-cell non-Hodgkin’s lymphoma having achieved partial or complete remission after induction with R-PECC chemotherapy.

Timeline

News

Flow

Details

Phase:

Select:

Monitoring Type:

Not any more

Objectives:

Primary objective:

• Assessment of the feasibility of this treatment approach. Measured primarily by the percentage of patients that reach CR or PR after R-PECC and proceed to 90Y-ibritumomab tiuxetan treatment, and by the fraction of patients that endure the 90Y-ibritumomab tiuxetan treatment without major problems, i.e. the safety and tolerability of 90Y-ibritumomab tiuxetan after R-PECC chemotherapy.

Secondary objectives:

• Efficacy of the 90Y-ibritumomab tiuxetan treatment, measured by the fraction of PR PET positive patients who become PET negative after 90Y-ibritumomab tiuxetan treatment and by the failure free survival and overall survival measured from the start of 90Y-ibritumomab tiuxetan.
• Assessment of the results of the whole treatment approach in terms of the overall response rate, duration of response, failure free survival and overall survival from start of R-PECC treatment.

Eligibility

Inclusion Criteria:

Inclusion criteria R-PECC induction

• Histologically confirmed aggressive B-cell NHL according to the World Health Organization (WHO) classification (see appendix A):
• Follicular lymphoma grade 3b
• Diffuse large B-cell lymphoma
• Refractory disease or histologically confirmed first or second relapse (Refractory is defined as no response or partial remission according to CT. Patients in partial response (PR) can only be included in case of positive PET scan or positive biopsy)
• CD20 positive (assessed at 1st diagnosis or from fresh histology at confirmation of relapse or immunophenotyping of circulating CD20-positive NHL cells from peripheral blood)
• Current measurable disease, i.e. measurable in two perpendicular dimensions on physical examination or computerized tomography (CT) scan using standardized response criteria for NHL (Cheson et al21, 1999) (see appendix B)
• Age > 18 years
• WHO performance status 0, 1 or 2 (see appendix E)
• Life expectancy of at least 3 months
• Absolute neutrophil count > 1.5 x 10^9/l and platelet count > 100 x 10^9/l (unless caused by NHL infiltration in the bone marrow)
• Written informed consent

Inclusion criteria 90Y-ibritumomab tiuxetan consolidation:

• Patients with PR or CR after 4 cycles of R-PECC
• Less than 25% bone marrow involvement (confirmed by bone marrow biopsy of at least 1.5 cm, if initially positive)
• WHO performance status 0, 1, or 2
• Time interval since the start of the 4th R-PECC between 6 and 12 weeks
• No rituximab-related adverse event necessitating stopping of rituximab administration

Exclusion Criteria:

Exclusion criteria R-PECC induction

• Prior allogeneic stem cell transplantation
• Prior radioimmunotherapy
• Patients who have received chemotherapy or radiotherapy within 6 weeks prior to study entry or who have not recovered from toxicities related to prior therapies
• Eligibility for ASCT
• ASCT within 12 months of study entry
• Investigational drugs within 4 weeks prior to entry on this study or persistent toxic side effects of such therapy
• Treatment with external-beam radiation therapy to more than 25% of active bone marrow (see appendix F)
• A history of intolerance to rituximab
• Severe cardiac, pulmonary, neurological, psychiatric or metabolic disease which could compromise participation in the study, or serious underlying medical conditions which could impair the ability of the patient to participate in the trial
• Hepatic dysfunction, bilirubin or transaminases ≥ 2.5 x upper normal limit (unless caused by the NHL)
• Renal dysfunction, serum creatinine ≥ 180 µmol/l or clearance ≤ 40 ml/min (unless caused by the NHL)
• Active uncontrolled infections
• Patients known to be HIV-positive
• Current or chronic hepatitis B or hepatitis C infection
• Symptomatic NHL localization in the central nervous system (CNS). Lumbal puncture is not required unless CNS involvement with NHL is clinically suspected
• Transformed indolent lymphoma
• Post-transplant lymphoproliferative disorder
• Pregnant or breast-feeding female patients. Negative serum pregnancy test at study is mandatory for female patients of childbearing potential

Exclusion criteria 90Y-ibritumomab tiuxetan consolidation. All exclusion criteria for R-PECC induction, plus the following:

• Extensive pleural effusion or ascites
• Impaired bone marrow reserve, as indicated by one or more of the following:
  • Absolute neutrophil count < 1.5 x 10^9/l, platelet count < 100 x 10^9/l, Hemoglobin < 5.0 mmol/l
  • Hypoplastic bone marrow at biopsy
• Administration of systemic corticosteroids at doses higher than 20 mg/day prednisolone or equivalent 2 weeks prior to 90Y-ibritumomab tiuxetan administration.

Registration Details

Participating Sites

= Active hospitals

= Inactive hospitals