Clinical trial NCT00902525: Zevalin Twice in Aggressive Non-Hodgkin Lymphoma
Official title: Two Repeated Doses of Yttrium-90 Ibritumomab Tiuxetan (Zevalin®) as Salvage Treatment for Patients With Relapsed or Refractory Aggressive B-cell Lymphoma: a Phase II Study.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Diffuse Large B-Cell Lymphoma
Keywords: two sequential doses of 90Y-Ibritumomab Tiuxetan
Lead sponsor: Gruppo Italiano Multiregionale per lo studio dei Linfomi e delle Leucemie
Sponsor class: OTHER
Collaborators: name: Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte
First posted: 2009-05-15
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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 aggressive lymphoma. This study is designed for patients not eligible for high-dose chemotherapy and autologous stem cells transplantation.

Detailed description: The objectives of this study are to evaluate the efficacy and safety of two sequential doses of 90Y-Ibritumomab Tiuxetan administered after salvage chemotherapy in patients with relapsed/refractory aggressive lymphoma non-eligible for HDC and ASCT.

Eligibility criteria: Inclusion Criteria:

1. Age 18-75
2. Diagnosis of CD20+ B-diffuse large cell de novo or transformed or follicular lymphoma grade IIIb
3. Stage II, III, IV according to Ann Arbor criteria
4. Chemoresistant disease after first line treatment (CHOP-like + Rituximab) or relapsed patients after one or two lines of chemotherapy not-eligible for high dose chemotherapy and autologous stem cell transplantation
5. Performance status 0-2 according to WHO criteria
6. HIV negativity
7. Normal liver, lung and kidney function: conjugated bilirubin up to 2 x ULN, alkaline phosphatase and transaminases up to 2 x ULN, creatinine clearances ≥45 ml/min
8. Neutrophils count ³ 1.5 x 109/l, Haemoglobin ³ 9 g/dl, Platelets ³ 150 x 109/l and bone marrow involvement \< 25% before first Zevalin infusion.
9. Neutrophils count ³ 1.5 x 109/l, Haemoglobin ³ 9 g/dl, Platelets ³ 100 x 109/l before second Zevalin infusion
10. Use of effective contraception for the entire treatment period in patients sexually active
11. Negative pregnancy test in child bearing potential women
12. Life expectancy \> 6 months
13. Written informed consent

Exclusion Criteria:

1. More than two lines of prior chemotherapy before study entry
2. Prior high dose chemotherapy and autologous stem cell transplantation
3. HIV positivity
4. HBV positivity with the exception of patients with HBVcAb +, HbsAg -, HBs Ab+/- with HBV-DNA negative
5. HCV positivity with the exception of patients with no signs of active chronic hepatitis histologically confirmed
6. History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances
7. Uncontrolled diabetes (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months before first dose of study drug
8. 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
9. Pregnant or breastfeeding
10. CNS lymphoma involvement.
11. History of malignant carcinoma within the last 3 years other than squamous cell and basal cell carcinoma.
12. Cardiac failure with VEF \< 40%
13. Clinical evidence of not controlled infections

Primary outcomes:
measure: An interim analysis on all the available data after the enrolment of the 15th patient (completion of the 1st stage) will be conducted, both for safety and efficacy.
timeFrame: after the enrolment of the 15th patient
Secondary outcomes:
measure: after the interim analysis, the writing committee of the study will evaluate to increase the second dose of Zevalin to 0.3 mCi/Kg. The same procedure will be applied to decide if the trial must be stopped after the enrolment of the 23rd patient.
timeFrame: after the enrolment of the 23rd patient
Other outcomes:
Locations:
city: Alessandria
country: Italy
facility: Divisione di Ematologia Ospedale SS Antonio e Biagio
state: AL
city: Bologna
country: Italy
facility: Istituto di Ematologia e Oncologia Medica L. Seragnoli Policlinco S. Orsola
state: BO
city: Brescia
country: Italy
facility: Divisione di Ematologia, Spedali Civili
state: BS
city: Bolzano
country: Italy
facility: Divisione di Ematologia Ospedale Centrale di Bolzano
state: BZ
city: Cagliari
country: Italy
facility: Divisione di Ematologia Ospedale Businco
state: CA
city: Tricase
country: Italy
facility: Divisione di Ematologia Ospedale Cardinale Panico
state: LE
city: Milano
country: Italy
facility: Divisione di Ematologia Ospedale Niguarda Cà Granda
state: MI
city: Candiolo
country: Italy
facility: Divisione di Oncoematologia IRCC
state: TO
city: Napoli
country: Italy
facility: Divisione di Ematologia Istituto Nazionale Fondazione Pascale
city: Novara
country: Italy
facility: SC Ematologia Ospedale Maggiore Università Avogadro
city: Terni
country: Italy
facility: Divisione di Oncoematologia Azienda Ospedalier S. Maria
city: Turin
country: Italy
facility: SCDO Ematologia 2 AOU San Giovanni Battista
Study officials:
affiliation: SCDO Ematologia AOU San Giovanni Battista Torino
name: Barbara Botto, MD
role: STUDY_DIRECTOR
affiliation: SCDO Ematologia 2 AOU San Giovanni Battista Torino
name: Umberto Vitolo, MD
role: PRINCIPAL_INVESTIGATOR
References: