Zevalin Twice in Aggressive Non-Hodgkin Lymphoma

Diffuse Large B-Cell Lymphoma Clinical Trial

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00902525
• Other study ID #: ZETAL07
• Status: Terminated
• Phase: Phase 2
• First received: May 14, 2009
• Last updated: December 28, 2012
• Start date: January 2008
• Est. completion date: September 2011

Study information

• Verified date: December 2012
• Source: Gruppo Italiano Multiregionale per lo studio dei Linfomi e delle Leucemie
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 25
• Est. completion date: September 2011
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Diffuse Large B-Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• 90Y-Ibritumomab Tiuxetan
All patients receive 2 courses of age-adjusted R-miniDHAP followed by two doses of 90Y-Ibritumomab Tiuxetan

Locations

Country	Name	City	State
Italy	Divisione di Ematologia Ospedale SS Antonio e Biagio	Alessandria	AL
Italy	Istituto di Ematologia e Oncologia Medica L. Seragnoli Policlinco S. Orsola	Bologna	BO
Italy	Divisione di Ematologia Ospedale Centrale di Bolzano	Bolzano	BZ
Italy	Divisione di Ematologia, Spedali Civili	Brescia	BS
Italy	Divisione di Ematologia Ospedale Businco	Cagliari	CA
Italy	Divisione di Oncoematologia IRCC	Candiolo	TO
Italy	Divisione di Ematologia Ospedale Niguarda Cà Granda	Milano	MI
Italy	Divisione di Ematologia Istituto Nazionale Fondazione Pascale	Napoli
Italy	SC Ematologia Ospedale Maggiore Università Avogadro	Novara
Italy	Divisione di Oncoematologia Azienda Ospedalier S. Maria	Terni
Italy	Divisione di Ematologia Ospedale Cardinale Panico	Tricase	LE
Italy	SCDO Ematologia 2 AOU San Giovanni Battista	Turin

Sponsors (2)

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

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		after the enrolment of the 15th patient	Yes
Secondary	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.		after the enrolment of the 23rd patient	Yes