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Zevalin Twice in Aggressive Non-Hodgkin Lymphoma

Primary Purpose

Diffuse Large B-Cell Lymphoma

Status

Terminated

Phase

Phase 2

Locations

Italy

Study Type

Interventional

Intervention

90Y-Ibritumomab Tiuxetan

About this trial

This is an interventional treatment trial for Diffuse Large B-Cell Lymphoma focused on measuring two sequential doses of 90Y-Ibritumomab Tiuxetan

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age 18-75
Diagnosis of CD20+ B-diffuse large cell de novo or transformed or follicular lymphoma grade IIIb
Stage II, III, IV according to Ann Arbor criteria
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
Performance status 0-2 according to WHO criteria
HIV negativity
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
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.
Neutrophils count ³ 1.5 x 109/l, Haemoglobin ³ 9 g/dl, Platelets ³ 100 x 109/l before second Zevalin infusion
Use of effective contraception for the entire treatment period in patients sexually active
Negative pregnancy test in child bearing potential women
Life expectancy > 6 months
Written informed consent

Exclusion Criteria:

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

Sites / Locations

Divisione di Ematologia Ospedale SS Antonio e Biagio
Istituto di Ematologia e Oncologia Medica L. Seragnoli Policlinco S. Orsola
Divisione di Ematologia, Spedali Civili
Divisione di Ematologia Ospedale Centrale di Bolzano
Divisione di Ematologia Ospedale Businco
Divisione di Ematologia Ospedale Cardinale Panico
Divisione di Ematologia Ospedale Niguarda Cà Granda
Divisione di Oncoematologia IRCC
Divisione di Ematologia Istituto Nazionale Fondazione Pascale
SC Ematologia Ospedale Maggiore Università Avogadro
Divisione di Oncoematologia Azienda Ospedalier S. Maria
SCDO Ematologia 2 AOU San Giovanni Battista

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

90Y-Ibritumomab Tiuxetan double dose

Arm Description

90Y-Ibritumomab Tiuxetan administered at 0.4 mCi/kg at phase 2 and then at 0.2 mCi/kg at phase 3

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT00902525

First Posted

May 14, 2009

Last Updated

December 28, 2012

Sponsor

Gruppo Italiano Multiregionale per lo studio dei Linfomi e delle Leucemie

Collaborators

Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte

1. Study Identification

Unique Protocol Identification Number

NCT00902525

Brief Title

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

2. Study Status

Record Verification Date

December 2012

Overall Recruitment Status

Terminated

Why Stopped

After enrolling 25 patients an interim analysis was done.The study was discontinued in the absence of the minimum number of 6 patients free of events

Study Start Date

January 2008 (undefined)

Primary Completion Date

January 2009 (Actual)

Study Completion Date

September 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Gruppo Italiano Multiregionale per lo studio dei Linfomi e delle Leucemie

Collaborators

Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diffuse Large B-Cell Lymphoma

Keywords

two sequential doses of 90Y-Ibritumomab Tiuxetan

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Arm Title

90Y-Ibritumomab Tiuxetan double dose

Arm Type

Experimental

Arm Description

90Y-Ibritumomab Tiuxetan administered at 0.4 mCi/kg at phase 2 and then at 0.2 mCi/kg at phase 3

Intervention Type

Drug

Intervention Name(s)

90Y-Ibritumomab Tiuxetan

Intervention Description

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

Primary Outcome Measure Information:

Title

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.

Time Frame

after the enrolment of the 15th patient

Secondary Outcome Measure Information:

Title

Time Frame

after the enrolment of the 23rd patient

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age 18-75 Diagnosis of CD20+ B-diffuse large cell de novo or transformed or follicular lymphoma grade IIIb Stage II, III, IV according to Ann Arbor criteria 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 Performance status 0-2 according to WHO criteria HIV negativity 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 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. Neutrophils count ³ 1.5 x 109/l, Haemoglobin ³ 9 g/dl, Platelets ³ 100 x 109/l before second Zevalin infusion Use of effective contraception for the entire treatment period in patients sexually active Negative pregnancy test in child bearing potential women Life expectancy > 6 months Written informed consent Exclusion Criteria: More than two lines of prior chemotherapy before study entry Prior high dose chemotherapy and autologous stem cell transplantation HIV positivity HBV positivity with the exception of patients with HBVcAb +, HbsAg -, HBs Ab+/- with HBV-DNA negative HCV positivity with the exception of patients with no signs of active chronic hepatitis histologically confirmed History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances Uncontrolled diabetes (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months before first dose of study drug 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 Pregnant or breastfeeding CNS lymphoma involvement. History of malignant carcinoma within the last 3 years other than squamous cell and basal cell carcinoma. Cardiac failure with VEF < 40% Clinical evidence of not controlled infections

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Barbara Botto, MD

Organizational Affiliation

SCDO Ematologia AOU San Giovanni Battista Torino

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Umberto Vitolo, MD

Organizational Affiliation

SCDO Ematologia 2 AOU San Giovanni Battista Torino

Official's Role

Principal Investigator

Facility Information:

Facility Name

Divisione di Ematologia Ospedale SS Antonio e Biagio

City

Alessandria

State/Province

ZIP/Postal Code

15100

Country

Italy

Facility Name

Istituto di Ematologia e Oncologia Medica L. Seragnoli Policlinco S. Orsola

City

Bologna

State/Province

ZIP/Postal Code

40138

Country

Italy

Facility Name

Divisione di Ematologia, Spedali Civili

City

Brescia

State/Province

ZIP/Postal Code

25100

Country

Italy

Facility Name

Divisione di Ematologia Ospedale Centrale di Bolzano

City

Bolzano

State/Province

ZIP/Postal Code

39100

Country

Italy

Facility Name

Divisione di Ematologia Ospedale Businco

City

Cagliari

State/Province

ZIP/Postal Code

09100

Country

Italy

Facility Name

Divisione di Ematologia Ospedale Cardinale Panico

City

Tricase

State/Province

ZIP/Postal Code

73039

Country

Italy

Facility Name

Divisione di Ematologia Ospedale Niguarda Cà Granda

City

Milano

State/Province

ZIP/Postal Code

20162

Country

Italy

Facility Name

Divisione di Oncoematologia IRCC

City

Candiolo

State/Province

ZIP/Postal Code

10060

Country

Italy

Facility Name

Divisione di Ematologia Istituto Nazionale Fondazione Pascale

City

Napoli

ZIP/Postal Code

80131

Country

Italy

Facility Name

SC Ematologia Ospedale Maggiore Università Avogadro

City

Novara

ZIP/Postal Code

28100

Country

Italy

Facility Name

Divisione di Oncoematologia Azienda Ospedalier S. Maria

City

Terni

ZIP/Postal Code

05100

Country

Italy

Facility Name

SCDO Ematologia 2 AOU San Giovanni Battista

City

Turin

ZIP/Postal Code

10126

Country

Italy

12. IPD Sharing Statement

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Zevalin Twice in Aggressive Non-Hodgkin Lymphoma

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