Study Comparing Zevalin Regimen With no Further Treatment in Patients With Diffuse Large B-cell Lymphoma.
Condition: Lymphoma, Large Cell, Diffuse
MeSH terms: Lymphoma; Lymphoma, Large B-Cell, Diffuse
Intervention: Zevalin
Intervention description: Zevalin study treatment regimen consisted of 2 rituximab i.v. infusions (Day 1 and Day 7-9) and one [90Y]-ibritumomab tiuxetan infusion in connection with the second rituximab infusion.
The core treatment regimen in the Zevalin arm was:
Day 1: Rituximab i.v. infusion 250 mg/m^2
Day 7-to 9: Rituximab i.v. infusion 250 mg/m^2 immediately followed by [90Y]-ibritumomab tiuxetan 14.8 MBq/kg (0.4 mCi/kg) with a maximum dose of 1184 MBq (32 mCi),administered as slow intravenous push over 10 minutes.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 68.0
Sex: All
Minimum age: 60 Years
Healthy volunteers: No

Summary:

      This study treats patients with diffuse large B-cell lymphoma whose disease is in complete
      remission due to previous treatment with Cyclophosphamide Doxorubicin hydrochloride
      Vincristine Prednisolone- Rituximab (CHOP-R). Half of the patients received Zevalin and the
      other half receive no further anti-cancer treatment. The two patient groups compared to
      determine if Zevalin given after CHOP-R therapy provides greater benefits than receiving no
      additional anti-cancer therapy after CHOP-R.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed, Ann Arbor stage II, III, or IV Diffuse large B-cell lymphoma
             (DLBCL) according to the Revised European American Lymphoma(REAL)/World Health
             Organization (WHO) classification .

          -  Central pathology review confirming the DLBCL diagnosis and Cluster of differentiation
             20 (CD20) positivity, and no evidence of DLBCL in bone marrow

          -  First-line treatment of DLBCL must have been 6 or 8 cycles of standard CHOP
             chemotherapy in combination with rituximab .

          -  Complete remission(CR) or unconfirmed complete remission(CRu) according to the
             International Workshop Response Criteria for Non Hodgkins Lymphoma (NHL) described by
             Cheson et al and modified for this study after first-line treatment with CHOP-R.
             Computerised Tomography (CT) scans of chest, abdomen, pelvis, and neck (if applicable)
             must have been performed within 6 weeks after the last dose of the last course of
             CHOP-R. Applicability of the neck CT means that the patient had involvement of the
             neck region by palpation / physical examination at first diagnosis (pre-CHOP-R).

          -  Central radiographic review of the CT scans from before and after first-line treatment
             with CHOP-R fulfilling the radiological requirements for CR/CRu

          -  Patients 60 years of age or older at time of randomization

          -  WHO performance status (PS) of 0 to 2 within 1 week of randomization

          -  Absolute neutrophil count greater than or equal to 1.5 x 10^9/L within 1 week of
             randomization

          -  Hemoglobin greater than or equal to 10 g/dL within 1 week of randomization

          -  Platelets greater than or equal to 150 x 10^9/L within 1 week of randomization

          -  Life expectancy of 3 months or longer

          -  Written informed consent obtained according to local guidelines

        Exclusion Criteria:

          -  Presence of any other malignancy or history of prior malignancy except non-melanoma
             skin tumors or stage 0 (in situ) cervical carcinoma

          -  Prior radioimmunotherapy, radiation therapy, or any other NHL therapy except
             first-line CHOP-R

          -  Presence of gastric, central nervous system or testicular lymphoma at first diagnosis

          -  Histological transformation of low-grade non-Hodgkin's lymphoma (NHL)

          -  Known seropositivity for hepatitis C virus or hepatitis B surface antigen

          -  Known history of Human Immunodeficiency virus (HIV) infection

          -  Abnormal liver function: total bilirubin > 1.5 x upper limit of normal (ULN) or
             Alanine Aminotransferase > 2.5 x ULN within 1 week of randomization

          -  Abnormal renal function: serum creatinine > 2.0 x ULN within 1 week of randomization

          -  Nonrecovery from the toxic effects of CHOP-R therapy

          -  Known hypersensitivity to murine or chimeric antibodies or proteins

          -  Granulocyte Colony Stimulating Factor (G-CSF) or Granulocyte Macrophage Colony
             Stimulating Factor (GM-CSF) therapy within two weeks (or four weeks if pegylated)
             prior to screening laboratory sampling

          -  Concurrent severe and/or uncontrolled medical disease (e.g., uncontrolled
             diabetes,congestive heart failure, myocardial infarction within 6 months of study,
             unstable and uncontrolled hypertension, chronic renal disease, or active uncontrolled
             infection) which could compromise participation in the study

          -  Male and female patients of child-bearing potential unwilling to practice effective
             contraception during the study and unwilling or unable to continue contraception for
             12 months after their last dose of study treatment

          -  Female patients who are pregnant or are currently breastfeeding

          -  Treatment with investigational drugs less than 4 weeks before the planned Day 1 or
             nonrecovery from the toxic effects of such therapy

          -  Surgery less than 4 weeks before the planned Day 1 or nonrecovery from the side
             effects of such surgery

          -  Concurrent systemic corticosteroid use for any reason except as premedication in case
             of known or suspected allergies to contrast media or as premedication for potential
             side effects of rituximab treatment

          -  Unwillingness or inability to comply with the protocol