A Phase 3, Open-label, Multicenter, Randomized Study of Sequential Zevalin (Ibritumomab Tiuxetan) Versus Observation in Patients at Least 60 Years of Age With Newly Diagnosed Diffuse Large B-cell Lymphoma in PET-negative Complete Remission After R-CHOP or R-CHOP-like Therapy
1. Patient is 60-years of age or older at time of randomization
2. Histologically confirmed Ann Arbor stage II, III, or IV DLBCL; or FCL Grade 3B
according to the REAL/WHO classification (from initial diagnosis made prior to
starting R-CHOP therapy). Results from a pre R-CHOP marrow shall be available for
3. Local pathology review confirming the DLBCL diagnosis and CD20 positivity, and no
evidence of DLBCL in bone marrow upon confirmation of CR.
4. A paraffin block or original slides available for confirmatory pathology review.
Patients may be randomized based on the local pathology result.
5. Age-adjusted IPI of 1, 2, or 3. The age adjusted IPI is defined by one point for LDH
> upper limit of normal (ULN); Stage III or IV; and Karnofsky performance status <80%
or WHO/ECOG performance status >1.
6. First-line treatment of DLBCL must have been 6 cycles of standard R-CHOP21, R-CHOP14
or DA-EPOCH-R chemotherapy. Patients who received pre-phase therapy for the purpose
of improving performance status prior to initiating R-CHOP are eligible.(See CRF
Manual for further clarification).
7. Complete remission (CR) according to the International Workshop Response Criteria for
NHL described by Cheson et al (Appendix 2). after first-line treatment. 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 chemotherapy. Applicability of the
neck CT means that the patient had involvement of the neck region by palpation /
physical examination at first diagnosis.
8. A negative FDG-PET scan confirming complete response, with negative defined as a
score of 1-3 on the Deauville 5-point scale (Appendix 3) used to quantify
radionucleotide density in PET scans as determined locally (Morschhauser 200735).
9. Bone marrow cellularity greater than 15%, no evidence of myelodysplasia
morphologically and no evidence of involvement with lymphoma either at the pre R-CHOP
marrow or on repeat assessment pre-Zevalin. After completing R-chemotherapy, a repeat
marrow is required for patients randomized to the Zevalin arm only.
10. A WHO/ECOG performance status of 0, 1 or 2.
11. Adequate hematopoietic functions: Absolute neutrophil count (ANC) ≥ 1.0 x 109/L,
Hemoglobin (Hgb) ≥ 9 g/dL, Platelets ≥ 100 x 109/L.
12. Life expectancy of 6 months or longer
13. Written informed consent obtained according to local guidelines
1. Presence of any other malignancy or history of prior malignancy within 5 years of
study entry. Within 5 years, patients treated for Stage I or II cancers are eligible
provided they have a life expectancy of > 5 years (See CRF Manual for clarification).
The 5-year exclusion rule does not apply to-non melanoma skin tumors and in situ
2. Prior radioimmunotherapy, including radiation therapy for NHL, or any other NHL
3. Presence of primary gastric, central nervous system (CNS), or testicular lymphoma at
4. Histological transformation of low-grade NHL.
5. Active hepatitis B or C. (See CRF completion manual)
6. Known history of HIV infection.
7. Abnormal liver function: total bilirubin > 2 × ULN unless secondary to Gilbert
8. Abnormal renal function: serum creatinine > 2.0 × ULN.
9. Non-recovery from the toxic effects of chemotherapy to < grade 2, or interfering with
10. Known hypersensitivity to murine or chimeric antibodies or proteins
11. G-CSF or GM-CSF therapy within 4 weeks prior to Zevalin or observation.
12. Concurrent severe and/or medically uncontrolled 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.
13. Treatment with investigational drugs less than 4 weeks prior to Zevalin or
14. Major surgery less than 4 weeks prior to Zevalin or start of observation.
15. 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. Patients on a chronic dose of prednisone for a
medical condition (e.g. Asthma or autoimmune disease) less than or equal to 20mg
daily, stable for 4 weeks, are permissible.
16. Unwillingness or inability to comply with the protocol.