Chemotherapy With Monoclonal Antibody and Radioimmunotherapy for High-Risk B-Cell Non-Hodgkins Lymphoma

Experimental: Induction + Consolidation + Bexxar

Induction:Cyclophosphamide, Etoposide, and Rituxan (rituximab) followed by Consolidation: Cytarabine and Doxorubicin followed by radioimmunotherapy: Bexxar (tositumomab)

Droga: cyclophosphamide

1.5g/m2 IV over 1 hour on days 1-4 of induction for a total dose of 6.0g/m2

Otros nombres:

• Cytoxan®

Droga: etoposide

300mg/m2 IV over 1 hour every 12 on days 1-3 of induction for a total dose of 1.8 g/m2.

Otros nombres:

• VP-16

Droga: rituximab

375mg/m2 each week x 4 weeks of induction, beginning on day 1

Otros nombres:

• Rituxan

Droga: cytarabine

3g/m2 IV over 1 hour every 12 during consolidation for a total of 8 doses

Otros nombres:

• Ara-C

Droga: doxorubicin

45mg/m2/day IV over 30 minutes on days 1, 2, 3 during consolidation

Otros nombres:

• Adriamicina

Droga: tositumomab

450mg unlabeled tositumomab over 1 hour, followed by 5 millicurie (mCi) Iodine I-131 labeled tositumomab over 20 minutes on day 0. Therapeutic dose of labeled tositumomab will be administered on day 15.

Otros nombres:

• Bexxar

1 Year Progression-free Survival Rate

Progression-free survival is measured from the first day of induction chemotherapy to the date of progression, relapse or death. Definitions of response criteria are as described by Cheson. Progressive Disease: >50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal node for PDs or nonresponders, appearance of any new lesion during or at the end of therapy.

Disease-free Survival

Disease-free survival is measured from the date of CR or CRu to date of relapse or death

Overall Survival

Overall Survival is measured from the first day of chemotherapy until death from any cause.

Overall Response

Percent of subjects who achieved a complete response (CR) or partial response (PR) any time during the treatment period.

CR = complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy.

PR =

1. >/= 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses.
2. No increase should be observed in the size of other nodes, liver, or spleen.
3. Splenic and hepatic nodules must regress by ≥ 50% in their SPD or, for single nodules, in the greatest transverse diameter.
4. Except splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present.
5. Patients who achieve a CR by the above criteria, but who have persistent morphologic bone marrow involvement will be considered partial responders.
6. No new sites of disease should be observed.

Secondary Malignancies

The number of patients who develop secondary malignancies including solid tumors, acute leukemia and myelodysplasia or other bone marrow failure syndromes.