Phase II Study of Bexxar in Relapsed/Refractory Diffuse Large Cell Lymphoma

Condition(s) targeted: Lymphoma

Intervention: Tositumomab and iodine I 131 tositumomab (Drug); Tylenol (Drug); Benadryl (Drug); SSKI (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Susan Knox

Official(s) and/or principal investigator(s):
Susan J Knox, Principal Investigator, Affiliation: Stanford University

The purpose of this study is to obtain safety and efficacy data using tositumomab or Bexxar in patients with relapsed/refractory diffuse large cell Non-Hodgkin's lymphoma (DLCL).

Official title: Phase II Study of Bexxar in Relapsed/Refractory Diffuse Large Cell Lymphoma (DLCL)

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

Primary outcome: Response rate and duration of response

Secondary outcome: Time to Progression (TTP), Overall Survival, HAMA incidence, safety and tolerance (including collection of data on late effects)

Detailed description: New treatment modalities are needed for diffuse large cell B cell non-Hodgkin's lymphoma (DLCL). Only 35-40% of patients with DLCL are curable with standard therapy. Therefore, approximately 60-65% of DLCL patients subsequently need salvage therapy. Salvage regimens (e. g. ESHAP, DHAP, (R)-ICE, etc) are very toxic, especially in elderly patients, and have a response rate (RR) of only 45-60% in these patients. The median survival from the time of relapse is less than one year and only a small fraction of such patients benefit from autologous stem cell transplant (ASCT). There is a lack of efficacious treatment options for patients with relapsed/refractory DLCL who are not appropriate candidates for stem cell transplantation. DLCL is a relatively radiosensitive disease and patients with DLCL have been reported to respond to anti-CD20 monoclonal antibody (MAB) therapy. Therefore, radioimmunotherapy targeting CD20 is a rational and promising therapeutic approach for this patient population.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Histologically confirmed DLCL CD20+ B cell NHL who have relapsed after chemotherapy

or are chemotherapy resistant, without prior history of low grade NHL. The patient must have failed at least one chemotherapy regimen containing an anthracycline or equivalent chemotherapeutic agent.

- No anticancer treatment for three weeks prior to the treatment dose of Bexxar (six

weeks if Rituximab, nitrosourea or Mitomycin C), and fully recovered from all toxicities associated with prior surgery, radiation, chemotherapy or immunotherapy

- An IRB approved signed informed consent

- Age greater and or equal to 19 years

- Prestudy Karnofsky Performance Status of >= 70%

- Acceptable laboratory status within 2 weeks prior to patient enrollment including:

- ANC of at least 1,500/mm3, platelet count at least 100,000/mm3, Hct greater than

30% and Hgb greater than 9. 0 gm%

- Bilirubin less than or equal to 2. 0, Creatinine less than or equal to 2. 0

- Bone marrow involvement with lymphoma less than 25% (bilateral bone marrow)

within 6 weeks of enrollment

- Acceptable birth control method for men and women of reproductive potential

- Female patients who are not pregnant or lactating

Exclusion Criteria:

- Prior myeloablative therapies with bone marrow transplantation or peripheral stem

cell rescue

- Patients with impaired bone marrow reserve as indicated by one or more of the

following:

- Platelet count less than 100,000/mm^3

- Hypocellular bone marrow (less than or equal to 15% cellularity)

- Marked reduction in bone marrow precursors of one or more cell lines

- History of failed stem cell collection

- Prior treatment with Fludarabine

- Prior radioimmunotherapy

- Presence of CNS lymphoma

- Patients with HIV or AIDS-related lymphoma

- Patients with evidence of myelodysplasia on bone marrow biopsy

- Patients who have received prior external beam radiation therapy to more than 25% of

active bone marrow

- Patients who have received G-CSF or GM-CSF therapy within 3 weeks prior to treatment

- Pregnant or lactating women

- Presence of HAMA reactivity in patients with prior exposure to murine antibodies or

proteins

- Serious nonmalignant disease or infection, which, in the opinion of the investigator,

would compromise other protocol objectives

- Another primary malignancy (other than squamous cell and basal cell CA of the skin,

in situ CA of the cervix, or treated prostate cancer with stable PSA) for which the patients has not been disease free for at least 3 years

- Major surgery, other than diagnostic surgery, within 4 weeks

- Patients with pleural effusion

Stanford University School of Medicine, Stanford, California 94305, United States

Starting date: September 2004
Last updated: June 19, 2014