Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies

PRIMARY OBJECTIVES:

I. To estimate the maximally tolerated dose (MTD) of 90Y-BC8-DOTA (anti-cluster of
differentiation [CD]45) (yttrium-90 anti-CD45 monoclonal antibody BC8) that can be delivered
prior to autologous stem cell transplantation for patients with relapsed/refractory B-cell
non-Hodgkin lymphoma (B-NHL), T-cell NHL (T-NHL), and Hodgkin lymphoma (HL).

SECONDARY OBJECTIVES:

I. To optimize the protein dose (antibody [Ab]) to deliver a favorable biodistribution in the
majority of patients.

II. To describe the impact of rituximab concentrations, B-cell depletion, and disease burden
on CD20 and CD45 targeting.

III. To describe response rates and remission durations in relapsed B-NHL, T-NHL, and HL
following administration of myeloablative doses of 90Y-BC8-DOTA prior to autologous stem cell
transplant (ASCT).

IV. To assess the correlation of lymphoma biomarkers with outcomes.

OUTLINE: This is a dose-escalation study of yttrium-90 anti-CD45 monoclonal antibody BC8.

Patients receive indium-111 anti-CD45 monoclonal antibody BC8 intravenously (IV) on day -28
and (if necessary) day -21 to evaluate the antibody's biodistribution. Patients then receive
yttrium-90 anti-CD45 monoclonal antibody BC8 IV on day -14. Patients then undergo autologous
peripheral blood stem cell transplantation on day 0.

After completion of study treatment, patients are followed up at 3, 6, and 12 months and then
annually thereafter.

Inclusion Criteria:

- Patients must have a histologically confirmed diagnosis of B-NHL, T-NHL, or HL; only
patients with classical HL must have documented histologic demonstration of CD45+
cells adjacent to the Reed Sternberg cells; patients must have received at least one
prior standard systemic therapy with documented recurrent or refractory disease;
patients with mantle cell lymphoma (MCL), T-NHL, or other high-risk malignancies may
be enrolled/transplanted in complete remission (CR)/first partial remission (PR1)

- Creatinine < 2.0

- Bilirubin < 1.5 mg/dL

- All patients eligible for therapeutic study must have a minimum of >= 2 x 10^6 CD34/kg
autologous hematopoietic stem cells harvested and cryopreserved

- Patients must have an expected survival of > 60 days and must be free of major
infection

- Patients are preferred to have either a tumor mass amenable to core needle biopsy
during the dosimetry phase, or a measurable tumor mass with at least one site of
involvement measuring 2.5 cm in largest dimension on computed tomography (CT) imaging
for purposes of planar and/or single-photon emission computed tomography (SPECT)/CT
tumor dosimetry

Exclusion Criteria:

- Circulating human anti-mouse antibody (HAMA), to be determined before each infusion

- Systemic anti-lymphoma therapy given in the previous 30 days before the scheduled
therapy dose with the exception of rituximab

- Inability to understand or give an informed consent

- Lymphoma involving the central nervous system

- Other serious medical conditions considered to represent contraindications to ASCT
(e.g., abnormally decreased cardiac ejection fraction, diffusion capacity of the lung
for carbon monoxide [DLCO] < 50% predicted, acquired immune deficiency syndrome
[AIDS], etc.)

- Known human immunodeficiency virus (HIV) seropositivity

- Pregnancy or breast feeding

- Prior allogeneic bone marrow or stem cell transplant

- Prior autologous bone marrow or stem cell transplant within 1 year of enrollment

- Prior radiation therapy (RT) > 20 Gray (Gy) to a critical organ within 1 year of
enrollment

- Southwest Oncology Group (SWOG) performance status >= 2.0

- Patients with relapsed diffuse large B-cell lymphoma (DLBCL) or HL that have achieved
a positron emission tomography (PET)-negative CR following first salvage chemotherapy