Yttrium Y 90 Ibritumomab Tiuxetan, Rituximab, Indium In-111 Ibritumomab Tiuxetan, Fludarabine, Melphalan, and Donor Stem Cell Transplant in Treating Patients With B-Cell Non-Hodgkin Lymphoma

PRIMARY OBJECTIVES: I. To evaluate the safety and efficacy of a preparative regimen of
Yttrium-90 (90^Y)- labeled anti-cluster of differentiation (CD)20 monoclonal antibody (MAb)
(yttrium Y 90 ibritumomab tiuxetan) in combination with fludarabine (fludarabine phosphate)
and melphalan followed by allogeneic hematopoietic stem cell transplant (APBSCT) for
treatment of patients with B-cell low-grade non-Hodgkin lymphoma (LG NHL), intermediate-grade
non-Hodgkin lymphoma (IG NHL) and mantle cell lymphoma (MCL). II. To evaluate the short- and
long-term complications of this new preparative regimen, including rates of engraftment,
acute and chronic graft-versus-host-disease (GVHD) and infectious complications. III. To
estimate the disease response rate, disease relapse (progression) rate, and non-relapse
mortality rate. IV. To perform exploratory studies that seek to measure/characterize the
expression of costimulatory molecules and impact of these molecules on the natural killer
(NK) and T cells of a subset of lymphoma patients pre- post- allogeneic stem cell transplant
(ASCT) and the stem cell product from a portion of sibling donors.

OUTLINE: REDUCED-INTENSITY CONDITIONING: Patients receive rituximab intravenously (IV)
followed by indium In-111 ibritumomab tiuxetan IV over 10 minutes on day -21 and rituximab IV
followed by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day -14. Patients also
receive fludarabine phosphate IV on days -9 to -5 and melphalan IV on day -4.

STEM CELL TRANSPLANTATION: Patients undergo APBSCT on day 0.

GVHD PROPHYLAXIS: Patients receive tacrolimus IV or orally (PO) and sirolimus PO beginning on
day -3 and continuing for up to 6 months with taper.

After completion of study treatment, patients are followed up every 3 months for 1 year and
then every 6 months for up to 5 years.

Inclusion Criteria:

- 6/6/human leukocyte antigen (HLA) matched sibling donor or related donor, or
acceptable matched unrelated donor

- Biopsy (Bx) proven diagnosis of LG (including small lymphocytic lymphoma [SLL]/chronic
lymphocytic leukemia [CLL], lymphoplasmacytic lymphoma, marginal zone,
mucosa-associated lymphoid tissue [MALT] lymphoma and follicular lymphoma [FL] grade 1
and 2), IG (FL grade 3 and DLCL) or MCL NHL

- Prior demonstrated monoclonal CD20+ malignant B-Cell population in lymph nodes and/or
BM Bx specimen

- LG NHL; must have relapsed after achieving a complete response (CR) or partial
response (PR) to prior therapy or have never responded to prior therapy, including
chemotherapy and/or MAb therapy

- MCL NHL in any disease state

- Other aggressive B-cell lymphomas (excluding Burkitt lymphoma or Burkitt-like
lymphoma) having had at least one relapse or having been refractory to chemotherapy

- Bone marrow (BM) aspiration and Bx ( =< 42 days prior to imaging dose) which show <
25% lymphomatous involvement of total cellularity; in CLL, peripheral lymphocyte count
< 5000/mm^3

- Salvage chemotherapy/MAbs to reduce BM lymphomatous involvement and reduce disease
bulk allowed

- Normal renal function test with serum creatinine of =< 1.5 mg/dl, or a creatinine
clearance of >= 60 ml/min

- Adequate pulmonary function as measured by forced expiratory volume in one second
(FEV1) > 65% of predicted measured, or a diffusing capacity of carbon monoxide (DLCO)
>= 50% of predicted measured

- Cardiac Ejection fraction of > 50% by Echocardiogram (ECHO) or multi gated acquisition
(MUGA)

- Adequate liver function tests with a bilirubin of =< 1.5 x normal and serum glutamic
oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) =< 2 x
normal

- Negative Human Immunodeficiency Virus (HIV) antibody

- Karnofsky Performance Status (KPS) > 80

- No active Central Nervous System (CNS) disease or prior history of CNS disease

- Involved field External Beam Therapy (EBT) to area excluding lung, heat, liver, and
kidney allowed, but evaluated on a case-by-case basis

- Recovery from last therapy and therapy dose (Y-90 Zevalin) must be >= 4 weeks from
prior systemic chemotherapy

- DONOR: Age < 75 years

- DONOR: HLA genotypically identical related donor or acceptable matched unrelated donor

- DONOR: Must consent to G-CSF administration and leukapheresis for matched sibling
donor, but for unrelated donor, the donor will sign a standard consent for donation at
their designated donor or collection center

- DONOR: Must have adequate veins for leukapheresis or agree to placement of a Central
Venous Catheter (CVC [femoral, subclavian])

Exclusion Criteria:

- Presence of Human Anti-Zevalin Antibody (HAZA)

- Prior radioimmunotherapy (RIT)

- Prior AHSCT; but prior aHSCT is allowed; prior fractionated total body irradiation
(FTBI) in the conditioning regimen will be evaluated on an individual basis

- Prior malignancy, except for: adequately treated basal cell or squamous cell skin
cancer; adequately treated noninvasive carcinomas; or other cancer from which the
patient has been disease-free for at least 5 years; myelodysplastic syndromes (MDS) is
excluded from this criterion

- Active evidence of Hepatitis B or C infection; hepatitis B surface antigen positive

- Total peripheral lymphocyte count > 5,000/mm^3 if SLL/CLL

- Burkitt lymphoma or Burkitt-like lymphoma

- DONOR: Age < 12 years

- DONOR: Identical twin

- DONOR: Pregnancy

- DONOR: HIV infection

- DONOR: Inability to achieve adequate venous access

- DONOR: Known allergy to G-CSF

- DONOR: Current serious systemic illness or any disease that may preclude the use of
G-CSF (eg, recent thromboembolic event); for unrelated donors, considered ineligible
by National Marrow Donor Program (NMDP) donor evaluation center