Yttrium Y 90 Basiliximab and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With Mature T-cell Non-Hodgkin Lymphoma

PRIMARY OBJECTIVES:

I. To determine if administration of 90Y-basiliximab/DOTA (yttrium Y 90 basiliximab), when
given in combination with standard dose BEAM, as conditioning for autologous hematopoietic
cell transplant (AHCT), is safe, by evaluation of toxicities, including type, frequency,
severity, attribution, time course and duration.

II. To determine the maximum tolerated dose (MTD) of 90Y-basiliximab/DOTA when given in
combination with standard dose BEAM, in patients with T-cell non-Hodgkin lymphoma (T-NHL) as
part of conditioning for AHCT.

SECONDARY OBJECTIVES:

I. To characterize and evaluate hematologic recovery in terms of neutrophil and platelet
engraftment time.

II. To estimate radiation doses to the whole body and normal organs through serial imaging
studies.

III. To estimate overall survival, progression-free survival, non-relapse mortality and
cumulative incidence of relapse/progression at 100-days (non-relapse mortality [NRM] only),
1-year and 2-years.

OUTLINE: This is a dose-escalation study of yttrium Y 90 basiliximab.

Patients receive yttrium Y 90 basiliximab intravenously (IV) on days -21 and -14, carmustine
IV over 1-2 hours on days -7 and -6, cytarabine IV twice daily (BID) on days -5 to -2,
etoposide IV BID on days -5 to -2, and melphalan IV on day -1. Patients undergo autologous
hematopoietic stem cell transplant on day 0.

After completion of study treatment, patients are followed up at 30, 100, and 180 days and 1,
1.5, and 2 years.

Inclusion Criteria:

- Patients with a pathologically confirmed diagnosis of systemic mature T-cell
non-Hodgkin lymphoma (NHL) with City of Hope pathology review as per World Health
Organization (WHO) classification of lymphomas 2008, who are deemed eligible for high
dose therapy and AHCT including patients in:

* T-NHL histologies including peripheral T-cell lymphomas (PTCLs), cutaneous T-cell
lymphomas (CTCLs) and natural killer (NK)/T cell lymphomas

- First remission after initial first-line therapy (CR1) in PTCL patients, except
for anaplastic lymphoma receptor tyrosine kinase (ALK)+ anaplastic large cell
lymphoma (ALCL) and CTCL; patients with minimal residual disease after induction
therapy may also be eligible at the discretion of the principal investigator (PI)

- Relapsed/refractory disease, stable disease, partial remission (PR) or complete
remission (CR), who have received at least 2 lines of therapy, and do not have an
adequate allogenetic stem cell transplant option

- Life expectancy >= 6 months

- Karnofsky status >= 70%

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control or abstinence) prior to study entry and
for six months following duration of study participation; should a woman become
pregnant or suspect that she is pregnant while participating on the trial, she should
inform her treating physician immediately

- Cardiac ejection fraction of >= 50% by echocardiogram or multi gated acquisition scan
(MUGA)

- Forced expiratory volume in one second (FEV1) > 65% of predicted measured, or
diffusing capacity of the lung for carbon monoxide (DLCO) > 50% of predicted measured

- Bilirubin < 1.5 x normal except in cases where abnormal liver function tests (LFTS)
are due to involvement with T-NHL

- Serum glutamic oxaloacetic transaminase (SGOT) AND serum glutamate pyruvate
transaminase (SGPT) < 2 x normal except in cases where abnormal LFTS are due to
involvement with T-NHL

- Serum creatinine of < 1.5 mg/dL, and a measured creatinine clearance of > 60 mL/min

- Patients will be enrolled at collection of at least 3.0 x 10^6 CD34 cells/kg of
autologous hematopoietic progenitor cells (HPC-A) by apheresis; a minimum of 2
collection procedures is required, unless collection on day # 1 > 5.0 x 10^6, CD34
cells/kg; a maximum of 10 collections is allowed; bone marrow harvest to supplement
apheresis is not allowed

- Recovery from non-hematologic toxicities of salvage cytoreductive chemotherapy to =<
grade 2 (Common Terminology Criteria for Adverse Events [CTCAE] version 4 [v4])

- Body mass index (BMI) > 35% will be considered on a case-by-case basis by the
Radiation Oncology principal investigator (P.I.)

- All subjects must have the ability to understand and the willingness to sign a written
informed consent

- Systemic chemotherapy or radiation cannot have been given within 4 weeks prior to the
Y-90 dose of radioimmunotherapy (RIT), with the exception of single agent
cyclophosphamide priming chemotherapy administered for mobilization

Exclusion Criteria:

- Progressive disease

- Patients should not have any uncontrolled illness including ongoing or active
infection requiring therapy

- Patients may not be receiving any other investigational agents, or concurrent
biological, chemotherapy, or radiation therapy; may have received an experimental
agent prior to enrolling in the trial

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to basiliximab

- Pregnant women are excluded from this study; breastfeeding should be discontinued if
the mother is treated with indium In 111 (111In-) and 90Y-basiliximab-DOTA

- Prior high dose chemotherapy for autologous hematopoietic cell transplantation or
prior allogeneic transplantation

- Significant prior external beam dose-limiting radiation to a critical organ based on
review of the prior radiation treatment records by the Radiation Oncology PI; patients
who have had prior external beam radiation > 2000 cGy (at 180 to 200 cGy per day) to
the lung will be ineligible; patients with ANY prior radiation to the heart are
ineligible; patients with > 500 cGy to the kidney will be excluded from the study;
Note: patients who have had electron beam therapy are still eligible and will be
evaluated on a case by case basis by the Radiation Oncology PI

- Presence of antibody against basiliximab in serum (only required for patients who have
received prior antibody)

- Research participants with presence of other active malignancy; however, research
participants with history of prior malignancy treated with curative intent and in
complete remission are eligible; any history of myelodysplasia is excluded

- Active hepatitis B or C viral infection or hepatitis B surface antigen positive

- Patients with a detectable human immunodeficiency virus (HIV) viral load or who are
HIV-positive AND have a resistant genotype

- Patients with psychosocial circumstances or illnesses that preclude protocol
participation (to be determined by P.I.)

- Any cytogenetic abnormality in the bone marrow that is known to be associated with or
predictive of myelodysplasia is excluded; this includes, but is not limited to,
del(5), del(7), del(11)

- Evidence of marrow disease by flow and morphology after upfront or salvage
cytoreductive therapy and before stem cell mobilization

- Bone marrow (BM) harvest required to reach adequate cell dose for transplant

- Subjects, who in the opinion of the investigator, may not be able to comply with the
safety monitoring requirements of the study