Phase I/II Trial of Yttrium-90-labeled Daclizumab (Anti-CD25) Radioimmunotherapy With High-dose BEAM Chemotherapy and Autologous Hematopoietic Stem Cell Rescue in Recurrent and Refractory Hodgkin's Lymphoma

Inclusion Criteria

- INCLUSION CRITERIA:

2.1.1.1 All patients must have a pathologically confirmed diagnosis of classical Hodgkin's
lymphoma (HL) as outlined in the WHO Classification System of Lymphoid Tumours. Patients
with nodular lymphocyte-predominant HL (NLPHL) are not eligible.

2.1.1.2 Refractory or relapsed HL patients that are also candidates for ASCT.

2.1.1.3 At least one adverse prognostic factor: (1) initial relapse less than or equal to
12 months after primary chemotherapy, (2) staged as Ann Arbor Classification initial stage
III or IV disease, (3) chemotherapy resistant disease, (4) Failure to achieve a complete
response (CR) with cytoreductive chemotherapy or persistent positive (18)FDGPET imaging.

2.1.1.4 At least 10% of the cells obtained from lymph node, or extranodal sites must react
with anti-CD25 (anti-Tac) on immunofluorescent or immunoperoxidase staining. Because of
the high frequency of CD25 positivity of the infiltrating Tcells in HL tumors, patients
with CD25-positive infiltrating T cells will be eligible even if their Hodgkin's
(Reed-Sternberg) cells are CD25-negative.

2.1.1.5 Measurable disease as defined by the Cheson Response Criteria for Malignant
Lymphoma detailed in section 6.2 with at least one lesion greater than or equal to 1.0 cm
in longest diameter by CT scan.

2.1.1.6 Omission of cytotoxic chemotherapy or other systemic therapy of the malignancy for
greater than or equal to 4 weeks prior to entry into the trial. Patients must be greater
than or equal to 4 weeks since major surgery, radiotherapy, or biotherapy/targeted
therapies and recovered from the toxicity of prior treatment to less than or equal to CTC
grade 1, exclusive of grade 2 alopecia, fatigue, lymphopenia, CD4+ circulating T cells,
WBC or bilirubin.

2.1.1.7 Patients must be greater than or equal to 18-years old.

2.1.1.8 Patients must have a life expectancy of greater than 3 months.

2.1.1.9 Patients must have an ECOG performance status of less than or equal to 1.

2.1.1.10 The patient must have a granulocyte count of at least 1,500/microL and a platelet
count of greater than 100,000/microL.

2.1.1.11 Patients must have a creatinine of less than 2.0 mg/dL, or if the patient has a
serum creatinine greater than or equal to 2.0, a measured creatinine clearance (Ccr) must
be greater than 60 mL/min/1.73m(2).

2.1.1.12 Patients must have a serum alkaline phosphatase, ALT (SGOT), and AST (SGPT) less
than 3 times the upper limit of normal (ULN), unless due to liver or bone involvement by
HL. Under these circumstances, serum alkaline phosphatase, SGPT and SGOT must be less than
5 times ULN.

2.1.1.13 Patients must have a total serum bilirubin less than 2.5 times ULN.

2.1.1.14 Patients must have a cardiac ejection fraction greater than 45% on 2D
echocardiography or MUGA obtained within 28 days of study enrollment.

2.1.1.15 Lung diffusion capacity for carbon monoxide (DLCO) greater than 50%, or forced
expiratory volume at 1.0 seconds (FEV1.0) greater than 65% of predicted on pulmonary
function testing (PFT) obtained within 28 days of study enrollment.

2.1.1.16 Women of childbearing potential must have a negative serum Beta-HCG pregnancy
test at initial screening and within 3 days prior to registration.

2.1.1.17 The effects of (90)Y-daclizumab on the developing human fetus are unknown. Women
of child-bearing potential and men must agree to use adequate contraception (hormonal or
barrier method of birth control; abstinence) prior to study entry, while receiving
treatment and for 4 months after undergoing ASCT. Should a woman become pregnant or
suspect she is pregnant while she or her partner is participating in this study, she
should inform her treating physician immediately.

2.1.1.18 Patients receiving a stable dose (greater than 4 weeks) of corticosteroid therapy
equivalent to 20 mg of prednisone per day or less are eligible.

2.1.1.19 Patients must be able to understand and sign informed consent.

EXCLUSION CRITERIA:

2.1.2.1 Patients enrolled on another therapeutic study.

2.1.2.2 Patients that have received prior radioimmunotherapy.

2.1.2.3 Patients that have received a prior autologous or allogeneic stem cell transplant

2.1.2.4 Patients that have received prior radiation to the lung, excluding prior
mediastinal radiation.

2.1.2.5 Patients with greater than 25% involvement of the bone marrow with HL.

2.1.2.6 Patients with evidence of myelodysplasia, leukemia by morphology, immunostains
flow cytometry or abnormal cytogenetics on a bone- marrow aspirate or biopsy. The
diagnosis of myelodysplasia will be made by an independent investigator of the Laboratory
of Pathology, NCI taking into consideration the totality of the clinical, pathological,
flow cytometric and cytogenetic information described in Appendix E and present in a
particular individual's evaluation.

2.1.2.7 Patients with history of CNS involvement or active CNS involvement by malignancy.

2.1.2.8 Patients with an active second primary cancer will not be eligible. Patients
curatively treated for a second cancer greater than 5 years prior to enrollment without a
recurrence are eligible. Patients curatively treated for a second primary cancer within
the last 5 years with a less than or equal to 5% risk of recurrence are eligible. Patients
with a history of curatively treated basal cell carcinoma or intraepithelial neoplasia of
the uterine cervix will be allowed on study.

2.1.2.9 Patients with serum human anti-human antibody (HAHA) against daclizumab.

2.1.2.10 Patients with HIV infection (antibody positive with positive confirmatory
molecular test).

2.1.2.11 Patients who have chronic hepatitis B or hepatitis C.

2.1.2.12 Patients with an uncontrolled serious infection.

2.1.2.13 Pregnant or breastfeeding women.

2.1.2.14 Patients with significant medical comorbidities, including uncontrolled
hypertension (diastolic BP greater than 115 mmHg), unstable angina, congestive heart
failure (greater than NYHA class II), poorly controlled diabetes, severe chronic pulmonary
disease, coronary angioplasty or myocardial infarction within the last 6 months, or
uncontrolled atrial or ventricular cardiac arrhythmias.

2.1.2.15 Patients with a history of a psychiatric disorder that may interfere with the
understanding and compliance with this protocol and the required follow up.

2.1.2.16 Exclusion at the discretion of the PI or delegate if participation to the study
is deemed too risky (e.g. clinically significant pleural or pericardial effusion or
ascites with possibly increased radio-toxicity).