Yttrium-90-labeled Daclizumab With Chemotherapy and Stem Cell Transplant for Hodgkin's Lymphoma

• Status: Terminated
• Trial end date: 2020-10-22
• Target enrollment: 0
• Participant gender: All

Summary

Background:

• Hodgkins lymphoma (HL) is a highly treatable cancer. However, if HL does not respond to chemotherapy or returns after chemotherapy, further treatments often are not successful.

• Some HL cells have a molecule called cluster of differentiation 25 (CD25) on the surface. Daclizumab is a drug that can detect CD25 on cells. In a treatment study for HL that did not respond to chemotherapy, daclizumab plus a radioactive atom called Yttrium 90 helped kill these HL cells. Researchers want to combine this 90Y daclizumab with high-dose chemotherapy and stem cell transplant. This treatment may be more effective than the daclizumab alone.

Objectives:

• To see if yttrium-90 daclizumab, high-dose chemotherapy, and stem cell transplants can treat HL that has not responded to earlier treatments.

Eligibility:

• Individuals at least 18 years of age who have Hodgkins lymphoma that has not responded to chemotherapy.

Design:

• Participants will be screened with a physical exam and medical history. They will also have blood and urine tests.

• Participants will have filgrastim and plerixafor to move stem cells into the blood. Stem cells will be collected with apheresis.

• Four weeks after stem cells are collected, participants will have the 90Y daclizumab and normal daclizumab to treat the HL. Chemotherapy will start 9 days after the first treatment.

• Most participants will have a second dose of 90Y daclizumab 6 weeks after the first dose.

• After each daclizumab treatment, participants will have several imaging studies of the chest and abdomen. Blood samples will also be collected.

• On the day after the last day of chemotherapy, participants will receive the stem cells collected earlier. Filgrastim injections will help stimulate stem cell growth....

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Daclizumab; Immunoglobulin G

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 World Health Organization (WHO) Classification System of Lymphoid Tumours. Patients with nodular lymphocyte-predominant Hodgkin's lymphoma (HL) (NLPHL) are not eligible.

2.1.1.2 Refractory or relapsed HL patients that are also candidates for auto stem cell transplant (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) fluorodeoxyglucose positron emission tomography (FDGPET) imaging.

2.1.1.4 At least 10% of the cells obtained from lymph node, or extranodal sites must react with anti-cluster of differentiation 25 (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 computed tomography (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, cluster of differentiation 4 (CD4)+ circulating T cells, white blood cell (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 Eastern Cooperative Oncology Group (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, alanine aminotransferase (ALT) serum glutamic oxaloacetic transaminase (SGOT), and aspartate aminotransferase (AST) serum glutamic pyruvic transaminase (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 multi-gated acquisition scan (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-human chorionic gonadotropin (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 who have relapsed from their initial Adriamycin, bleomycin, vinblastine, dacarbazine) ABVD or similar standard treatment regimen and have not received any other chemotherapy or salvage systemic treatment.

2.1.2.2 Patients that have received prior radioimmunotherapy.

2.1.2.2. Patients enrolled on another therapeutic study.

2.1.2.3 Patients that have received prior radioimmunotherapy.

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

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

radiation.

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

2.1.2.7 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, National Cancer Institute (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.

2.1.2.8 Patients with history of central nervous system (CNS) involvement or active CNS involvement by malignancy.

2.1.2.9 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.

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

2.1.2.11 Patients with human immunodeficiency virus (HIV) infection (antibody positive with positive confirmatory molecular test).

2.1.2.2 Patients who have chronic hepatitis B or hepatitis C.

2.1.2.13 Patients with an uncontrolled serious infection.

2.1.2.14 Pregnant or breastfeeding women.

2.1.2.15 Patients with significant medical comorbidities, including uncontrolled hypertension (diastolic blood pressure (BP) greater than 115 mmHg), unstable angina, congestive heart failure (greater than New York Heart Association (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.

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

2.1.2.17 Exclusion at the discretion of the principal investigator (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).