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

This study is currently recruiting participants.
Verified May 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01468311
First received: November 5, 2011
Last updated: March 14, 2014
Last verified: May 2013
  Purpose

Background:

  • Hodgkin s 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 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 Hodgkin s 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....

Condition Intervention Phase
Hodgkin Disease
Hodgkin Lymphoma
Drug: Filgrastim
Drug: Plerixafor
Drug: Yttrium-Daclizumab (CHX-A Daclizumab)
Drug: Carmustine
Drug: Etoposide
Drug: Cytarabine
Drug: Melphalan
Drug: Ca(2+)-DTPA
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Assess safety and adverse events assoc with 90Y-daclizumab radioimmunotherapy (RIT) in combination w/BEAM and ASCT.
  • Determine MTD in mCi of 90Y-daclizumab RIT in combination w/BEAM and ASCT.

Secondary Outcome Measures:
  • Assess the frequency of the failure to engraft, myelodysplastic syndrome (MDS), secondary leukemia.
  • Estimate response rate in patients with refractory or relapsed HD to 90Y-daclizumab RIT in combination w/BEAM and ASCT.

Estimated Enrollment: 95
Study Start Date: October 2011
Estimated Study Completion Date: September 2021
Estimated Primary Completion Date: September 2021 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Filgrastim
    10-16 (Micro)g/kg/d x 5-6 d (Week -6)
    Drug: Plerixafor
    240 ?g/kg on day 5 (and Day 6 if needed)
    Drug: Yttrium-Daclizumab (CHX-A Daclizumab)
    On Day -15: 15 mCi, 5 mCi 5 mg
    Drug: Carmustine
    300 mg/m2 on Day -6
    Drug: Etoposide
    200 mg/m2 on Days -5, -4, -3, -2
    Drug: Cytarabine
    200 mg/m2 on Days -5, -4, -3, -2
    Drug: Melphalan
    140 mg/m2 on Day -1
    Drug: Ca(2+)-DTPA
    250mg/m2 x 3 days on Days -15, -14 and -13
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 who have relapsed from their initial 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, 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 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 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 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.

2.1.2.16 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 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).

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01468311

Contacts
Contact: Tatyana Worthy, R.N. (301) 496-6653 worthyt@mail.nih.gov
Contact: Thomas A Waldmann, M.D. (301) 496-6656 tawald@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    (888) NCI-1937      
Sponsors and Collaborators
Investigators
Principal Investigator: Thomas A Waldmann, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT01468311     History of Changes
Other Study ID Numbers: 120003, 12-C-0003
Study First Received: November 5, 2011
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Immunotherapy
Resistant Hodgkins Lymphoma
Auto Stem Cell Transplant
Combination Chemo and Radiolabeled Monoclonal Antibody
Hodgkin Lymphoma

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Carmustine
Melphalan
Cytarabine
Etoposide
JM 3100
Daclizumab
Lenograstim
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Myeloablative Agonists

ClinicalTrials.gov processed this record on April 20, 2014