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

NCT01468311 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 12000312-C-0003
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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....

Conditions

Hodgkin Disease; Hodgkin Lymphoma

Keywords

Immunotherapy; Resistant Hodgkins Lymphoma; Auto Stem Cell Transplant; Combination Chemo and Radiolabeled Monoclonal Antibody; Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose (MTD) of 90Y-daclizumab With Carmustine, Etoposide, Cytarabine, [Ara-C, Cytosine Arabinoside] and Melphalan (BEAM) and Auto Stem Cell Transplant (ASCT): Phase I Portion

  The MTD is defined as the dose level below the dose at which 2 out of 2 to 6 patients at a given dose level develop dose limiting toxicity (DLT). A DLT is defined as patients who develop either a Common Terminology Criteria in Adverse Events (CTCAE) v4.0 grade 3 or greater non-hematologic toxicity, with the exception of fatigue, of more than 5 days duration possibly, probably or definitely related to the infusion of 90Y-daclizumab prior to the start of BEAM chemotherapy (Day - 6) will have developed by definition a dose-limiting toxicity (DLT).

  Day 100 post autologous stem cell transplant

• Number of Participants With Adverse Events

  Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

  30 months

• Number of Participants With A Dose Limiting Toxicity

  Patients who develop either a Common Terminology Criteria in Adverse Events (CTCAE) v4.0 grade 3 or greater non-hematologic toxicity, with the exception of fatigue, of more than 5 days duration possibly, probably or definitely related to the infusion of 90Y-daclizumab prior to the start of Carmustine, Etoposide, Cytarabine, \[Ara-C, Cytosine Arabinoside\] and Melphalan (BEAM) chemotherapy (Day - 6) will have developed by definition a dose-limiting toxicity (DLT).

  30 months

Secondary Outcomes (4)

• Overall Response Rate

  Response is evaluated at day 100 post autologous stem cell transplant, then 1-4 times yearly for 5 years

• Complete Response Rate

  20 months post autologous stem cell transplant

• Disease Free Survival (DFS)

  DFS is evaluated at day 100 post autologous stem cell transplant, then 1-4 times yearly for 5 years

• Overall Survival

  OS is evaluated at day 100 post autologous stem cell transplant, then 1-4 times yearly for 5 years

Study Arms (1)

Yttrium-90-labeled Daclizumab + Chemotherapy

EXPERIMENTAL

Yttrium-90-labeled Daclizumab + BCNU, etoposide, cytarabine and melphalan (BEAM) + Auto stem cell transplant (ASCT)

Procedure: Auto stem cell transplant; Drug: BEAM; Radiation: 111In-daclizumab; Radiation: 90Y-daclizumab

Interventions

Auto stem cell transplant PROCEDURE

Auto stem cell transplant (ASCT) is given after 90Y-daclizumab

Yttrium-90-labeled Daclizumab + Chemotherapy

BEAM DRUG

BCNU, etoposide, cytarabine and melphalan (BEAM) chemotherapy are given after 90Y-daclizumab

Yttrium-90-labeled Daclizumab + Chemotherapy

111In-daclizumab RADIATION

111In-daclizumab will be administered to patients with each therapeutic infusion of 90Y-daclizumab in order to define the distribution of radiolabeled daclizumab, and to allow visualization by scans.

Yttrium-90-labeled Daclizumab + Chemotherapy

90Y-daclizumab RADIATION

90Y-daclizumab administered with a fixed dose of pentetate calcium trisodium (Ca-DTPA) followed by BEAM Chemo and Auto stem cell transplant

Yttrium-90-labeled Daclizumab + Chemotherapy

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Refractory or relapsed HL patients that are also candidates for auto stem cell transplant (ASCT).
• 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.
• 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.
• 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.
• 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.
• Patients must be greater than or equal to 18-years old.
• Patients must have a life expectancy of greater than 3 months.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 1.
• The patient must have a granulocyte count of at least 1,500/microL and a platelet count of greater than 100,000/microL.
• 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).
• 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.
• Patients must have a total serum bilirubin less than 2.5 times ULN.
• 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.
• 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.

You may not qualify if:

• 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.
• Patients that have received prior radioimmunotherapy.
• Patients enrolled on another therapeutic study.
• Patients that have received prior radioimmunotherapy.
• Patients that have received a prior autologous or allogeneic stem cell transplant
• Patients that have received prior radiation to the lung, excluding prior mediastinal
• radiation.
• Patients with greater than 25% involvement of the bone marrow with HL.
• 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.
• Patients with history of central nervous system (CNS) involvement or active CNS involvement by malignancy.
• 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.
• Patients with serum human anti-human antibody (HAHA) against daclizumab.
• Patients with human immunodeficiency virus (HIV) infection (antibody positive with positive confirmatory molecular test).
• Patients who have chronic hepatitis B or hepatitis C.
• Patients with an uncontrolled serious infection.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Canellos GP, Anderson JR, Propert KJ, Nissen N, Cooper MR, Henderson ES, Green MR, Gottlieb A, Peterson BA. Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med. 1992 Nov 19;327(21):1478-84. doi: 10.1056/NEJM199211193272102.

  PMID: 1383821 BACKGROUND

• Moskowitz CH, Nimer SD, Zelenetz AD, Trippett T, Hedrick EE, Filippa DA, Louie D, Gonzales M, Walits J, Coady-Lyons N, Qin J, Frank R, Bertino JR, Goy A, Noy A, O'Brien JP, Straus D, Portlock CS, Yahalom J. A 2-step comprehensive high-dose chemoradiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model. Blood. 2001 Feb 1;97(3):616-23. doi: 10.1182/blood.v97.3.616.

  PMID: 11157476 BACKGROUND

• Josting A, Engert A, Diehl V, Canellos GP. Prognostic factors and treatment outcome in patients with primary progressive and relapsed Hodgkin's disease. Ann Oncol. 2002;13 Suppl 1:112-6. doi: 10.1093/annonc/13.s1.112. No abstract available.

  PMID: 12078891 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Hodgkin Disease

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Dr. Kevin C. Conlon
• Organization: National Cancer Institute

gconlonkc@mail.nih.gov

240-858-3570

Study Officials

• Kevin C Conlon, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 5, 2011
• First Posted: November 9, 2011
• Study Start: October 11, 2011
• Primary Completion: November 16, 2014
• Study Completion: October 22, 2020
• Last Updated: October 6, 2021
• Results First Posted: May 25, 2017

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)