External Beam Radiotherapy and Zevalin for Management of Indolent B-Cell Non-Hodgkin's Lymphoma

NCT00271050 | Completed Phase 1

• 3 other identifiers: IRB 7883CCF IRB 7883Case 1405
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the research study is to learn whether external beam radiation can be used as a safe and effective treatment for patients with bulky (≥ 5cm) sites of non-Hodgkin's lymphoma prior to treatment with 90Y-ibritumomab tiuxetan (Zevalin).

Conditions

Lymphoma, B-Cell

Keywords

non-Hodgkin's lymphoma; external beam radiotherapy (EBRT); radio-immunotherapy (RIT); Zevalin

Outcome Measures

Primary Outcomes (1)

• PET and CT (w/oral and IV contrast)

  90 days after treatment

Study Arms (1)

1

EXPERIMENTAL

Other: external beam radiotherapy plus 90-Y ibritumomab tiuxetan

Interventions

external beam radiotherapy plus 90-Y ibritumomab tiuxetan OTHER

combination of EBRT followed by radioimmunotherapeutic 90-Y ibritumomab tiuxetan

Also known as: Zevalin

1

Eligibility Criteria

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

You may qualify if:

• B-cell non-Hodgkin's lymphoma of one of the following types as defined by the WHO classification:
• Small lymphocytic lymphoma/Chronic lymphocytic leukemia
• Nodal marginal zone B-cell lymphoma
• Extranodal marginal zone B-cell lymphoma
• Splenic marginal zone lymphoma
• Lymphoplasmacytic lymphoma
• Follicular lymphoma
• Diffuse large B-cell lymphoma which has transformed from one of the previously listed types of lymphomas
• At least one site of lymphoma greater than or equal to 5 cm in any dimension
• Received at least one prior therapy
• Should show evidence of symptomatology as a result of their disease and/or evidence of progression of their disease.
• Measurable disease using Cheson criteria \[23\] for Non-Hodgkin's Lymphoma: a lymph node that is greater than 1 cm in its longest transverse diameter by CT scan should be considered compatible with involvement by NHL
• No anti-cancer therapy for four weeks (six weeks if rituximab, nitrosourea or Mitomycin C) prior to study initiation, and fully recovered from all toxicities associated with prior surgery, radiation treatments, chemotherapy, or immunotherapy
• An IRB-approved signed informed consent
• Age greater than or equal to 18

You may not qualify if:

• Prior radioimmunotherapy
• Presence of CNS lymphoma
• Absolute lymphocyte count ≥ 5000
• HIV or AIDS-related lymphoma
• Large pleural effusions or ascites
• Total bilirubin \> 2.0 mg/dL
• Serum creatinine \> 2.0 mg/dL
• Patients who, in the opinion of their oncology team, have prior external beam radiation therapy to \> 25% of active skeletal marrow (either involved field or regional)
• Patients who have received G-CSF or GM-CSF therapy within two weeks or pegfilgrastim within 4 weeks prior to treatment
• Serious nonmalignant disease or infection which, in the opinion of the investigator, would compromise other protocol objectives
• Major surgery, other than diagnostic surgery, within four weeks
• Pregnant women or women of child-bearing age who refuse pregnancy tests
• Patients who have had prior myeloablative autologous or allogenic stem cell transplantation

Sponsors & Collaborators

• The Cleveland Clinic: lead

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Related Publications (30)

• Fisher RI. Overview of non-Hodgkin's lymphoma: biology, staging, and treatment. Semin Oncol. 2003 Apr;30(2 Suppl 4):3-9. doi: 10.1053/sonc.2003.23797.

  PMID: 12728402 BACKGROUND

• Dillman RO. Radiolabeled anti-CD20 monoclonal antibodies for the treatment of B-cell lymphoma. J Clin Oncol. 2002 Aug 15;20(16):3545-57. doi: 10.1200/JCO.2002.02.126. No abstract available.

  PMID: 12177115 BACKGROUND

• Gustavsson A, Osterman B, Cavallin-Stahl E. A systematic overview of radiation therapy effects in non-Hodgkin's lymphoma. Acta Oncol. 2003;42(5-6):605-19. doi: 10.1080/02841860310014435.

  PMID: 14596518 BACKGROUND

• Tobinai K. Rituximab and other emerging antibodies as molecular target-based therapy of lymphoma. Int J Clin Oncol. 2003 Aug;8(4):212-23. doi: 10.1007/s10147-003-0295-y.

  PMID: 12955576 BACKGROUND

• Seymour JF. New treatment approaches to indolent non-Hodgkin's lymphoma. Semin Oncol. 2004 Feb;31(1 Suppl 2):27-32.

  PMID: 15042532 BACKGROUND

• Forero A, Lobuglio AF. History of antibody therapy for non-Hodgkin's lymphoma. Semin Oncol. 2003 Dec;30(6 Suppl 17):1-5. doi: 10.1053/j.seminoncol.2003.10.002.

  PMID: 14710396 BACKGROUND

• McLaughlin P, Grillo-Lopez AJ, Link BK, Levy R, Czuczman MS, Williams ME, Heyman MR, Bence-Bruckler I, White CA, Cabanillas F, Jain V, Ho AD, Lister J, Wey K, Shen D, Dallaire BK. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998 Aug;16(8):2825-33. doi: 10.1200/JCO.1998.16.8.2825.

  PMID: 9704735 BACKGROUND

• Cheson BD. Radioimmunotherapy of non-Hodgkin lymphomas. Blood. 2003 Jan 15;101(2):391-8. doi: 10.1182/blood-2002-06-1793. Epub 2002 Sep 19.

  PMID: 12393555 BACKGROUND

• Witzig TE, White CA, Wiseman GA, Gordon LI, Emmanouilides C, Raubitschek A, Janakiraman N, Gutheil J, Schilder RJ, Spies S, Silverman DH, Parker E, Grillo-Lopez AJ. Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20(+) B-cell non-Hodgkin's lymphoma. J Clin Oncol. 1999 Dec;17(12):3793-803. doi: 10.1200/JCO.1999.17.12.3793.

  PMID: 10577851 BACKGROUND

• Witzig TE, Gordon LI, Cabanillas F, Czuczman MS, Emmanouilides C, Joyce R, Pohlman BL, Bartlett NL, Wiseman GA, Padre N, Grillo-Lopez AJ, Multani P, White CA. Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2002 May 15;20(10):2453-63. doi: 10.1200/JCO.2002.11.076.

  PMID: 12011122 BACKGROUND

• Justice TE, Martenson JA, Wiseman GA, Witzig TE. External beam radiation therapy after 90Y-ibritumomab tiuxetan radioimmunotherapy for relapsed or refractory CD20+ non-Hodgkin's lymphoma. Int J Radiat Oncol Biol Phys 2003; 57(Suppl 2):S287-8

  BACKGROUND

• O'Doherty MJ, Hoskin PJ. Positron emission tomography in the management of lymphomas: a summary. Eur J Nucl Med Mol Imaging. 2003 Jun;30 Suppl 1:S128-30. doi: 10.1007/s00259-003-1170-9. Epub 2003 Apr 12. No abstract available.

  PMID: 12692689 BACKGROUND

• Blum RH, Seymour JF, Wirth A, MacManus M, Hicks RJ. Frequent impact of [18F]fluorodeoxyglucose positron emission tomography on the staging and management of patients with indolent non-Hodgkin's lymphoma. Clin Lymphoma. 2003 Jun;4(1):43-9. doi: 10.3816/clm.2003.n.013.

  PMID: 12837154 BACKGROUND

• Kostakoglu L, Goldsmith SJ. Fluorine-18 fluorodeoxyglucose positron emission tomography in the staging and follow-up of lymphoma: is it time to shift gears? Eur J Nucl Med. 2000 Oct;27(10):1564-78. doi: 10.1007/s002590000340.

  PMID: 11083548 BACKGROUND

• Leskinen-Kallio S, Ruotsalainen U, Nagren K, Teras M, Joensuu H. Uptake of carbon-11-methionine and fluorodeoxyglucose in non-Hodgkin's lymphoma: a PET study. J Nucl Med. 1991 Jun;32(6):1211-8.

  PMID: 2045935 BACKGROUND

• Okada J, Yoshikawa K, Imazeki K, Minoshima S, Uno K, Itami J, Kuyama J, Maruno H, Arimizu N. The use of FDG-PET in the detection and management of malignant lymphoma: correlation of uptake with prognosis. J Nucl Med. 1991 Apr;32(4):686-91.

  PMID: 2013808 BACKGROUND

• Newman JS, Francis IR, Kaminski MS, Wahl RL. Imaging of lymphoma with PET with 2-[F-18]-fluoro-2-deoxy-D-glucose: correlation with CT. Radiology. 1994 Jan;190(1):111-6. doi: 10.1148/radiology.190.1.8259386.

  PMID: 8259386 BACKGROUND

• Torizuka T, Zasadny KR, Kison PV, Rommelfanger SG, Kaminski MS, Wahl RL. Metabolic response of non-Hodgkin's lymphoma to 131I-anti-B1 radioimmunotherapy: evaluation with FDG PET. J Nucl Med. 2000 Jun;41(6):999-1005.

  PMID: 10855624 BACKGROUND

• Scheidhauer K, Wolf I, Baumgartl HJ, Von Schilling C, Schmidt B, Reidel G, Peschel C, Schwaiger M. Biodistribution and kinetics of (131)I-labelled anti-CD20 MAB IDEC-C2B8 (rituximab) in relapsed non-Hodgkin's lymphoma. Eur J Nucl Med Mol Imaging. 2002 Oct;29(10):1276-82. doi: 10.1007/s00259-002-0820-7. Epub 2002 Jul 6.

  PMID: 12271407 BACKGROUND

• Hofmann M, Hertenstein B, Boerner AR, Heil G, Peest D, Knoop BO, Geworski L, Otto D, Ganser A, Knapp WH. 18-F-FDG-PET in monitoring therapy response to RIT by 131-I Rituximab (Mabthera) antibody. Annals Onc 2002; 13 (Suppl 2): 96.

  BACKGROUND

• Macklis R, Molina A, Pohlman B, Gordon L, Wang H, Saville MW, Witzig T. Long-term responses in patients with relapsed or refractory follicular lymphoma treated with yttrium 90 ibritumomab tiuxetan (Zevalin). Int J Radiat Oncol Biol Phys 2004; 60 (Suppl 1): S542 (2346).

  BACKGROUND

• Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-Lopez A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999 Apr;17(4):1244. doi: 10.1200/JCO.1999.17.4.1244.

  PMID: 10561185 BACKGROUND

• Gordon LI, Molina A, Witzig T, Emmanouilides C, Raubtischek A, Darif M, Schilder RJ, Wiseman G, White CA. Durable responses after ibritumomab tiuxetan radioimmunotherapy for CD20+ B-cell lymphoma: long-term follow-up of a phase 1/2 study. Blood. 2004 Jun 15;103(12):4429-31. doi: 10.1182/blood-2003-11-3883. Epub 2004 Mar 11.

  PMID: 15016644 BACKGROUND

• Witzig TE, White CA, Gordon LI, Wiseman GA, Emmanouilides C, Murray JL, Lister J, Multani PS. Safety of yttrium-90 ibritumomab tiuxetan radioimmunotherapy for relapsed low-grade, follicular, or transformed non-hodgkin's lymphoma. J Clin Oncol. 2003 Apr 1;21(7):1263-70. doi: 10.1200/JCO.2003.08.043.

  PMID: 12663713 BACKGROUND

• Chen EX, Tannock IF. Risks and benefits of phase 1 clinical trials evaluating new anticancer agents: a case for more innovation. JAMA. 2004 Nov 3;292(17):2150-1. doi: 10.1001/jama.292.17.2150. No abstract available.

  PMID: 15523076 BACKGROUND

• Eisenhauer EA, O'Dwyer PJ, Christian M, Humphrey JS. Phase I clinical trial design in cancer drug development. J Clin Oncol. 2000 Feb;18(3):684-92. doi: 10.1200/JCO.2000.18.3.684.

  PMID: 10653884 BACKGROUND

• Yahalom J, Mauch P. The involved field is back: issues in delineating the radiation field in Hodgkin's disease. Ann Oncol. 2002;13 Suppl 1:79-83. doi: 10.1093/annonc/13.s1.79.

  PMID: 12078908 BACKGROUND

• Josting A, Rudolph C, Mapara M, Glossmann JP, Sieniawski M, Sieber M, Kirchner HH, Dorken B, Hossfeld DK, Kisro J, Metzner B, Berdel WE, Diehl V, Engert A. Cologne high-dose sequential chemotherapy in relapsed and refractory Hodgkin lymphoma: results of a large multicenter study of the German Hodgkin Lymphoma Study Group (GHSG). Ann Oncol. 2005 Jan;16(1):116-23. doi: 10.1093/annonc/mdi003.

  PMID: 15598948 BACKGROUND

• Chen Q, Chai YC, Mazumder S, Jiang C, Macklis RM, Chisolm GM, Almasan A. The late increase in intracellular free radical oxygen species during apoptosis is associated with cytochrome c release, caspase activation, and mitochondrial dysfunction. Cell Death Differ. 2003 Mar;10(3):323-34. doi: 10.1038/sj.cdd.4401148.

  PMID: 12700632 BACKGROUND

• Kaminski MS, Leonard JP, Zelenetz AD, Vose JM. Bexxar therapy (tositumomab and iodine I-131) has high response rates in the treatment of bulky low grade relapsed or refractory non-Hodgkin's lymphoma. 2002 ASCO Annual Meeting. Abstract #17.

  BACKGROUND

MeSH Terms

Conditions

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin

Interventions

ibritumomab tiuxetan

Condition Hierarchy (Ancestors)

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

Study Officials

• Roger Macklis, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 28, 2005
• First Posted: December 29, 2005
• Study Start: December 1, 2005
• Primary Completion: December 1, 2007
• Study Completion: June 1, 2010
• Last Updated: December 21, 2010

Record last verified: 2010-12

Locations

US (1)