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Lymphoma, B-CellPhase 1NCT00271050

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

A Phase 1 study testing external beam radiotherapy plus 90-Y ibritumomab tiuxetan in people with Lymphoma, B-Cell, run by The Cleveland Clinic at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma, B-Cell
What is being tested?
external beam radiotherapy plus 90-Y ibritumomab tiuxetan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteUnited States
Study dates
Dec 2005to Jun 2010
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 23Show fewer
  • 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
  • Expected survival greater than or equal to 3 months
  • Prestudy performance status of 0, 1, or 2 according to WHO
  • Absolute neutrophil count ([segmented neutrophils + bands] x total WBC) > 1500/mm3 within two weeks prior to first dose of external beam radiation and also documented again two weeks prior to 90Y-ibritumomab tiuxetan treatment
  • Platelet counts greater than or equal to 100,000 within two weeks prior to first dose of external beam radiation and also documented again two weeks prior to 90Y-ibritumomab tiuxetan treatment
  • Bone marrow involvement by NHL less than 26% within six weeks of treatment with 90Y-ibritumomab tiuxetan
  • Cellularity of bone marrow > 15% within 6 weeks of study
  • Female patients who are not pregnant or lactating
  • Men and women of reproductive potential who are following accepted birth control methods (as determined by the treating physician, abstinence is an acceptable method)

Who cannot join

  • 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
Show all 13Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Cleveland Clinic

    Cleveland, Ohio, 44195

Other trials in United States

About this study

Official title: The Role of Conformal External Beam Radiotherapy in the Management of Patients With Bulky Disease Undergoing Y90-Ibritumomab Tiuxetan (Zevalin) Radio-immunotherapy for Indolent B-cell Non-Hodgkin's Lymphoma

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).

Read the detailed description

Non-Hodgkin's lymphomas (NHL) are a heterogeneous group of lymphoid malignancies that represent the 6th leading cause of cancer death and the 2nd fastest growing cancer in the United States. NHLs can be divided into two prognostic groups: aggressive and indolent lymphomas. Aggressive NHLs grow rapidly and present as disseminated disease in 70% of cases, yet can be cured in a significant number of patients with intensive combination chemotherapy regimens. Indolent (low-grade) NHLs are slow growing malignancies with long natural histories that are incurable when disseminated. Early stage low-grade NHL (stage I and II) has the potential for cure with radiotherapy, but only 10-20% of patients with low-grade NHL present with early stage disease. The vast majority of patients with low-grade NHL present with advanced disseminated disease. While indolent B-cell NHLs have initial sensitivity to chemotherapy and radiotherapy, they frequently relapse and become increasingly resistant to therapy with each successive relapse, eventually transforming to aggressive lymphomas in most patients. Fifty percent of patients presenting with advanced indolent NHL die within 5 years of their first relapse. Only modest improvement has been made in the last 25 years in increasing the survival of patients with indolent NHL with current median survival of 7-10 years.

Recent advances in the field of immunotherapy have proved to benefit patients with relapsed or refractory B-cell NHL. In 1997, rituximab became the first FDA-approved monoclonal antibody (mAb) for the treatment of cancer. Rituximab, a chimeric IgG1 kappa monoclonal antibody, specifically recognizes and binds to the CD20 antigen found on the cell surface of most normal B-cells and malignant B-cell lymphomas. Rituximab binds human complement and lyses B-cell lines through complement dependent cytotoxicity and antibody dependent cellular toxicity. A multi-center Phase II trial of 166 patients with relapsed indolent B-cell lymphoma treated with rituximab found an overall response in 50% of patients with 6% having a complete response and 44% having a partial response. Time to progression was a median of 13 months in patients who responded.

The introduction of radioimmunotherapy (RIT) has exploited the tumor cell targeting ability of mAbs to deliver doses of radiation to the tumor and limited surrounding tissue. This is especially useful in the treatment of NHL because lymphomas are highly sensitive to radiotherapy. 90Yttrium-ibritumomab tiuxetan (Zevalin) is a unique compound composed of the murine IgG1 anti-CD20 antibody ibritumomab, the linker chelator tiuxetan, and the radioisotope 90Y chelated via the linker. 90Y-ibritumomab tiuxetan can be described as providing a double hit therapeutic approach by having the CD20+ antibody properties of rituximab combined with radiation therapy.

90Yttrium-ibritumomab tiuxetan appears to be effective in the treatment of patients refractory to treatment with rituximab, but response rates decrease with increasing tumor size. 90Y-ibritumomab tiuxetan was approved by the FDA in 2002 for the treatment of patients with relapsed or refractory low-grade, follicular, or CD20+ transformed B-cell non-Hodgkin's lymphoma (NHL), and rituximab-refractory follicular NHL.

A preliminary survey of 20 patients treated with 90Y-ibritumomab tiuxetan at the Cleveland Clinic Foundation from 1998-2003 detailed patterns of NHL recurrence after treatment. The results of this survey were presented in part by Dr. Macklis at the 2004 annual meeting of the American Society of Therapeutic Radiation Oncology (ASTRO) in Atlanta and recently accepted for publication in the International Journal of Radiation Oncology, Biology, Physics. Based on preliminary data, a hypothesis can be made that some likely sites of disease recurrence/progression after RIT can be predicted by the volume of disease at a specific site prior to RIT. In short, pre-RIT bulky sites of disease are the most likely locations of disease recurrence after RIT followed by gross, but non-bulky, pre-RIT sites followed by entirely new sites. Based on this hypothesis, it might be beneficial to pre-treat bulky sites of NHL with external beam radiotherapy prior to RIT in order to promote a more durable response. Doses of external beam radiation required to consolidate these bulky disease sites are unclear.

In this study, we plan to utilize a dose of EBRT of 2,400cGy to bulky sites of disease followed by RIT. Though the combined effects of 2,400cGy of EBRT and RIT are likely to be well tolerated, such a combination has not been sufficiently studied. Therefore, the primary goal of this study is to determine if the combination of EBRT and RIT has an acceptable toxicity profile with regard to long-term myelosuppression and other non-hematological toxicities.

Being tested
external beam radiotherapy plus 90-Y ibritumomab tiuxetan
Keywords
non-Hodgkin's lymphoma, external beam radiotherapy (EBRT), radio-immunotherapy (RIT), Zevalin
Medical subject headings
Lymphoma, B-Cell, Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • external beam radiotherapy plus 90-Y ibritumomab tiuxetanOther

    Also called Zevalin

    combination of EBRT followed by radioimmunotherapeutic 90-Y ibritumomab tiuxetan

Study groups in NCT00271050
Study groupRoleWhat they receive
1ExperimentalNot described
Receives: Other: external beam radiotherapy plus 90-Y ibritumomab tiuxetan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. PET and CT (w/oral and IV contrast)

    Measured: 90 days after treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Dec 2005 (estimated)
  2. Study startDec 2005
  3. Primary completionDec 2007
  4. Study completionJun 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00271050
Sponsor's protocol ID
IRB 7883
Other IDs
CCF IRB 7883, Case 1405
Status last verified
Dec 2010
First submitted
28 Dec 2005
Last updated
21 Dec 2010
Results posted
No

Publications

  • 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.

    PubMed 12728402
  • 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.

    PubMed 12177115
  • 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.

    PubMed 14596518
  • 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.

    PubMed 12955576
  • Seymour JF. New treatment approaches to indolent non-Hodgkin's lymphoma. Semin Oncol. 2004 Feb;31(1 Suppl 2):27-32.

    PubMed 15042532
  • 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.

    PubMed 14710396
  • 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.

    PubMed 9704735
  • 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.

    PubMed 12393555
  • 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.

    PubMed 10577851
  • 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.

    PubMed 12011122
  • 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

  • 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.

    PubMed 12692689
  • 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.

    PubMed 12837154
  • 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.

    PubMed 11083548
  • 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.

    PubMed 2045935

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing external beam radiotherapy plus 90-Y ibritumomab tiuxetan in people with Lymphoma, B-Cell, run by The Cleveland Clinic at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Dec 2010. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PET and CT (w/oral and IV contrast) (time frame: 90 days after treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00271050, which also lists 30 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2010.

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