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Contiguous Stage II Adult Diffuse Large Cell LymphomaPhase 2NCT00088881

Rituximab, Combination Chemotherapy, and 90-Yttrium Ibritumomab Tiuxetan for Patients With Stage I or II Non-Hodgkin's Lymphoma

A Phase 2 study testing rituximab, prednisone and cyclophosphamide in people with Contiguous Stage II Adult Diffuse Large Cell Lymphoma and Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase II trial is studying how well giving rituximab together with combination chemotherapy and 90-Yttrium ibritumomab tiuxetan works in treating patients with stage I or stage II lymphoma. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
rituximab, prednisone and cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
1 siteUnited States
Study dates
Dec 2004to Mar 2011
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Patients must have histologically confirmed diagnosis of diffuse large cell lymphoma
  • Patients must be stage I or II (Modified Ann Arbor staging)
  • Baseline measurements and evaluations must be obtained within 4 weeks of registration to the study; abnormal PET scans will not constitute evaluable disease unless verified by CT scan or other appropriate imaging; patients must have at least one objective measurable disease parameter (a lesion with at least 1 dimension > 1.5 cm); or if they are stage 1
  • Stage I patients must have at least one of the following risk factors:
  • Age >= 60 years
  • Bulky disease (>= 5 cm in at least one dimension)
Show all 16Show fewer
  • Elevated Lactate Dehydrogenase (LDH) above institutional upper limit of normal
  • Eastern Cooperative Oncology Group (ECOG) performance status = 2
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Absolute neutrophil count >= 1500/mm^3 (includes neutrophils and bands)
  • Platelet count >= 100,000/mm^3
  • Creatinine < 2.0 mg/dl
  • Total bilirubin < 2 mg/dl (may be up to 3.0 mg/dl if due to liver involvement by lymphoma); patients with elevated total bilirubin should have a direct bilirubin checked; if the direct bilirubin is normal there is no need for a dose reduction
  • Patients must have left ventricular ejection fraction (LVEF) of > 45%
  • Patients must be tested for hepatitis B (HBV) surface antigen within 2 weeks of registration
  • NOTE: Patients who test positive will be allowed to participate but must be followed closely for clinical and laboratory signs of active HBV infection and for signs of hepatitis

Who cannot join

  • Prior chemotherapy, radiation therapy, radioimmunotherapy, or immunotherapy; a short course (=< 14 days prior to registration) of corticosteroids is allowed
  • Evidence of other malignancy:
  • Prior chemotherapy or prior radiation therapy for other malignancies
  • Currently receiving hormone therapy or chemotherapy for another malignancy even if the treatment is being provided in the adjuvant treatment setting, i.e. with no evidence of the original other malignancy
  • Adjuvant hormonal therapy must have been discontinued > 3 months before entering this study
  • Patients are eligible if they meet the following conditions: (a) treated carcinoma-in-situ of the cervix; (b) treated squamous cell or basal cell skin cancer; or (c) any other surgically cured malignancy from which the patient has been disease free for at least 3 years
Show all 11Show fewer
  • Pregnant or breast feeding, as there would be radiation exposure to the fetus or child; a negative pregnancy test is required =< 1 week prior to registration for women of childbearing potential (WOCBP). Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception
  • Known central nervous system (CNS) lymphoma, testicular lymphoma, or vitreous lymphoma
  • Known HIV infection. The safety of Zevalin™ in this population has not been tested at this time
  • Serious coexisting medical condition or active infection which would compromise the ability to deliver standard R-CHOP chemotherapy
  • Evidence of myelodysplasia on bone marrow aspiration and biopsy

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Eastern Cooperative Oncology Group

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: A Phase II Trial of R-CHOP Followed by Zevalin Radioimmunotherapy for Patients With Previously Untreated Stages I and II CD20+ Diffuse Large Cell Non-Hodgkin's Lymphoma

This phase II trial is studying how well giving rituximab together with combination chemotherapy and 90-Yttrium ibritumomab tiuxetan works in treating patients with stage I or stage II lymphoma. Drugs used in chemotherapy, such as prednisone, cyclophosphamide, doxorubicin, and vincristine, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab and yttrium 90-Yttrium ibritumomab tiuxetan can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells. Combining a monoclonal antibody with combination chemotherapy and a radiolabeled monoclonal antibody may kill more cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the complete response rate (CR) and functional CR rate in patients with previously untreated stage I (with at least 1 risk factor) or stage II CD20+ diffuse large cell lymphoma who receive therapy with R-CHOP followed by 90-Yttrium -Zevalin™.

SECONDARY OBJECTIVES:

  1. To evaluate the time to treatment failure, duration of response, and overall survival in these patients who receive therapy with R-CHOP followed by 90-Yttrium -Zevalin™.

II. To evaluate the toxicity of this therapy. III. To evaluate the toxicity of adding involved field radiation therapy > 12 weeks after Zevalin™ for patients with CT+/PET+ residual masses.

TERTIARY OBJECTIVES:

  1. To evaluate PET scans pre -and post - R-CHOP/Zevalin™ therapy.

OUTLINE:

R-CHOP (rituximab, prednisone, cyclophosphamide, doxorubicin,vincristine): Patients receive oral prednisone once daily on days 1-5. Patients also receive rituximab IV over several hours followed by cyclophosphamide IV, doxorubicin IV, and vincristine IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) after 2 courses receive 2 additional courses. Patients achieving a partial response, uncertain CR, or stable disease receive 4 additional courses. Patients are evaluated 3 weeks after the last course of therapy. Patients with progressive disease go off study.

Radioimmunotherapy: Beginning no more than 9 weeks after the reevaluation (or 12 weeks after the last dose of R-CHOP), patients receive rituximab IV on day 1 followed by indium In 111 ibritumomab tiuxetan IV over 10 minutes for imaging studies. Patients then receive rituximab IV followed by yttrium 90-Yttrium ibritumomab tiuxetan IV over 10 minutes on day 8.

Radiotherapy: Patients with residual disease by CT scan or positron emission tomography (PET) scan after 12 weeks after radioimmunotherapy undergo conventional involved-field radiotherapy.

Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually for 5 years.

Medical subject headings
Lymphoma, B-Cell, Marginal Zone, Lymphoma, Large B-Cell, Diffuse, Waldenstrom Macroglobulinemia

What participants receive

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

  • rituximabBiological

    Also called IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8

    Given IV

  • prednisoneDrug

    Also called DeCortin, Deltra

    Given orally

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given IV

  • doxorubicinDrug

    Also called ADM, ADR, Adria, Adriamycin PFS

    Given IV

  • vincristineDrug

    Also called leurocristine sulfate, VCR, Vincasar PFS

    Given IV

  • indium In 111 ibritumomab tiuxetanRadiation

    Also called IDEC-In2B8

    Given IV

  • radiation therapyRadiation

    Also called irradiation, radiotherapy, therapy, radiation

    Undergo radiotherapy

  • positron emission tomographyProcedure or surgery

    Also called FDG-PET, PET, PET scan, tomography, emission computed

    Undergo PET scans

Study groups in NCT00088881
Study groupRoleWhat they receive
TreatmentExperimentalR-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone): Patients receive R-CHOP every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response after 2 courses receive 2 additional courses. Patients achieving a partial response, uncertain CR, or stable disease receive 4 additional courses. Patients with progressive disease go off study. Zevalin™Radioimmunotherapy: Beginning no more than 9 weeks after the last course of R-CHOP, patients receive rituximab IV on day 1 followed by indium In 111 ibritumomab tiuxetan IV over 10 minutes for imaging studies. Patients then receive rituximab IV followed by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 8. Radiation therapy: Patients with residual disease by CT scan or positron emission tomography (PET) scan after 12 weeks after radioimmunotherapy undergo conventional involved-field radiotherapy.
Receives: Biological: rituximab; Drug: prednisone; Drug: cyclophosphamide; Drug: doxorubicin; Drug: vincristine; Radiation: indium In 111 ibritumomab tiuxetan; Radiation: radiation therapy; Procedure: positron emission tomography

What is being measured

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

  1. Complete Response (CR) +Complete Response/Uncertain (CRu) in Patients Treated With R-CHOP Followed by 90-Yttrium -Zevalin™.

    Response was assessed based upon the criteria from the International Workshop to Standardize Criteria for Non-Hodgkin's Lymphoma (Cheson, 1999). CR is defined as complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease related B-symptoms if present prior to therapy, as well as normalization (normal limits of institutional labs) of those biochemical abnormalities (e.g., LDH) definitely attributed to NHL. CRu is defined as meeting the criteria of CR except one or more of the followings: A residual dominant node (or extra-nodal mass) that is currently > 1.5 cm in greatest diameter that has decreased by > 75% from baseline in the product of its diameters. Individual dominant nodes (or extra-nodal masses) that were previously confluent must have decreased by > 75% in SPD compared with the size of the original mass. Indeterminate bone marrow (increased number or size of aggregates without cytologic or architectural atypia).

    Measured: Assessed after 2 cycles of R-CHOP, after completion of R-CHOP, and at Week 12 After 90-Yttrium Zevalin

  2. Functional CR in Patients Treated With R-CHOP Followed by 90-Yttrium -Zevalin™.

    Patients will be considered a functional CR if they meet the criteria for a CR, or if they meet the criteria for a CRu or partial response (PR) by CT and are PET negative. Please see primary outcome #1 for the definition of CR and CRu. PR is defined as: A decrease of >50% in the SPD (sum of products of the diameters) of the six largest (or less) dominant nodes or extra-nodal masses. No increase in the size of the liver or the spleen. No unequivocal progression in any non-measurable or non-dominant site. Splenic and hepatic nodules must regress by >50% in SPD (sum of the products of the diameters). Bone marrow assessment is not relevant for determination of a PR because it is assessable and not measurable disease. No new sites of disease.

    Measured: Assessed after 2 cycles of R-CHOP, after completion of R-CHOP, and at Week 12 After 90-Yttrium Zevalin

Secondary outcomes (2)

  1. 3-year Time to Treatment Failure (TTF) Rate

    Time to treatment failure (TTF) is defined as the time from step 1 registration to disease progression or death. TTF is censored at last documented progression free for cases without progression. The 3-year TTF rate is defined as the probability of patients remaining free from treatment failure at 3 years.

    Measured: Assessed every 3 months for one year; every 4 months for the second year; then every 6 months for 3 years; then annually to 10 years from patient entry.

  2. 3-year Overall Survival (OS) Rate

    Overall survival (OS) is defined as the time from step 1 registration to death of any cause. OS is censored at the date last known alive for cases that are alive. The 3-year OS rate is defined as the probability of patients remaining alive at 3 years.

    Measured: Assessed every 3 months for 2 years, then every 6 months for 3 years; then annually to 10 years from patient entry.

Timeline

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

  1. First posted5 Aug 2004 (estimated)
  2. Study startDec 2004
  3. Primary completionMar 2011
  4. Study completionMar 2011

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
62 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00088881
Sponsor's protocol ID
NCI-2012-02957
Other IDs
E3402, U10CA021115
Status last verified
Apr 2017
First submitted
4 Aug 2004
Last updated
25 May 2017
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing rituximab, prednisone and cyclophosphamide in people with Contiguous Stage II Adult Diffuse Large Cell Lymphoma and Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, run by National Cancer Institute (NCI) 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 16 inclusion and 11 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: stopped early, as of the sponsor's last update on 25 May 2017. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Feb 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Complete Response (CR) +Complete Response/Uncertain (CRu) in Patients Treated With R-CHOP Followed by 90-Yttrium -Zevalin™. (time frame: Assessed after 2 cycles of R-CHOP, after completion of R-CHOP, and at Week 12 After 90-Yttrium Zevalin). The study lists 2 primary outcomes in all. 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 NCT00088881.

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 25 May 2017.

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