LymphomaPhase 2NCT00058422
Rituximab and Combination Chemotherapy Combined With Yttrium Y 90 Ibritumomab Tiuxetan in Treating Older Patients With Previously Untreated B-Cell Lymphoma
A Phase 2 study testing darbepoetin alfa, filgrastim and rituximab in people with Lymphoma, run by Memorial Sloan Kettering Cancer Center at 2 sites in United States.
Trial summary
RATIONALE: Monoclonal antibodies such as rituximab and yttrium Y 90 ibritumomab tiuxetan can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells. Read more about this study
- Who is it for?
- Ages 60 to 120 years
- Conditions the study is for
- Lymphoma
- What is being tested?
- darbepoetin alfa, filgrastim and rituximab
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 2 sitesUnited States
- Study dates
- 10 Feb 2003to 14 Nov 2019
- 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 60 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed diffuse large B-cell lymphoma, including any of the following subtypes:
- Centroblastic
- Immunoblastic
- T-cell/histiocyte-rich
- Lymphomatoid granulomatosis type
- Anaplastic large B-cell
- Plasmablastic
- Mediastinal
- Intravascular large B-cell lymphoma
- Previously untreated
- High-intermediate or high-risk disease, defined by an age-adjusted international prognostic index score of 2 or 3 (with 1 point each assigned for a ECOG greater than 1/Karnofsky less than 80%, lactate dehydrogenase greater than normal, and stage III or IV)
- Lymphomas with discordant histology and a diffuse large B-cell component are eligible
- Must have an initial diagnostic specimen that is CD20+
- At least Ann Arbor stage II disease
- No confinement of disease to an involved-field radiotherapy port (stage I or limited stage II disease)
- Bidimensionally measurable disease with at least 1 lymph node at least 2.0 cm by 2.0 cm by physical examination, CT scan, or positron-emission tomography
- Bone marrow cellularity greater than 15%
- No known brain or leptomeningeal metastases
- No primary effusion lymphomas
PATIENT CHARACTERISTICS:
Age
- 60 and over* NOTE: *Patients 60 to 65 years of age must be deemed ineligible for autologous stem cell transplantation
Performance status
- Karnofsky 50-100%
Life expectancy
- Not specified
Hematopoietic
- Not specified
Hepatic
- Bilirubin no greater than 2.0 mg/dL (except for Gilbert's disease)
Renal
- Creatinine no greater than 1.5 mg/dL* OR
- Creatinine clearance greater than 50 mL/min* NOTE: *Patients not meeting either criterion but who have renal insufficiency directly related to lymphomatous involvement of the kidneys or renal collecting system are allowed
Cardiovascular
- Cardiac ejection fraction at least 50% by echocardiogram
- No acute myocardial infarction within the past 3 months
- No uncontrolled hypertension
- No New York Heart Association class III or IV congestive heart failure
- No unstable angina pectoris
Other
- Not pregnant or nursing
- Fertile patients must use effective contraception
- HIV negative
- B12 and folate greater than the lower limit of normal
- Transferrin saturation at least 15%
- Ferritin greater than 10 µg/L
- At least 6 weeks since prior RBC donation
- No active seizure disorder
- Prior seizure disorder allowed if free of antiseizure medication and evidence of seizure activity for the past 5 years
- No concurrent uncontrolled medical problems that would preclude administration of chemotherapy or radioimmunotherapy
- No other concurrent malignancy treated with chemotherapy or radiotherapy except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
PRIOR CONCURRENT THERAPY:
Biologic therapy
- At least 4 weeks since prior RBC transfusion
- No prior biologic therapy
- No other concurrent biologic therapy
Chemotherapy
- No prior chemotherapy (one course of R-CHOP allowed)
- No other concurrent standard or investigational chemotherapy
Endocrine therapy
- No more than 7 consecutive days of prior steroids (premedication allowed for prior intravenous contrast allergy)
- No other concurrent corticosteroids
Radiotherapy
- No prior radiotherapy
Surgery
- Not specified
Trial locations and contacts
2 sites in 1 country.
United States2 sites
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, 77030-4009
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: A Phase II Study of R-CHOP and Ibritumomab Tiuxetan (Zevalin) for Elderly Patients With Previously Untreated Diffuse Large B-Cell Lymphoma
RATIONALE: Monoclonal antibodies such as rituximab and yttrium Y 90 ibritumomab tiuxetan can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining rituximab and combination chemotherapy with yttrium Y 90 ibritumomab tiuxetan may kill more cancer cells.
PURPOSE: Phase II trial to study the effectiveness of combining rituximab and combination chemotherapy with yttrium Y 90 ibritumomab tiuxetan in treating older patients who have B-cell lymphoma that has not been previously treated.
Read the detailed description
OBJECTIVES:
- Determine the progression-free and overall survival of patients age 60 and over with previously untreated diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) combined with yttrium Y 90 ibritumomab tiuxetan.
- Determine the incidence of adverse experiences, hematologic toxicity (WBC, hemoglobin, and platelet nadirs; and transfusion requirements), cardiac toxicity (incidence of left ventricular dysfunction and cardiomyopathy by echocardiography), and the development of human antimouse antibody/human anti-chimeric antibody in patients treated with this regimen.
- Determine the predictive value of detecting minimal residual disease by molecular techniques for future relapse/recurrence in patients treated with this regimen.
- Determine the response rate of patients treated with this regimen.
- Determine the red blood cell transfusion requirements, change in hemoglobin from baseline, and incidence of anemia with prophylactic darbepoetin alfa support in patients treated with this regimen.
- Determine the conversion rate to complete remission in patients treated with ibritumomab tiuxetan who achieve a partial remission post-R-CHOP.
- Determine the effect of darbepoetin alfa on the quality of life of these patients.
OUTLINE: This is an open-label, nonrandomized study.
- Chemotherapy: Patients receive rituximab IV over 2-5 hours, cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1; oral prednisone on days 1-5 or 2-6; and filgrastim (G-CSF) subcutaneously (SC) on days 7-15. Patients also receive darbepoetin alfa SC on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
- Radioimmunotherapy: Patients receive rituximab IV over 3-5 hours and indium In 111 ibritumomab tiuxetan (IDEC-In2B8) IV over 10 minutes on day 0.
Patients undergo gamma camera imaging at 2-24 hours and 48-72 hours after the injection of IDEC-In2B8 to observe the flow of ibritumomab tiuxetan. If the flow is deemed safe, then patients receive yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 7.
Quality of life is assessed at baseline, before course 5 of chemotherapy, before radioimmunotherapy, and at 3 months.
Patients are followed every 3 months for 1 year and then every 6 months for 4 years.
PROJECTED ACCRUAL: A total of 65 patients will be accrued for this study.
- Conditions
- Lymphoma
- Being tested
- darbepoetin alfa, filgrastim, rituximab, cyclophosphamide, doxorubicin hydrochloride
- Keywords
- noncontiguous stage II adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma
- Medical subject headings
- Lymphoma, Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
darbepoetin alfaBiological
filgrastimBiological
rituximabBiological
cyclophosphamideDrug
prednisoneDrug
indium In 111 ibritumomab tiuxetanRadiation
yttrium Y 90 ibritumomab tiuxetanRadiation
| Study group | Role | What they receive |
|---|---|---|
| R-CHOP and Ibritumomab Tiuxetan (Zevalin) | Experimental | Chemotherapy: Patients receive rituximab IV over 2-5 hours, cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1; oral prednisone on days 1-5 or 2-6; and filgrastim (G-CSF) subcutaneously (SC) on days 7-15. Patients also receive darbepoetin alfa SC on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Radioimmunotherapy: Patients receive rituximab IV over 3-5 hours and indium In 111 ibritumomab tiuxetan (IDEC-In2B8) IV over 10 minutes on day 0.
Patients undergo gamma camera imaging at 2-24 hours and 48-72 hours after the injection of IDEC-In2B8 to observe the flow of ibritumomab tiuxetan. If the flow is deemed safe, then patients receive yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 7. Quality of life is assessed at baseline, before course 5 of chemotherapy, before radioimmunotherapy, and at 3 months. Patients are followed every 3 months for 1 year and then every 6 months for 4 years. Receives: Biological: darbepoetin alfa; Biological: filgrastim; Biological: rituximab; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: prednisone; Drug: vincristine sulfate; Radiation: indium In 111 ibritumomab tiuxetan; Radiation: yttrium Y 90 ibritumomab tiuxetan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Measured: 2 years
Progression-free Survival
Measured: 2 years
Event-free Survival
Measured: 2 years
Incidence of Adverse Experiences
Determine the incidence of adverse experiences, hematologic toxicity (WBC, hemoglobin, and platelet nadirs; and transfusion requirements), cardiac toxicity (incidence of left ventricular dysfunction and cardiomyopathy by echocardiography), and the development of human antimouse antibody/human anti-chimeric antibody in patients treated with this regimen.
Measured: 2 years
Secondary outcomes (1)
Conversion Rate to Complete Remission
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2003 (estimated)
- Study start10 Feb 2003
- Primary completion14 Nov 2019
- Study completion14 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Paul A. Hamlin, MD, Study chair, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00058422
- Sponsor's protocol ID
- 02-090
- Other IDs
- MSKCC-02090
- Status last verified
- Oct 2020
- First submitted
- 7 Apr 2003
- Last updated
- 12 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of R-CHOP and Ibritumomab Tiuxetan (Zevalin) for Elderly Patients With Previously Untreated Diffuse Large B-Cell Lymphoma
- ClinicalTrials.gov ID
- NCT00058422
- Acronym / sponsor ID
- 02-090
- Conditions
- Lymphoma
- Keywords
- noncontiguous stage II adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 10 Feb 2003 (actual)
- Primary completion
- 14 Nov 2019 (actual)
- Study completion
- 14 Nov 2019 (actual)
- First posted
- 9 Apr 2003 (estimated)
- Results
- Posted 12 Nov 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Monoclonal antibodies such as rituximab and yttrium Y 90 ibritumomab tiuxetan can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining rituximab and combination chemotherapy with yttrium Y 90 ibritumomab tiuxetan may kill more cancer cells.
PURPOSE: Phase II trial to study the effectiveness of combining rituximab and combination chemotherapy with yttrium Y 90 ibritumomab tiuxetan in treating older patients who have B-cell lymphoma that has not been previously treated.
Detailed description
OBJECTIVES:
- Determine the progression-free and overall survival of patients age 60 and over with previously untreated diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) combined with yttrium Y 90 ibritumomab tiuxetan.
- Determine the incidence of adverse experiences, hematologic toxicity (WBC, hemoglobin, and platelet nadirs; and transfusion requirements), cardiac toxicity (incidence of left ventricular dysfunction and cardiomyopathy by echocardiography), and the development of human antimouse antibody/human anti-chimeric antibody in patients treated with this regimen.
- Determine the predictive value of detecting minimal residual disease by molecular techniques for future relapse/recurrence in patients treated with this regimen.
- Determine the response rate of patients treated with this regimen.
- Determine the red blood cell transfusion requirements, change in hemoglobin from baseline, and incidence of anemia with prophylactic darbepoetin alfa support in patients treated with this regimen.
- Determine the conversion rate to complete remission in patients treated with ibritumomab tiuxetan who achieve a partial remission post-R-CHOP.
- Determine the effect of darbepoetin alfa on the quality of life of these patients.
OUTLINE: This is an open-label, nonrandomized study.
- Chemotherapy: Patients receive rituximab IV over 2-5 hours, cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1; oral prednisone on days 1-5 or 2-6; and filgrastim (G-CSF) subcutaneously (SC) on days 7-15. Patients also receive darbepoetin alfa SC on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
- Radioimmunotherapy: Patients receive rituximab IV over 3-5 hours and indium In 111 ibritumomab tiuxetan (IDEC-In2B8) IV over 10 minutes on day 0.
Patients undergo gamma camera imaging at 2-24 hours and 48-72 hours after the injection of IDEC-In2B8 to observe the flow of ibritumomab tiuxetan. If the flow is deemed safe, then patients receive yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 7.
Quality of life is assessed at baseline, before course 5 of chemotherapy, before radioimmunotherapy, and at 3 months.
Patients are followed every 3 months for 1 year and then every 6 months for 4 years.
PROJECTED ACCRUAL: A total of 65 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| R-CHOP and Ibritumomab Tiuxetan (Zevalin) | Experimental | Biological: darbepoetin alfa, Biological: filgrastim, Biological: rituximab, Drug: cyclophosphamide, Drug: doxorubicin hydrochloride, Drug: prednisone, Drug: vincristine sulfate, Radiation: indium In 111 ibritumomab tiuxetan, Radiation: yttrium Y 90 ibritumomab tiuxetanChemotherapy: Patients receive rituximab IV over 2-5 hours, cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1; oral prednisone on days 1-5 or 2-6; and filgrastim (G-CSF) subcutaneously (SC) on days 7-15. Patients also receive darbepoetin alfa SC on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Radioimmunotherapy: Patients receive rituximab IV over 3-5 hours and indium In 111 ibritumomab tiuxetan (IDEC-In2B8) IV over 10 minutes on day 0. Patients undergo gamma camera imaging at 2-24 hours and 48-72 hours after the injection of IDEC-In2B8 to observe the flow of ibritumomab tiuxetan. If the flow is deemed safe, then patients receive yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 7. Quality of life is assessed at baseline, before course 5 of chemotherapy, before radioimmunotherapy, and at 3 months. Patients are followed every 3 months for 1 year and then every 6 months for 4 years. |
Who may qualify
- Ages
- 60 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| darbepoetin alfa | Biological | R-CHOP and Ibritumomab Tiuxetan (Zevalin) |
| filgrastim | Biological | R-CHOP and Ibritumomab Tiuxetan (Zevalin) |
| rituximab | Biological | R-CHOP and Ibritumomab Tiuxetan (Zevalin) |
| cyclophosphamide | Drug | R-CHOP and Ibritumomab Tiuxetan (Zevalin) |
| doxorubicin hydrochloride | Drug | R-CHOP and Ibritumomab Tiuxetan (Zevalin) |
| prednisone | Drug | R-CHOP and Ibritumomab Tiuxetan (Zevalin) |
| vincristine sulfate | Drug | R-CHOP and Ibritumomab Tiuxetan (Zevalin) |
| indium In 111 ibritumomab tiuxetan | Radiation | R-CHOP and Ibritumomab Tiuxetan (Zevalin) |
| yttrium Y 90 ibritumomab tiuxetan | Radiation | R-CHOP and Ibritumomab Tiuxetan (Zevalin) |
Primary outcome
Overall Survival
Time frame: 2 years
Progression-free Survival
Time frame: 2 years
Event-free Survival
Time frame: 2 years
Incidence of Adverse Experiences
Time frame: 2 years
Determine the incidence of adverse experiences, hematologic toxicity (WBC, hemoglobin, and platelet nadirs; and transfusion requirements), cardiac toxicity (incidence of left ventricular dysfunction and cardiomyopathy by echocardiography), and the development of human antimouse antibody/human anti-chimeric antibody in patients treated with this regimen.
1 secondary outcome
Conversion Rate to Complete Remission
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul A. Hamlin, MD study chair
Memorial Sloan Kettering Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing darbepoetin alfa, filgrastim and rituximab in people with Lymphoma, run by Memorial Sloan Kettering Cancer Center at 2 sites 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?
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 12 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 12 Nov 2020). 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?
Overall Survival (time frame: 2 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Nov 2020.