LymphomaPhase 2FRAIL-06NCT00911183
Diffuse Large B Cell Non-Hodgkin's Lymphoma in the Vulnerable/Frail Elderly. A Multicentric Randomized Phase II Trial
A Phase 2 study testing filgrastim, pegfilgrastim and rituximab in people with Lymphoma, run by Institut Bergonié at 1 site in France.
Trial summary
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Read more about this study
- Who is it for?
- Ages 70 to 120 years
- Conditions the study is for
- Lymphoma
- What is being tested?
- filgrastim, pegfilgrastim and rituximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- 1 siteFrance
- Study dates
- 2 Dec 2008to 1 Jan 2015
- 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 70 to 120 years
- All sexes
- No healthy volunteers
- Older adult
DISEASE CHARACTERISTICS:
- Diagnosis of diffuse large B-cell non-Hodgkin lymphoma
- Stage II, III, or IV disease (according to the WHO classification), including all morphological and clinical variants
- No Burkitt-like lymphoma (presence of small cells in the bone marrow biopsy allowed)
- CD20+ disease
- Has ≥ 1 measurable target lesion ≥ 1.1 cm (according to the International Workshop Criteria)
- Poor physiological status, as defined by ≥ 1 of the following criteria:
- WHO performance status 3
- Clinical evaluation and measurement of LVEF that would preclude doxorubicin administration (i.e., LVEF < 50%)
- Creatinine clearance < 50 mL/min
- Serum bilirubin > 30 μmol/L
- Severe comorbidity that would preclude the use of CHOP chemotherapy
- Ineligible for standard R-CHOP therapy
- No cerebral or meningeal involvement
PATIENT CHARACTERISTICS:
- WHO performance status 0-3
- ANC > 750/mm^3
- Platelet count > 50,000/mm^3
- LVEF > 35%
- Able to receive either R-COP or R-COPY therapy
- No congestive heart failure, serious arrhythmia, or myocardial infarction within the past 6 months
- No other malignancy within the past 5 years except for adequately treated basal cell carcinoma of the skin or curatively treated carcinoma in situ of the cervix
- No active infection
- No active viral hepatitis B or C by serology
- No known HIV positivity
- No hypersensitivity to rituximab, any of its excipients, or to murine proteins
- No documented history of allergy to eggs or egg products
- No psychological, familial, sociological, or geographical condition that would preclude compliance with study treatment or follow-up schedule
PRIOR CONCURRENT THERAPY:
- No prior therapy for this cancer
- No prior anthracycline administration with a cumulative dose > 240 mg/m² of doxorubicin hydrochloride or > 400 mg/m² of epirubicin hydrochloride
- More than 30 days since prior participation in another clinical trial involving investigational drugs
- No other concurrent antineoplastic agents
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Diffuse Large B Cell Non-Hodgkin's Lymphoma in the Vulnerable/Frail Elderly. A Multicentric Randomized Phase II Trial With Emphasis on Geriatric Assessment and Quality of Life
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, prednisone, and liposome-encapsulated doxorubicin citrate, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It is not yet known whether rituximab and combination chemotherapy are more effective when given together with or without liposome-encapsulated doxorubicin citrate in treating older patients with diffuse large B-cell non-Hodgkin lymphoma.
PURPOSE: This randomized phase II trial is studying the side effects of giving rituximab together with cyclophosphamide, vincristine sulfate, and prednisone with or without liposome-encapsulated doxorubicin citrate and to see how well it works in treating older patients with stage II, stage III, or stage IV diffuse large B-cell non-Hodgkin lymphoma.
Read the detailed description
OBJECTIVES:
Primary
- To assess the therapeutic efficacy of rituximab, cyclophosphamide, vincristine sulfate, and prednisone with vs without liposome-encapsulated doxorubicin citrate, in terms of complete remission rate at 6 months, in vulnerable or frail elderly patients with stage II, III, or IV diffuse large B-cell non-Hodgkin lymphoma.
- To assess the safety of these regimens in these patients.
Secondary
- To evaluate the progression-free survival, event-free survival, and overall survival rates at 6 and 24 months in patients treated with these regimens.
- To evaluate the overall response rate at 6 and 24 months in patients treated with these regimens.
- To evaluate the duration of complete remission in patients treated with these regimens.
- To evaluate the acute side effects (according to the International CTC scale) of these regimens in these patients.
- To evaluate the geriatric condition and quality of life of patients treated with these regimens.
OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.
- Arm I (R-COP regimen): Patients receive rituximab IV, cyclophosphamide IV, and vincristine sulfate IV on day 1. Patients also receive oral prednisone on days 1-5 and filgrastim subcutaneously (SC) on days 8-14 or pegfilgrastim SC on day 2. Treatment repeats every 21 days for at least 3 courses.
- Arm II (R-COPY regimen): Patients receive rituximab, cyclophosphamide, vincristine sulfate, prednisone, and filgrastim or pegfilgrastim as in arm I. Patients also receive liposome-encapsulated doxorubicin citrate IV on day 1. Treatment repeats every 21 days for at least 3 courses.
After 3 courses of R-COP or R-COPY, patients undergo evaluation. Patients with disease progression or a response of < 25% are removed from the study. Patients with a response of ≥ 25% receive 3 more courses of R-COP or R-COPY, followed by rituximab IV alone on day 1 of courses 7 and 8 in the absence of disease progression or unacceptable toxicity.
After the completion of chemotherapy, some patients may undergo radiotherapy.
Patients complete quality of life and geriatric assessment questionnaires at baseline and periodically during study treatment.
After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 2 years.
- Conditions
- Lymphoma
- Being tested
- filgrastim, pegfilgrastim, rituximab, cyclophosphamide, liposome-encapsulated doxorubicin citrate
- Keywords
- contiguous stage II adult diffuse large cell lymphoma, 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.
filgrastimBiological
Given subcutaneously
pegfilgrastimBiological
Given subcutaneously
rituximabBiological
Given IV
cyclophosphamideDrug
Given IV
liposome-encapsulated doxorubicin citrateDrug
Given IV
prednisoneDrug
Given orally
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Arm I (R-COP regimen) | Experimental | Patients receive rituximab IV, cyclophosphamide IV, and vincristine sulfate IV on day 1. Patients also receive oral prednisone on days 1-5 and filgrastim subcutaneously (SC) on days 8-14 or pegfilgrastim SC on day 2. Treatment repeats every 21 days for at least 3 courses. Receives: Biological: filgrastim; Biological: pegfilgrastim; Biological: rituximab; Drug: cyclophosphamide; Drug: prednisone; Drug: vincristine sulfate |
| Arm II (R-COPY regimen) | Experimental | Patients receive rituximab, cyclophosphamide, vincristine sulfate, prednisone, and filgrastim or pegfilgrastim as in arm I. Patients also receive liposome-encapsulated doxorubicin citrate IV on day 1. Treatment repeats every 21 days for at least 3 courses. Receives: Biological: filgrastim; Biological: pegfilgrastim; Biological: rituximab; Drug: cyclophosphamide; Drug: liposome-encapsulated doxorubicin citrate; Drug: prednisone; Drug: vincristine sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants in Complete Remission 6 Months After Randomization
Complete remission [CR] is defined according to Cheson criteria. CR requires the following:
- Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities.
- All lymph nodes and nodal masses must have regressed to normal size. Previously involved nodes that were 1.1 to 1.5 cm in their greatest transverse diameter before treatment must have decreased to ≤1 cm in their greatest transverse diameter after treatment, or by more than 75% in the sum of the products of the greatest diameters (SPD).
- The spleen, if considered to be enlarged before therapy on the basis of a CT scan, must have regressed in size and must not be palpable on physical examination.
- If the bone marrow was involved by lymphoma before treatment, the infiltrate must be cleared on repeat bone marrow aspirate and biopsy of the same site.
Measured: 6 months after randomization
Number of Participants With Severe Toxicity
Severe toxicity, defined as febrile neutropenia or toxic death. Febrile neutropenia is defined in the International CTC toxicity scale as "fever of unknown origin without clinically or microbiologically documented infection: neutrophils < 1.0 x 109/l and fever ≥ 38.5° C.
Toxic death is defined as any death which occur during treatment (from day 1 of the first cycle of chemotherapy up to day 30 of the last cycle) and is not related to lymphoma.
Measured: 6 months after randomization
Secondary outcomes (2)
Overall Survival Time
OS is defined as the delay between the date of randomization and the date of death
Measured: from randomization, up to 5 years
Progression-free Survival Time
Delay between the date of randomization and the date of progression or death. Progression is defined according to the Cheson criteria.
Measured: from randomization, up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2009 (estimated)
- Study start2 Dec 2008
- Primary completion31 Dec 2012
- Study completion1 Jan 2015
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.
- 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomized non-comparative phase II trial
- Masking
- None (open label)
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut Bergonié
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute, France
- Responsible party
- Sponsor
- Investigators
- Pierre Soubeyran, MD, PhD, Principal investigator, Institut Bergonié
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00911183
- Sponsor's protocol ID
- IB-2008-25
- Other IDs
- IB-FRAIL06, INCA-RECF0892, EUDRACT-2008-001506-16
- Acronym
- FRAIL-06
- Status last verified
- Mar 2022
- First submitted
- 29 May 2009
- Last updated
- 29 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diffuse Large B Cell Non-Hodgkin's Lymphoma in the Vulnerable/Frail Elderly. A Multicentric Randomized Phase II Trial With Emphasis on Geriatric Assessment and Quality of Life
- ClinicalTrials.gov ID
- NCT00911183
- Acronym / sponsor ID
- FRAIL-06 / IB-2008-25
- Conditions
- Lymphoma
- Keywords
- contiguous stage II adult diffuse large cell lymphoma, 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
- 67 participants (actual)
- Lead sponsor
- Institut BergoniéUniversity, hospital or other
- Collaborators
- National Cancer Institute, France
- Study start
- 2 Dec 2008 (actual)
- Primary completion
- 31 Dec 2012 (actual)
- Study completion
- 1 Jan 2015 (actual)
- First posted
- 1 Jun 2009 (estimated)
- Results
- Posted 14 Jun 2022
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, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, prednisone, and liposome-encapsulated doxorubicin citrate, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It is not yet known whether rituximab and combination chemotherapy are more effective when given together with or without liposome-encapsulated doxorubicin citrate in treating older patients with diffuse large B-cell non-Hodgkin lymphoma.
PURPOSE: This randomized phase II trial is studying the side effects of giving rituximab together with cyclophosphamide, vincristine sulfate, and prednisone with or without liposome-encapsulated doxorubicin citrate and to see how well it works in treating older patients with stage II, stage III, or stage IV diffuse large B-cell non-Hodgkin lymphoma.
Detailed description
OBJECTIVES:
Primary
- To assess the therapeutic efficacy of rituximab, cyclophosphamide, vincristine sulfate, and prednisone with vs without liposome-encapsulated doxorubicin citrate, in terms of complete remission rate at 6 months, in vulnerable or frail elderly patients with stage II, III, or IV diffuse large B-cell non-Hodgkin lymphoma.
- To assess the safety of these regimens in these patients.
Secondary
- To evaluate the progression-free survival, event-free survival, and overall survival rates at 6 and 24 months in patients treated with these regimens.
- To evaluate the overall response rate at 6 and 24 months in patients treated with these regimens.
- To evaluate the duration of complete remission in patients treated with these regimens.
- To evaluate the acute side effects (according to the International CTC scale) of these regimens in these patients.
- To evaluate the geriatric condition and quality of life of patients treated with these regimens.
OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.
- Arm I (R-COP regimen): Patients receive rituximab IV, cyclophosphamide IV, and vincristine sulfate IV on day 1. Patients also receive oral prednisone on days 1-5 and filgrastim subcutaneously (SC) on days 8-14 or pegfilgrastim SC on day 2. Treatment repeats every 21 days for at least 3 courses.
- Arm II (R-COPY regimen): Patients receive rituximab, cyclophosphamide, vincristine sulfate, prednisone, and filgrastim or pegfilgrastim as in arm I. Patients also receive liposome-encapsulated doxorubicin citrate IV on day 1. Treatment repeats every 21 days for at least 3 courses.
After 3 courses of R-COP or R-COPY, patients undergo evaluation. Patients with disease progression or a response of < 25% are removed from the study. Patients with a response of ≥ 25% receive 3 more courses of R-COP or R-COPY, followed by rituximab IV alone on day 1 of courses 7 and 8 in the absence of disease progression or unacceptable toxicity.
After the completion of chemotherapy, some patients may undergo radiotherapy.
Patients complete quality of life and geriatric assessment questionnaires at baseline and periodically during study treatment.
After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- randomized non-comparative phase II trial
| Arm | Type | Receives |
|---|---|---|
| Arm I (R-COP regimen) | Experimental | Biological: filgrastim, Biological: pegfilgrastim, Biological: rituximab, Drug: cyclophosphamide, Drug: prednisone, Drug: vincristine sulfatePatients receive rituximab IV, cyclophosphamide IV, and vincristine sulfate IV on day 1. Patients also receive oral prednisone on days 1-5 and filgrastim subcutaneously (SC) on days 8-14 or pegfilgrastim SC on day 2. Treatment repeats every 21 days for at least 3 courses. |
| Arm II (R-COPY regimen) | Experimental | Biological: filgrastim, Biological: pegfilgrastim, Biological: rituximab, Drug: cyclophosphamide, Drug: liposome-encapsulated doxorubicin citrate, Drug: prednisone, Drug: vincristine sulfatePatients receive rituximab, cyclophosphamide, vincristine sulfate, prednisone, and filgrastim or pegfilgrastim as in arm I. Patients also receive liposome-encapsulated doxorubicin citrate IV on day 1. Treatment repeats every 21 days for at least 3 courses. |
Who may qualify
- Ages
- 70 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- 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 |
|---|---|---|
| filgrastimGiven subcutaneously | Biological | Arm I (R-COP regimen), Arm II (R-COPY regimen) |
| pegfilgrastimGiven subcutaneously | Biological | Arm I (R-COP regimen), Arm II (R-COPY regimen) |
| rituximabGiven IV | Biological | Arm I (R-COP regimen), Arm II (R-COPY regimen) |
| cyclophosphamideGiven IV | Drug | Arm I (R-COP regimen), Arm II (R-COPY regimen) |
| liposome-encapsulated doxorubicin citrateGiven IV | Drug | Arm II (R-COPY regimen) |
| prednisoneGiven orally | Drug | Arm I (R-COP regimen), Arm II (R-COPY regimen) |
| vincristine sulfateGiven IV | Drug | Arm I (R-COP regimen), Arm II (R-COPY regimen) |
Primary outcome
Number of Participants in Complete Remission 6 Months After Randomization
Time frame: 6 months after randomization
Complete remission [CR] is defined according to Cheson criteria. CR requires the following: 1. Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities. 2. All lymph nodes and nodal masses must have regressed to normal size. Previously involved nodes that were 1.1 to 1.5 cm in their greatest transverse diameter before treatment must have decreased to ≤1 cm in their greatest transverse diameter after treatment, or by more than 75% in the sum of the products of the greatest diameters (SPD). 3. The spleen, if considered to be enlarged before therapy on the basis of a CT scan, must have regressed in size and must not be palpable on physical examination. 4. If the bone marrow was involved by lymphoma before treatment, the infiltrate must be cleared on repeat bone marrow aspirate and biopsy of the same site.
Number of Participants With Severe Toxicity
Time frame: 6 months after randomization
Severe toxicity, defined as febrile neutropenia or toxic death. Febrile neutropenia is defined in the International CTC toxicity scale as "fever of unknown origin without clinically or microbiologically documented infection: neutrophils < 1.0 x 109/l and fever ≥ 38.5° C. Toxic death is defined as any death which occur during treatment (from day 1 of the first cycle of chemotherapy up to day 30 of the last cycle) and is not related to lymphoma.
2 secondary outcomes
Overall Survival Time
Time frame: from randomization, up to 5 years
Progression-free Survival Time
Time frame: from randomization, up to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Pierre Soubeyran, MD, PhD principal investigator
Institut Bergonié
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing filgrastim, pegfilgrastim and rituximab in people with Lymphoma, run by Institut Bergonié at 1 site in France.
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 29 Aug 2025. 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 France. 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 14 Jun 2022). 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?
Number of Participants in Complete Remission 6 Months After Randomization (time frame: 6 months after randomization). 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?
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 29 Aug 2025.