Lymphocytic Leukemia, ChronicPhase 4NCT01283386
A Study to Compare Mabthera (Rituximab), Fludarabine and Cyclophosphamide to Mabthera and Chlorambucil in Participants With Chronic Lymphocytic Leukemia and Unfavorable Somatic Status
A Phase 4 study testing Chlorambucil, Cyclophosphamide and Fludarabine in people with Lymphocytic Leukemia, Chronic, run by Hoffmann-La Roche at 8 sites in Russia.
Trial summary
This multi-center, randomized study compared the efficacy and safety of MabThera (rituximab) in combination with either fludarabine and cyclophosphamide or with chlorambucil in participants with previously untreated B-cell chronic lymphocytic leukemia and unfavorable somatic status. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Lymphocytic Leukemia, Chronic
- What is being tested?
- Chlorambucil, Cyclophosphamide and Fludarabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 8 sitesRussia
- Study dates
- 27 Apr 2011to 16 Mar 2016
- Phase
- Phase 4
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients, 60-70 or >70 years of age
- Cumulative Illness Rating Scale (CIRS) comorbidity score >/=7 if patient is 60-70 years old
- Previously untreated B-cell chronic lymphocytic leukemia
- Binet stage B, C or A with progression
- ECOG performance status 0-2
Who cannot join
- Small-cell lymphoma
- Autoimmune hemolytic anemia
- Concomitant malignant disease during enrollment, except for basal cell carcinoma of the skin
- Chemotherapy for concomitant malignant disease within 12 months prior to study enrollment
- Richter's syndrome
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Russia8 sites
The order of Honour pin Irkutsk regional clinical hospital; Hematology Department
Irkutsk, 664079
Kemerovo Regional Clinical Hospital
Kemerovo, 650066
N.N.Blokhin Russian Cancer Research Center; Dept. of Chemotherapy & Hemoblastosis
Moscow, 115478
City Clinical Botkin's Hospital; City Hematological Center
Moscow, 125284
Saint-Petersburg SHI City Clinical Hospital #31
Saint Petersburg, 197110
City Clinical Hospital #15; Hematology department
Saint Petersburg, 198205
GUZ Tula Regioanal Clinical Hospital; Hematology
Tula, 300053
Republican clinical hospital named after G.G. Kuvatov
Ufa, 450005
About this study
Official title: Prospective Randomized Study to Compare Efficacy and Safety of RFC-Lite (Rituximab, Fludarabine, Cyclophosphamide) Regimen With LR (Rituximab, Chlorambucil) as a First-Line Therapy in Patients With B-Cell Chronic Lymphocytic Leukemia and Unfavorable Somatic Status
This multi-center, randomized study compared the efficacy and safety of MabThera (rituximab) in combination with either fludarabine and cyclophosphamide or with chlorambucil in participants with previously untreated B-cell chronic lymphocytic leukemia and unfavorable somatic status. Participants were randomized to receive Mabthera (375 mg/m2 intravenously [IV] Day 1 of Cycle 1, 500 mg/m2 IV Day 1 Cycles 2-6) with either fludarabine (20 mg/m2 IV or 32 mg/m2 orally Days 1-3) and cyclophosphamide (150 mg/m2 IV or orally Days 1-3) or with chlorambucil (10 mg/m2 orally Days 1-7) for 6 cycles of 28 days. Anticipated time on study treatment was 24 weeks.
- Conditions
- Lymphocytic Leukemia, Chronic
- Being tested
- Chlorambucil, Cyclophosphamide, Fludarabine, Rituximab
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChlorambucilDrug
10 mg/m^2 orally on Days 1-7 of each 28-day cycle for 6 cycles
CyclophosphamideDrug
150 mg/m^2 IV or orally on Days 1-3 of each 28-day cycle for 6 cycles
FludarabineDrug
20 mg/m^2 IV or 32 mg/m2 orally Days 1-3 of each 28-day cycle for 6 cycles
RituximabDrug
Also called MabThera
375 mg/m2 IV on Day 1 of Cycle 1; 500 mg/m2 IV on Day 1 of Cycles 2-6 (28-day cycles)
| Study group | Role | What they receive |
|---|---|---|
| FCR-lite | Experimental | Rituximab, fludarabine, and cyclophosphamide Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Rituximab |
| LR Therapy | Active comparator | Rituximab and chlorambucile Receives: Drug: Chlorambucil; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Complete Remission
Complete remission was defined as the disappearance of all signs of disease.
Measured: Up to approximately 5 years
Percentage of Participants With Disease Progression
Disease progression was defined as an increase in lymphocytosis, or enlargement of the lymph nodes or spleen.
Measured: Up to approximately 5 years
Percentage of Participants With Stable Disease
Stable disease was defined as not meeting the criteria for partial remission or disease progression
Measured: Up to approximately 5 years
Percentage of Participants With Partial Remission
Partial remission was defined as a reduction in tumor size by >50%.
Measured: Up to approximately 5 years
Duration of Response
Duration of Response was defined as the time period from the last day of study treatment to the day when disease progression occurred in participants who previously had complete or partial remission. Disease progression was defined as an increase in lymphocytosis, or enlargement of the lymph nodes or spleen. Complete remission was defined as the disappearance of all signs of disease. Partial remission was defined as a reduction in tumor size by >50%.
Measured: Up to approximately 5 years
Progression-free Survival
Progression-free survival was defined as the time period from the first day of study treatment to the day when disease progression occurred. Disease progression was defined as an increase in lymphocytosis, or enlargement of the lymph nodes or spleen.
Measured: Up to approximately 5 years
Event-free Survival
Event-free survival was defined as the time period from the first day of study treatment to occurrence of any of the following events: appearance of disease progression or relapse; prescription of a new treatment for disease relapse; death caused by B-cell chronic lymphocytic leukemia (B-CLL); or complications from B-CLL or therapy. Relapse was defined as disease progression in participants with complete or partial remission lasting at least 6 months after treatment completion. Disease progression was defined as an increase in lymphocytosis, or enlargement of the lymph nodes or spleen. Complete remission was defined as the disappearance of all signs of disease. Partial remission was defined as a reduction in tumor size by >50%.
Measured: Up to approximately 5 years
Overall Survival
Overall survival was defined as the time period from the first day of study treatment to participant death.
Measured: Up to approximately 5 years
Percentage of Participants With Phenotypic Remission
Phenotypic remission was considered achieved if a participant had a negative test for minimal residual disease. A negative test for minimal residual disease was defined as tumor cells ≤0.01% of the total number of peripheral leukocytes.
Measured: Up to approximately 5 years
Percentage of Participants With Adverse Events (AEs) and Serious AEs
An AE was defined as any unfavorable medical occurrence in a participant receiving a study drug, regardless of relationship the study drug. An AE was considered serious if it met any of the following criteria: was fatal or life-threatening; required hospitalization or prolonged hospitalization; led to persistent or significant disability/incapacity; was a congenital anomaly/birth defect; was clinically significant and/or required an intervention to prevent any of the listed criteria.
Measured: Up to approximately 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2011 (estimated)
- Study start27 Apr 2011
- Primary completion16 Mar 2016
- Study completion16 Mar 2016
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 Lymphocytic Leukemia, ChronicStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01283386
- Sponsor's protocol ID
- ML25137
- Status last verified
- Nov 2018
- First submitted
- 18 Jan 2011
- Last updated
- 14 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Randomized Study to Compare Efficacy and Safety of RFC-Lite (Rituximab, Fludarabine, Cyclophosphamide) Regimen With LR (Rituximab, Chlorambucil) as a First-Line Therapy in Patients With B-Cell Chronic Lymphocytic Leukemia and Unfavorable Somatic Status
- ClinicalTrials.gov ID
- NCT01283386
- Acronym / sponsor ID
- ML25137
- Conditions
- Lymphocytic Leukemia, Chronic
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 27 Apr 2011 (actual)
- Primary completion
- 16 Mar 2016 (actual)
- Study completion
- 16 Mar 2016 (actual)
- First posted
- 26 Jan 2011 (estimated)
- Results
- Posted 14 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This multi-center, randomized study compared the efficacy and safety of MabThera (rituximab) in combination with either fludarabine and cyclophosphamide or with chlorambucil in participants with previously untreated B-cell chronic lymphocytic leukemia and unfavorable somatic status. Participants were randomized to receive Mabthera (375 mg/m2 intravenously [IV] Day 1 of Cycle 1, 500 mg/m2 IV Day 1 Cycles 2-6) with either fludarabine (20 mg/m2 IV or 32 mg/m2 orally Days 1-3) and cyclophosphamide (150 mg/m2 IV or orally Days 1-3) or with chlorambucil (10 mg/m2 orally Days 1-7) for 6 cycles of 28 days. Anticipated time on study treatment was 24 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FCR-lite | Experimental | Drug: Cyclophosphamide, Drug: Fludarabine, Drug: RituximabRituximab, fludarabine, and cyclophosphamide |
| LR Therapy | Active comparator | Drug: Chlorambucil, Drug: RituximabRituximab and chlorambucile |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adult patients, 60-70 or >70 years of age
- Cumulative Illness Rating Scale (CIRS) comorbidity score >/=7 if patient is 60-70 years old
- Previously untreated B-cell chronic lymphocytic leukemia
- Binet stage B, C or A with progression
- ECOG performance status 0-2
Key exclusion criteria (5 listed)
- Small-cell lymphoma
- Autoimmune hemolytic anemia
- Concomitant malignant disease during enrollment, except for basal cell carcinoma of the skin
- Chemotherapy for concomitant malignant disease within 12 months prior to study enrollment
- Richter's syndrome
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 |
|---|---|---|
| Chlorambucil10 mg/m^2 orally on Days 1-7 of each 28-day cycle for 6 cycles | Drug | LR Therapy |
| Cyclophosphamide150 mg/m^2 IV or orally on Days 1-3 of each 28-day cycle for 6 cycles | Drug | FCR-lite |
| Fludarabine20 mg/m^2 IV or 32 mg/m2 orally Days 1-3 of each 28-day cycle for 6 cycles | Drug | FCR-lite |
| RituximabAlso: MabThera375 mg/m2 IV on Day 1 of Cycle 1; 500 mg/m2 IV on Day 1 of Cycles 2-6 (28-day cycles) | Drug | FCR-lite, LR Therapy |
Primary outcome
Percentage of Participants With Complete Remission
Time frame: Up to approximately 5 years
Complete remission was defined as the disappearance of all signs of disease.
Percentage of Participants With Disease Progression
Time frame: Up to approximately 5 years
Disease progression was defined as an increase in lymphocytosis, or enlargement of the lymph nodes or spleen.
Percentage of Participants With Stable Disease
Time frame: Up to approximately 5 years
Stable disease was defined as not meeting the criteria for partial remission or disease progression
Percentage of Participants With Partial Remission
Time frame: Up to approximately 5 years
Partial remission was defined as a reduction in tumor size by >50%.
Duration of Response
Time frame: Up to approximately 5 years
Duration of Response was defined as the time period from the last day of study treatment to the day when disease progression occurred in participants who previously had complete or partial remission. Disease progression was defined as an increase in lymphocytosis, or enlargement of the lymph nodes or spleen. Complete remission was defined as the disappearance of all signs of disease. Partial remission was defined as a reduction in tumor size by >50%.
Progression-free Survival
Time frame: Up to approximately 5 years
Progression-free survival was defined as the time period from the first day of study treatment to the day when disease progression occurred. Disease progression was defined as an increase in lymphocytosis, or enlargement of the lymph nodes or spleen.
Event-free Survival
Time frame: Up to approximately 5 years
Event-free survival was defined as the time period from the first day of study treatment to occurrence of any of the following events: appearance of disease progression or relapse; prescription of a new treatment for disease relapse; death caused by B-cell chronic lymphocytic leukemia (B-CLL); or complications from B-CLL or therapy. Relapse was defined as disease progression in participants with complete or partial remission lasting at least 6 months after treatment completion. Disease progression was defined as an increase in lymphocytosis, or enlargement of the lymph nodes or spleen. Complete remission was defined as the disappearance of all signs of disease. Partial remission was defined as a reduction in tumor size by >50%.
Overall Survival
Time frame: Up to approximately 5 years
Overall survival was defined as the time period from the first day of study treatment to participant death.
Percentage of Participants With Phenotypic Remission
Time frame: Up to approximately 5 years
Phenotypic remission was considered achieved if a participant had a negative test for minimal residual disease. A negative test for minimal residual disease was defined as tumor cells ≤0.01% of the total number of peripheral leukocytes.
Percentage of Participants With Adverse Events (AEs) and Serious AEs
Time frame: Up to approximately 5 years
An AE was defined as any unfavorable medical occurrence in a participant receiving a study drug, regardless of relationship the study drug. An AE was considered serious if it met any of the following criteria: was fatal or life-threatening; required hospitalization or prolonged hospitalization; led to persistent or significant disability/incapacity; was a congenital anomaly/birth defect; was clinically significant and/or required an intervention to prevent any of the listed criteria.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2019.
- 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.
Clinical Trials study director
Hoffmann-La Roche
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Chlorambucil, Cyclophosphamide and Fludarabine in people with Lymphocytic Leukemia, Chronic, run by Hoffmann-La Roche at 8 sites in Russia.
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 5 inclusion and 5 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 14 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Russia. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Mar 2019). 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?
Percentage of Participants With Complete Remission (time frame: Up to approximately 5 years). The study lists 10 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 14 Mar 2019.