Lymphocytic Leukemia, ChronicPhase 2NCT02533401

A Study of Rituximab (MabThera) in Participants With Chronic Lymphocytic Leukemia (CLL)

A Phase 2 study testing Cyclophosphamide, Fludarabine and Rituximab in people with Lymphocytic Leukemia, Chronic, run by Hoffmann-La Roche at 9 sites in 2 countries.

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

This study will evaluate the efficacy and safety of rituximab in combination with chemotherapy (fludarabine and cyclophosphamide) in participants with B-cell CLL. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Lymphocytic Leukemia, Chronic
What is being tested?: Cyclophosphamide, Fludarabine and Rituximab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 34 participants
Where: 9 sitesin 2 countries
Study dates: Feb 2006to Dec 2014
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

Adult participants greater than or equal to (≥) 18 years of age
B-cell CLL
No previous treatment for leukemia

Who cannot join

History of other malignancies within 2 years before study entry, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, prostate cancer, or breast cancer
Comorbid condition requiring long-term (greater than [>] 1 month) systemic corticosteroids during study treatment
Known infection with hepatitis B or C virus or with human immunodeficiency virus (HIV)

Trial locations and contacts

9 sites in 2 countries.

Country

City, postcode or hospital

9 sites in 2 countries

Argentina8 sites

Study site
Buenos Aires, 1406
Study site
Buenos Aires, C1114AAN
Study site
Buenos Aires, C1280AEB
Study site
Buenos Aires, C1431FWO
Study site
Córdoba, 5016
Study site
La Plata, B1897GOL
Study site
Pilar, B1629ODT
Study site
Rosario, S2000DSV

Other trials in Argentina

Venezuela1 site

Study site
Caracas, 2122

Other trials in Venezuela

About this study

Official title: A Multicenter, Single-Arm, Phase II Study to Evaluate the Efficacy and Safety of Rituximab Plus Fludarabine and Cyclophosphamide (FCR) as First-Line Treatment in Patients With B-Cell Chronic Lymphocytic Leukemia (CLL)

This study will evaluate the efficacy and safety of rituximab in combination with chemotherapy (fludarabine and cyclophosphamide) in participants with B-cell CLL.

Conditions: Lymphocytic Leukemia, Chronic
Being tested: 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.

CyclophosphamideDrug
Cyclophosphamide will be administered IV at 250 mg/m^2/day on Day 2-4 of Cycle 1 and then on Day 1-3 of Cycles 2 to 6. Each cycle will be 28 days or 4 weeks in length.
FludarabineDrug
Fludarabine will be administered IV at 25 mg/m^2/day on Day 2-4 of Cycle 1 and then on Day 1-3 of Cycles 2 to 6. Each cycle will be 28 days or 4 weeks in length.
RituximabDrug
Also called MabThera/Rituxan
Rituximab will be administered IV at 375 mg/m^2 on Day 1 of Cycle 1 and then at 500 mg/m^2 on Day 1 of Cycles 2 to 6. Each cycle will be 28 days or 4 weeks in length.

Study groups in NCT02533401
Study group	Role	What they receive
Rituximab + Fludarabine + Cyclophosphamide	Experimental	Participants will receive rituximab (375 milligrams per meter-squared [mg/m^2] intravenously [IV]) on Cycle 1 Day 1, followed by fludarabine (25 mg/m^2 once daily IV) and cyclophosphamide (250 mg/m^2 once daily IV) for Days 2 to 4 of Cycle 1. Then rituximab (500 mg/m^2 IV) will be administered on Day 1 of Cycles 2 to 6, followed by IV fludarabine (25 mg/m^2 once daily IV) and cyclophosphamide (250 mg/m^2 once daily IV) on Days 1 to 3 of Cycles 2 to 6. Each cycle will be 28 days or 4 weeks in length, and the overall duration of treatment will be approximately 6 months. Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Rituximab

What is being measured

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

Percentage of Participants With Death or Disease Progression
Treatment response was monitored throughout the study and assessed using standardized criteria. Disease progression was defined as the occurrence of at least one of the following: greater than or equal to (≥) 50 percent (%) increase in the longest diameter of at least two enlarged lymph nodes, increase in spleen and/or liver size by at least 2 centimeters (cm) from Baseline as determined by measurement below the costal margin, or ≥50% increase in the number of circulating lymphocytes. The percentage of participants with death or documented disease progression at any time during the study was calculated.
Measured: Up to 5 years (from Baseline until disease progression or death, whichever occurred first)
Progression-Free Survival (PFS)
Treatment response was monitored throughout the study and assessed using standardized criteria. Disease progression was defined as the occurrence of at least one of the following: ≥50% increase in the longest diameter of at least two enlarged lymph nodes, increase in spleen and/or liver size by at least 2 cm from Baseline as determined by measurement below the costal margin, or ≥50% increase in the number of circulating lymphocytes. PFS was defined as the time from study inclusion until first event of disease progression or death and was estimated using Kaplan-Meier analysis.
Measured: Up to 5 years (from Baseline until disease progression or death, whichever occurred first)
Percentage of Participants Who Died
Participants were followed for survival throughout the study. The percentage of participants who died of any cause during the study was calculated.
Measured: Up to 5 years (from Baseline until death)
Overall Survival (OS)
Participants were followed for survival throughout the study. OS was defined as the time from study inclusion until death from any cause and was estimated using Kaplan-Meier analysis
Measured: Up to 5 years (from Baseline until death)
Percentage of Participants With Complete Response (CR), Nodular Partial Response (nPR), or Partial Response (PR)
Treatment response was monitored throughout the study and assessed using standardized criteria. CR was defined as hemoglobin ≥11 grams per deciliter (g/dL), lymphocytes less than (<) 4000 cells per cubic millimeter (cells/mm^3), neutrophils greater than (>) 1500 cells/mm^3, platelets >100,000 cells/mm^3, bone marrow (BM) biopsy with <30% lymphocytes with no lymphocytic infiltrates, no evidence of lymphoid nodules on physical exam, and performance status of 0. PR was defined as >50% decrease in size of enlarged lymph nodes, hepatomegaly, and splenomegaly, with peripheral counts meeting the same criteria as CR or ≥50% improvement from pre-treatment values. Participants with lymphoid nodules on BM biopsy who otherwise met CR criteria were considered nPR. The percentage of participants with each level of best overall response was calculated.
Measured: Up to 4 years (assessed every 3 months during 6-month treatment period, every 2 months during 6-month safety follow-up, then every 3 months during 3-year safety follow-up)

Timeline

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

Feb 2006Dec 2014

First posted26 Aug 2015 (estimated)
Study startFeb 2006
Primary completionDec 2014
Study completionDec 2014

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 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 34 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02533401
Sponsor's protocol ID: ML18429
Status last verified: Mar 2016
First submitted: 24 Aug 2015
Last updated: 2 May 2016
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Not yet recruitingPhase 2
Nemtabrutinib for Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL) Refractory to Covalent Bruton Tyrosine Kinase Inhibitor or Pirtobrutinib and Previously Treated With a BCL2 Inhibitor
Chronic Lymphocytic Leukemia, Small Lymphocytic Leukemia
RecruitingObservational study
Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)
Waldenstrom Macroglobulinemia, Lymphoplasmacytic Lymphoma
RecruitingPhase 3
A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010).
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Chronic Lymphocytic

All Lymphocytic Leukemia, Chronic trials

Study at a glance

From the registry record, last updated by the sponsor on 2 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Single-Arm, Phase II Study to Evaluate the Efficacy and Safety of Rituximab Plus Fludarabine and Cyclophosphamide (FCR) as First-Line Treatment in Patients With B-Cell Chronic Lymphocytic Leukemia (CLL)
ClinicalTrials.gov ID: NCT02533401
Acronym / sponsor ID: ML18429
Conditions: Lymphocytic Leukemia, Chronic
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 34 participants (actual)
Lead sponsor: Hoffmann-La RocheIndustry (pharma, biotech, devices)
Study start: Feb 2006
Primary completion: Dec 2014 (actual)
Study completion: Dec 2014 (actual)
First posted: 26 Aug 2015 (estimated)
Results: Posted 2 May 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study will evaluate the efficacy and safety of rituximab in combination with chemotherapy (fludarabine and cyclophosphamide) in participants with B-cell CLL.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Rituximab + Fludarabine + Cyclophosphamide	Experimental	Drug: Cyclophosphamide, Drug: Fludarabine, Drug: RituximabParticipants will receive rituximab (375 milligrams per meter-squared [mg/m^2] intravenously [IV]) on Cycle 1 Day 1, followed by fludarabine (25 mg/m^2 once daily IV) and cyclophosphamide (250 mg/m^2 once daily IV) for Days 2 to 4 of Cycle 1. Then rituximab (500 mg/m^2 IV) will be administered on Day 1 of Cycles 2 to 6, followed by IV fludarabine (25 mg/m^2 once daily IV) and cyclophosphamide (250 mg/m^2 once daily IV) on Days 1 to 3 of Cycles 2 to 6. Each cycle will be 28 days or 4 weeks in length, and the overall duration of treatment will be approximately 6 months.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Adult participants greater than or equal to (≥) 18 years of age
B-cell CLL
No previous treatment for leukemia

Key exclusion criteria (3 listed)

History of other malignancies within 2 years before study entry, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, prostate cancer, or breast cancer
Comorbid condition requiring long-term (greater than [>] 1 month) systemic corticosteroids during study treatment
Known infection with hepatitis B or C virus or with human immunodeficiency virus (HIV)

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
CyclophosphamideCyclophosphamide will be administered IV at 250 mg/m^2/day on Day 2-4 of Cycle 1 and then on Day 1-3 of Cycles 2 to 6. Each cycle will be 28 days or 4 weeks in length.	Drug	Rituximab + Fludarabine + Cyclophosphamide
FludarabineFludarabine will be administered IV at 25 mg/m^2/day on Day 2-4 of Cycle 1 and then on Day 1-3 of Cycles 2 to 6. Each cycle will be 28 days or 4 weeks in length.	Drug	Rituximab + Fludarabine + Cyclophosphamide
RituximabAlso: MabThera/RituxanRituximab will be administered IV at 375 mg/m^2 on Day 1 of Cycle 1 and then at 500 mg/m^2 on Day 1 of Cycles 2 to 6. Each cycle will be 28 days or 4 weeks in length.	Drug	Rituximab + Fludarabine + Cyclophosphamide

Primary outcome

Percentage of Participants With Death or Disease Progression
Time frame: Up to 5 years (from Baseline until disease progression or death, whichever occurred first)
Treatment response was monitored throughout the study and assessed using standardized criteria. Disease progression was defined as the occurrence of at least one of the following: greater than or equal to (≥) 50 percent (%) increase in the longest diameter of at least two enlarged lymph nodes, increase in spleen and/or liver size by at least 2 centimeters (cm) from Baseline as determined by measurement below the costal margin, or ≥50% increase in the number of circulating lymphocytes. The percentage of participants with death or documented disease progression at any time during the study was calculated.
Progression-Free Survival (PFS)
Time frame: Up to 5 years (from Baseline until disease progression or death, whichever occurred first)
Treatment response was monitored throughout the study and assessed using standardized criteria. Disease progression was defined as the occurrence of at least one of the following: ≥50% increase in the longest diameter of at least two enlarged lymph nodes, increase in spleen and/or liver size by at least 2 cm from Baseline as determined by measurement below the costal margin, or ≥50% increase in the number of circulating lymphocytes. PFS was defined as the time from study inclusion until first event of disease progression or death and was estimated using Kaplan-Meier analysis.
Percentage of Participants Who Died
Time frame: Up to 5 years (from Baseline until death)
Participants were followed for survival throughout the study. The percentage of participants who died of any cause during the study was calculated.
Overall Survival (OS)
Time frame: Up to 5 years (from Baseline until death)
Participants were followed for survival throughout the study. OS was defined as the time from study inclusion until death from any cause and was estimated using Kaplan-Meier analysis
Percentage of Participants With Complete Response (CR), Nodular Partial Response (nPR), or Partial Response (PR)
Time frame: Up to 4 years (assessed every 3 months during 6-month treatment period, every 2 months during 6-month safety follow-up, then every 3 months during 3-year safety follow-up)
Treatment response was monitored throughout the study and assessed using standardized criteria. CR was defined as hemoglobin ≥11 grams per deciliter (g/dL), lymphocytes less than (<) 4000 cells per cubic millimeter (cells/mm^3), neutrophils greater than (>) 1500 cells/mm^3, platelets >100,000 cells/mm^3, bone marrow (BM) biopsy with <30% lymphocytes with no lymphocytic infiltrates, no evidence of lymphoid nodules on physical exam, and performance status of 0. PR was defined as >50% decrease in size of enlarged lymph nodes, hepatomegaly, and splenomegaly, with peripheral counts meeting the same criteria as CR or ≥50% improvement from pre-treatment values. Participants with lymphoid nodules on BM biopsy who otherwise met CR criteria were considered nPR. The percentage of participants with each level of best overall response was calculated.

Results and safety

Results posted to the registry on 2 May 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Rituximab + Fludarabine + Cyclophosphamide	34	23

Primary outcome: Percentage of Participants With Death or Disease Progression

Time frame: Up to 5 years (from Baseline until disease progression or death, whichever occurred first). Number. Unit: percentage of participants

Measure	Rituximab + Fludarabine + Cyclophosphamide n = 34
Value	24

Population analysed: All Participants Enrolled.

Primary outcome: Progression-Free Survival (PFS)

Time frame: Up to 5 years (from Baseline until disease progression or death, whichever occurred first). Mean (95% Confidence Interval). Unit: months

Measure	Rituximab + Fludarabine + Cyclophosphamide n = 34
Value	47.2 (42.2 to 52.2)

Population analysed: All Participants Enrolled.

Primary outcome: Percentage of Participants Who Died

Time frame: Up to 5 years (from Baseline until death). Number. Unit: percentage of participants

Measure	Rituximab + Fludarabine + Cyclophosphamide n = 34
Value	14

Population analysed: All Participants Enrolled.

Primary outcome: Overall Survival (OS)

Time frame: Up to 5 years (from Baseline until death). Mean (95% Confidence Interval). Unit: months

Measure	Rituximab + Fludarabine + Cyclophosphamide n = 34
Value	49.5 (44.8 to 54.2)

Population analysed: All Participants Enrolled.

Adverse events

Time frame: Up to 4 years (assessed every 4 weeks during 6-month treatment period, every 2 months during 6-month safety follow-up, then every 3 months during 3-year safety follow-up. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Rituximab + Fludarabine + Cyclophosphamide	15 of 34 (44.1%)	18 of 34 (52.9%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Lymphocytic Leukemia, Chronic

RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
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Not yet recruitingPhase 2
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RecruitingObservational study
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RecruitingPhase 3
A Study of Nemtabrutinib Plus Venetoclax vs Venetoclax + Rituximab (VR) in Second-line (2L) + Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (MK-1026-010/BELLWAVE-010).
Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Chronic Lymphocytic

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 chair

Hoffmann-La Roche

9 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cyclophosphamide, Fludarabine and Rituximab in people with Lymphocytic Leukemia, Chronic, run by Hoffmann-La Roche at 9 sites in 2 countries.

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 3 inclusion and 3 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 2 May 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Argentina, Venezuela. 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 2 May 2016). 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 Death or Disease Progression (time frame: Up to 5 years (from Baseline until disease progression or death, whichever occurred first)). The study lists 5 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 NCT02533401.

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 2 May 2016.