Leukemia, Lymphocytic, Chronic, B-CellPhase 2NCT00545714
A Study to Assess the Efficacy of Rituximab (MabThera) in First Line Treatment of Chronic Lymphocytic Leukemia (CLL)
A Phase 2 study testing Cyclophosphamide, Fludarabine and Rituximab in people with Leukemia, Lymphocytic, Chronic, B-Cell, run by Hoffmann-La Roche at 33 sites in Spain.
Trial summary
This single arm study will assess the efficacy and safety of rituximab in combination with fludarabine and cyclophosphamide, followed by rituximab maintenance therapy, as first line treatment of participants with CLL. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Leukemia, Lymphocytic, Chronic, B-Cell
- 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
- 86 participants
- Where
- 33 sitesSpain
- Study dates
- 21 Nov 2007to 20 May 2016
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- CLL according to World Health Organization diagnostic criteria
- Active disease
- No previous treatment
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Who cannot join
- Transformation to aggressive B-cell malignancy (prolymphocytic leukemia, large-cell lymphoma, Hodgkin's lymphoma)
- Other malignancies except for localized skin cancer
- Continuous systemic corticosteroid treatment
- Known infection with hepatitis B or C
Trial locations and contacts
33 sites in 1 country.
33 sites in 1 country
Spain33 sites
Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Hematologia
A Coruña, LA Coruña, 15006
Fundacion Hospital de Alcorcon; Servicio de Hematologia
Alcorcón, Madrid, 28922
Hospital Universitario Infanta Cristina; Servicio de Hematologia
Badajoz, 06080
Hospital Duran i Reynals; Servicio de Hematologia
Barcelona, 08907
Hospital de Basurto; Servicio de Hematologia
Bilbao, Vizcaya, 48013
Hospital San Pedro De Alcantara; Servicio de Hematologia
Cáceres, 10003
Hospital Universitario Puerta del Mar; Servicio de Hematologia
Cadiz, Cadiz, 11009
Hospital General de Castellon; Servicio de Hematologia
Castellon, Castellon, 12004
Hospital Francesc de Borja; Servicio de Hematologia
Gandia, Valencia, 46702
Hospital Universitario Virgen de las Nieves; Servicio de Hematologia
Granada, 18014
Hospital de Jerez de la Frontera; Servicio de Hematologia
Jerez de la Frontera, Cadiz, 11407
Hospital General Universitario Gregorio Marañon; Servicio de Hematología
Madrid, 28007
Hospital Ramon y Cajal; Servicio de Hematologia
Madrid, 28034
Hospital Universitario Clínico San Carlos; Servicio de Hematología
Madrid, 28040
Hospital Univ. 12 de Octubre; Servicio de Hematologia
Madrid, 28041
Hospital Universitario la Paz; Servicio de Hematologia
Madrid, 28046
HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio Hematologia
Madrid, 28050
Hospital Universitario Puerta de Hierro; Servicio de Hematologia
Madrid, 28222
Hospital Universitario Principe de Asturias; Servicio de Hematología
Madrid, 28805
Hospital Universitario de Getafe; Servico de Hematologia
Madrid, 28905
Hospital Clinico Universitario Virgen de la Victoria; Servicio de Hematologia
Málaga, 29010
Hosital Universitario de Mostoles;Servicio de Hematologia
Móstoles, Madrid, 28935
Hospital General Universitario J.M Morales Meseguer; Servicio de Hematología
Murcia, 30008
Hospital de Sagunto; Servicio de Hematologia
Sagunto, Valencia, 46520
Hospital Clinico Universitario de Salamanca;Servicio de Hematologia
Salamanca, 37007
Hospital Universitario Marques de Valdecilla; Servicio de Hematologia
Santander, Cantabria, 39008
Hospital General Universitario de Valencia; Servicio de Hematologia
Valencia, 46014
Hospital Arnau de Vilanova (Valencia) Servicio de Hematologia
Valencia, 46015
Hospital Universitario Dr. Peset; Servicio de Hematologia
Valencia, 46017
Hospital Universitario la Fe; Servicio de Hematologia
Valencia, 46026
Hospital De Txagorritxu; Servicio de Hematologia
Vitoria-Gasteiz, Alava, 01009
Hospital Clinico Universitario Lozano Blesa; Servicio de Hematologia
Zaragoza, 50009
Hospital Universitario Miguel Servet; Servicio Hematologia
Zaragoza, 50009
About this study
Official title: Multicentre, Non-Randomised, Open-Label Phase II Study to Evaluate the Efficacy and Safety of Induction Treatment With Rituximab, Fludarabine, Cyclophosphamide, Followed by Rituximab Maintenance Therapy (R-Fc-Rm) in the First Line Treatment of Chronic Lymphocytic Leukaemia
This single arm study will assess the efficacy and safety of rituximab in combination with fludarabine and cyclophosphamide, followed by rituximab maintenance therapy, as first line treatment of participants with CLL.
- Conditions
- Leukemia, Lymphocytic, Chronic, B-Cell
- 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 250 mg/m^2 as IV infusion will be administered on Days 1-3 of first six 28-day cycles.
FludarabineDrug
Fludarabine 25 mg/m^2 as IV infusion will be administered on Days 1-3 of first six 28-day cycles.
RituximabDrug
Also called MabThera, Rituxan
Rituximab 375 mg/m^2 as IV infusion will be administered on Day 0 of Cycle 1; 500 mg/m^2 as IV infusion will be administered on Day 1 of Cycle 2-6; and 375 mg/m^2 as IV infusion every 2 months from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6.
| Study group | Role | What they receive |
|---|---|---|
| Rituximab + Fludarabine + Cyclophosphamide | Experimental | Participants will receive 6 cycles (cycle length = 28 days) of treatment with rituximab (375 milligrams per square meter [mg/m^2] as intravenous [IV] infusion on Day 0 of Cycle 1 and 500 mg/m^2 as IV infusion on Day 1 of Cycles 2-6); fludarabine (25 mg/m^2 on Days 1-3) and cyclophosphamide (250 mg/m^2 on Days 1-3). Participants with a partial or complete response and appropriate neutrophil conditions will receive maintenance treatment with rituximab (375 mg/m^2 as IV infusion every 2 months) from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6. 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 CR Achieved After the Rituximab, Fludarabine, and Cyclophosphamide Regimen
CR was defined as no adenopathies (ADPs) and visceromegalies (VSMs) in physical examination (PE); no general symptoms (Sx); lymphocytes (Lymph) in peripheral blood less than (<) 4000 per cubic millimeter (mm^3); normalization of peripheral blood parameters: neutrophils (Neut) greater than (>) 1500/mm^3, platelets (Plt) >100,000/mm^3, hemoglobin (Hb) >11 grams per deciliter (g/dL) without transfusion; normocellular bone marrow (BM) with <30% Lymph; BM aspirate/biopsy with no evidence of infiltration of lymphoid nodules.
Measured: Month 9
Secondary outcomes (13)
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
CR was defined as no ADPs and VSMs in PE; no general Sx; Lymph in peripheral blood <4000/mm^3; normalization of peripheral blood parameters: Neut >1500/mm^3, Plt >100,000/mm^3, Hb >11 g/dL without transfusion; normocellular BM with <30% Lymph; BM aspirate/biopsy with no evidence of infiltration of lymphoid nodules. PR was defined as decrease >50% in Lymph in peripheral blood; reduction in ADPs >50% in total sum of up to 6 ADPs or in the baseline ADP of largest diameter (LD), no new ADP or enlargement of a prior ADP; >50% decrease in VSM; Neut >1500/mm^3 or >50% increase from Baseline; Plt >100,000/mm^3 or >50% increase from Baseline; Hb >11.0 g/dL or >50% increase from Baseline value without transfusion. Participants who met all CR criteria but had persistent anemia or thrombocytopenia were considered as PR.
Measured: Post-Induction Phase (IP): at 6 months; during Maintenance Phase (MP): at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up (FU): at Follow-Up Months 6, 12, 18, 24, 30, 36
Percentage of Participants With Clinical Response of CR or PR Among Participants With Negative Minimal Residual Disease (MRD) as Assessed by Multiparameter Flow Cytometry
CR: no ADPs and VSMs in PE; no general Sx; Lymph in peripheral blood <4000/mm^3; normalization of peripheral blood parameters: Neut >1500/mm^3, Plt >100,000/mm^3, Hb >11 g/dL without transfusion; normocellular BM with <30% Lymph; BM aspirate/biopsy with no evidence of infiltration of lymphoid nodules. PR: decrease >50% in Lymph in peripheral blood; reduction in ADPs >50% in total sum of up to 6 ADPs or in the baseline ADP of largest diameter (LD), no new ADP or enlargement of a prior ADP; >50% decrease in VSM; Neut >1500/mm^3 or >50% increase from Baseline; Plt >100,000/mm^3 or >50% increase from Baseline; Hb >11.0 g/dL or >50% increase from Baseline value without transfusion. Participants who met all CR criteria but had persistent anemia or thrombocytopenia were considered as PR. Negative MRD: Lymph <0.01% of all white blood cells (WBCs) in blood or BM after two consecutive measurements. Analysis performed only in blood during the Maintenance Phase and Follow-Up.
Measured: Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up: at Follow-Up Months 6, 12, 18, 24, 36
Percentage of Participants With CR With Incomplete Bone Marrow Recovery (CRi)
Participants with CRi were those who met all CR criteria (including BM examinations) but had persistent anemia, thrombocytopenia, or neutropenia apparently unrelated to chronic lymphocytic leukemia (CLL) but related to drug toxicity. CR: no ADPs and VSMs in PE; no general Sx; Lymph in peripheral blood <4000/mm^3; normalization of peripheral blood parameters: Neut >1500/mm^3, Plt >100,000/mm^3, Hb >11 g/dL without transfusion; normocellular BM with <30% Lymph; BM aspirate/biopsy with no evidence of infiltration of lymphoid nodules.
Measured: Baseline up to progressive disease (PD) or death due to any cause, whichever occurred first (up to 92 months)
Percentage of Participants Who Died
Measured: Baseline up to death due to any cause (up to 92 months)
Overall Survival (OS)
OS was defined as time from treatment start to death of the participant. For all other participants, the last follow-up available was taken as the last control. If the participant had not completed the study, the date of the last visit available was considered. OS was estimated using Kaplan-Meier (KM) methodology.
Measured: Baseline up to death due to any cause (up to 92 months)
Percentage of Participants With PD or Death
PD was defined as new ADPs (1.5 centimeters [cm]), hepato-/splenomegaly (HSM), Richter syndrome (RS), or other infiltrated organs; greater than or equal to (>/=) 50% increase in size of Baseline prior ADPs or HSM in participants with PR; Lymph increase >/=50% in peripheral blood with B Lymph >/=5000/mm^3; cytopenia attributable to CLL. Progression of any cytopenia (not related to autoimmune cytopenia) reported as a 2-g/dL decrease in basal Hb, Hb <10 g/dL, >/=50% decrease in basal Plt count, or count <100,000/mm^3 at >/=3 months post-treatment was defined as PD if BM biopsy confirmed infiltration of clonal CLL cells.
Measured: Baseline up to PD or death due to any cause, whichever occurred first (up to 92 months)
Progression-Free Survival (PFS)
PFS was defined as time from start of study treatment to PD or death, whichever occurred first. For other participants, last follow-up available was taken as last control. If participant did not complete study, date of last visit available was considered. PFS was estimated using KM methodology. PD was defined as new ADPs (1.5 cm), HSM, RS, or other infiltrated organs; >/=50% increase in size of Baseline prior ADPs or HSM in participants with PR; Lymph increase >/=50% in peripheral blood with B Lymph >/=5000/mm^3; cytopenia attributable to CLL. Progression of any cytopenia (not related to autoimmune cytopenia) reported as a 2-g/dL decrease in basal Hb, Hb <10 g/dL, >/=50% decrease in basal Plt count, or count <100,000/mm^3 at >/=3 months post-treatment was defined as PD if BM biopsy confirmed infiltration of clonal CLL cells.
Measured: Baseline up to PD or death due to any cause, whichever occurred first (up to 92 months)
Treatment-Free Survival (TFS)
TFS was defined time from start of study treatment until participant received new chemotherapy/immunotherapy because of PD and to reduce the disease with palliative or curative intent. PD was defined as new ADPs (1.5 cm), HSM, RS, or other infiltrated organs; >/=50% increase in size of Baseline prior ADPs or HSM in participants with PR; Lymph increase >/=50% in peripheral blood with B Lymph >/=5000/mm^3; cytopenia attributable to CLL. Progression of any cytopenia (not related to autoimmune cytopenia) reported as a 2-g/dL decrease in basal Hb, Hb <10 g/dL, >/=50% decrease in basal Plt count, or count <100,000/mm^3 at >/=3 months post-treatment was defined as PD if BM biopsy confirmed infiltration of clonal CLL cells.
Measured: Baseline up to PD or death due to any cause, whichever occurred first (up to 92 months)
Duration of Response (DOR)
DOR: time from CR/PR to MRD/PD. PD: new ADP (1.5 cm), HSM, RS, other infiltrated organs or >/=50% increase size in those with PR; blood Lymph increase >/=50% with B Lymph >/=5000/mm^3; cytopenia due to CLL. Progression of (nonautoimmune) cytopenia: 2-g/dL decrease basal Hb, Hb <10 g/dL, >/=50% decrease basal Plt or <100,000/mm^3 at >/=3 months post-treatment was PD if clonal CLL cell infiltration on BM biopsy. CR: no ADP/VSM in PE; no general Sx; blood Lymph <4000/mm^3; Neut >1500/mm^3; Plt >100,000/mm^3; Hb >11 g/dL (no transfusion); normocellular BM with <30% Lymph; BM aspirate/biopsy with no lymphoid nodule infiltration. PR: >50% decrease blood Lymph; >50% decrease in total sum up to 6 ADPs or baseline ADP of LD, no new/enlargement of prior ADP; >50% decrease VSM; Neut >1500/mm^3 or >50% increase; Plt >100,000/mm^3 or >50% increase; Hb >11.0 g/dL or >50% increase (no transfusion). All CR criteria but persistent anemia or thrombocytopenia was PR. MRD: Lymph >0.01% of blood/BM WBCs.
Measured: From first CR or PR up to detectable MRD or disease occurrence/PD, whichever occurred first (up to 92 months)
Percentage of Participants With Cluster of Differentiation (CD) 38 Cells >/=30% in Peripheral Blood
Percentages of participants with CD38 expression by >/=30% of CLL cells during the Induction Phase, Maintenance Phase, and Follow-Up were reported.
Measured: Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up: at Follow-Up Months 6, 12, 18, 24, 30, 36
Percentage of Participants With Genetic Abnormalities
Percentages of participants with genetic abnormalities (deletion 6q, deletion 11q22-q23, deletion p53, trisomy 12, and deletion 13q14) in the course of the disease during the Induction Phase and Maintenance Phase were reported.
Measured: Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months)
Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression
Percentages of participants with positive and negative ZAP-70 expression during the Induction Phase, Maintenance Phase, and Follow-Up were reported. Positive ZAP-70 was defined as ZAP-70 expression by >/=20% of CLL cells. Negative ZAP-70 was defined as ZAP-70 expression by <20% of CLL cells.
Measured: Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up: at Follow-Up Months 6, 12, 18, 24, 30, 36
Percentage of Participants With Immunoglobulin Heavy Locus (IgH) Rearrangement
Percentages of participants with IgH rearrangement during the Induction Phase, Maintenance Phase, and Follow-Up were reported.
Measured: Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up: at Follow-Up Months 6, 12, 18, 24, 30, 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2007 (estimated)
- Study start21 Nov 2007
- Primary completion20 May 2016
- Study completion20 May 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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Leukemia, Lymphocytic, Chronic, B-CellStudies 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
- 86 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
- NCT00545714
- Sponsor's protocol ID
- ML21135
- Other IDs
- 2007-002733-36
- Status last verified
- Jul 2018
- First submitted
- 16 Oct 2007
- Last updated
- 16 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Garcia-Marco JA, Jimenez JL, Recasens V, Zarzoso MF, Gonzalez-Barca E, De Marcos NS, Ramirez MJ, Parraga FJP, Yanez L, De La Serna Torroba J, Malo MDG, Ariznavarreta GD, Persona EP, Guinaldo MAR, De Paz Arias R, Llanos EB, Jarque I, Valle MDCF, Tatay AC, De Oteyza JP, Martin EMD, Fernandez IP, Martinez RM, Costa MAA, Champ D, Suarez JG, Diaz MG, Ferrer S, Carbonell F, Garcia-Vela JA; GELLC Study Group. High prognostic value of measurable residual disease detection by flow cytometry in chronic lymphocytic leukemia patients treated with front-line fludarabine, cyclophosphamide, and rituximab, followed by three years of rituximab maintenance. Haematologica. 2019 Nov;104(11):2249-2257. doi: 10.3324/haematol.2018.204891. Epub 2019 Mar 19.
PubMed 30890600
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicentre, Non-Randomised, Open-Label Phase II Study to Evaluate the Efficacy and Safety of Induction Treatment With Rituximab, Fludarabine, Cyclophosphamide, Followed by Rituximab Maintenance Therapy (R-Fc-Rm) in the First Line Treatment of Chronic Lymphocytic Leukaemia
- ClinicalTrials.gov ID
- NCT00545714
- Acronym / sponsor ID
- ML21135
- Conditions
- Leukemia, Lymphocytic, Chronic, B-Cell
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 21 Nov 2007 (actual)
- Primary completion
- 20 May 2016 (actual)
- Study completion
- 20 May 2016 (actual)
- First posted
- 17 Oct 2007 (estimated)
- Results
- Posted 16 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This single arm study will assess the efficacy and safety of rituximab in combination with fludarabine and cyclophosphamide, followed by rituximab maintenance therapy, as first line treatment of participants with 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 6 cycles (cycle length = 28 days) of treatment with rituximab (375 milligrams per square meter [mg/m^2] as intravenous [IV] infusion on Day 0 of Cycle 1 and 500 mg/m^2 as IV infusion on Day 1 of Cycles 2-6); fludarabine (25 mg/m^2 on Days 1-3) and cyclophosphamide (250 mg/m^2 on Days 1-3). Participants with a partial or complete response and appropriate neutrophil conditions will receive maintenance treatment with rituximab (375 mg/m^2 as IV infusion every 2 months) from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- CLL according to World Health Organization diagnostic criteria
- Active disease
- No previous treatment
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
Key exclusion criteria (4 listed)
- Transformation to aggressive B-cell malignancy (prolymphocytic leukemia, large-cell lymphoma, Hodgkin's lymphoma)
- Other malignancies except for localized skin cancer
- Continuous systemic corticosteroid treatment
- Known infection with hepatitis B or C
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 250 mg/m^2 as IV infusion will be administered on Days 1-3 of first six 28-day cycles. | Drug | Rituximab + Fludarabine + Cyclophosphamide |
| FludarabineFludarabine 25 mg/m^2 as IV infusion will be administered on Days 1-3 of first six 28-day cycles. | Drug | Rituximab + Fludarabine + Cyclophosphamide |
| RituximabAlso: MabThera, RituxanRituximab 375 mg/m^2 as IV infusion will be administered on Day 0 of Cycle 1; 500 mg/m^2 as IV infusion will be administered on Day 1 of Cycle 2-6; and 375 mg/m^2 as IV infusion every 2 months from 3 months after Day 1 Cycle 6 up to a total of 18 doses or up to 3 years after Cycle 6. | Drug | Rituximab + Fludarabine + Cyclophosphamide |
Primary outcome
Percentage of Participants With CR Achieved After the Rituximab, Fludarabine, and Cyclophosphamide Regimen
Time frame: Month 9
CR was defined as no adenopathies (ADPs) and visceromegalies (VSMs) in physical examination (PE); no general symptoms (Sx); lymphocytes (Lymph) in peripheral blood less than (<) 4000 per cubic millimeter (mm^3); normalization of peripheral blood parameters: neutrophils (Neut) greater than (>) 1500/mm^3, platelets (Plt) >100,000/mm^3, hemoglobin (Hb) >11 grams per deciliter (g/dL) without transfusion; normocellular bone marrow (BM) with <30% Lymph; BM aspirate/biopsy with no evidence of infiltration of lymphoid nodules.
13 secondary outcomes
Percentage of Participants With Clinical Response of CR or PR as Assessed by Multiparameter Flow Cytometry
Time frame: Post-Induction Phase (IP): at 6 months; during Maintenance Phase (MP): at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up (FU): at Follow-Up Months 6, 12, 18, 24, 30, 36
Percentage of Participants With Clinical Response of CR or PR Among Participants With Negative Minimal Residual Disease (MRD) as Assessed by Multiparameter Flow Cytometry
Time frame: Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up: at Follow-Up Months 6, 12, 18, 24, 36
Percentage of Participants With CR With Incomplete Bone Marrow Recovery (CRi)
Time frame: Baseline up to progressive disease (PD) or death due to any cause, whichever occurred first (up to 92 months)
Percentage of Participants Who Died
Time frame: Baseline up to death due to any cause (up to 92 months)
Overall Survival (OS)
Time frame: Baseline up to death due to any cause (up to 92 months)
Percentage of Participants With PD or Death
Time frame: Baseline up to PD or death due to any cause, whichever occurred first (up to 92 months)
Progression-Free Survival (PFS)
Time frame: Baseline up to PD or death due to any cause, whichever occurred first (up to 92 months)
Treatment-Free Survival (TFS)
Time frame: Baseline up to PD or death due to any cause, whichever occurred first (up to 92 months)
Duration of Response (DOR)
Time frame: From first CR or PR up to detectable MRD or disease occurrence/PD, whichever occurred first (up to 92 months)
Percentage of Participants With Cluster of Differentiation (CD) 38 Cells >/=30% in Peripheral Blood
Time frame: Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up: at Follow-Up Months 6, 12, 18, 24, 30, 36
Percentage of Participants With Genetic Abnormalities
Time frame: Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months)
Percentage of Participants With Positive and Negative Zeta-Chain-Associated Protein Kinase 70 (ZAP-70) Expression
Time frame: Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up: at Follow-Up Months 6, 12, 18, 24, 30, 36
Percentage of Participants With Immunoglobulin Heavy Locus (IgH) Rearrangement
Time frame: Post-Induction Phase: at 6 months; during Maintenance Phase: at Cycles 9, 12, 15, 18 (cycle length = 2 months); during Follow-Up: at Follow-Up Months 6, 12, 18, 24, 30, 36
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30890600Garcia-Marco JA, Jimenez JL, Recasens V, Zarzoso MF, Gonzalez-Barca E, De Marcos NS, Ramirez MJ, Parraga FJP, Yanez L, De La Serna Torroba J, Malo MDG, Ariznavarreta GD, Persona EP, Guinaldo MAR, De Paz Arias R, Llanos EB, Jarque I, Valle MDCF, Tatay AC, De Oteyza JP, Martin EMD, Fernandez IP, Martinez RM, Costa MAA, Champ D, Suarez JG, Diaz MG, Ferrer S, Carbonell F, Garcia-Vela JA; GELLC Study Group. High prognostic value of measurable residual disease detection by flow cytometry in chronic lymphocytic leukemia patients treated with front-line fludarabine, cyclophosphamide, and rituximab, followed by three years of rituximab maintenance. Haematologica. 2019 Nov;104(11):2249-2257. doi: 10.3324/haematol.2018.204891. Epub 2019 Mar 19.
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RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
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
33 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 Cyclophosphamide, Fludarabine and Rituximab in people with Leukemia, Lymphocytic, Chronic, B-Cell, run by Hoffmann-La Roche at 33 sites in Spain.
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 4 inclusion and 4 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 16 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 33 sites in Spain. 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 16 Jan 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 CR Achieved After the Rituximab, Fludarabine, and Cyclophosphamide Regimen (time frame: Month 9). 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 NCT00545714, which also lists 1 linked publication.
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 16 Jan 2019.