B-Cell Chronic Lymphocytic LeukemiaPhase 3NCT00086580
Fludarabine (Fludara®) Plus Alemtuzumab (CAMPATH®, MabCampath®) vs Fludarabine Alone in B-Cell Chronic Lymphocytic Leukemia (B-CLL) Patients
A Phase 3 study testing FluCAM [Fludara + Campath] and fludarabine phosphate in people with B-Cell Chronic Lymphocytic Leukemia, run by Genzyme, a Sanofi Company at 48 sites in 15 countries.
Trial summary
This is a Phase 3, prospective, multicenter, open-label, randomized, controlled study to evaluate and compare the efficacy and safety of fludarabine plus alemtuzumab versus fludarabine alone as second-line therapy for patients with relapsed or refractory B-cell chronic lymphocytic leukemia (B-CLL). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- B-Cell Chronic Lymphocytic Leukemia
- What is being tested?
- FluCAM [Fludara + Campath] and fludarabine phosphate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 335 participants
- Where
- 48 sitesin 15 countries
- Study dates
- Jul 2004to Jun 2010
- Phase
- Phase 3
- 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
- A diagnosis of B-cell chronic lymphocytic leukemia (B-CLL); according to the National Cancer Institute Working Group (NCI WG) criteria.
- Relapsed or refractory disease after 1 prior regimen except patients who were refractory to (i.e., progressed on) fludarabine or alemtuzumab therapy. Patients who previously responded (complete response or partial response) to fludarabine or alemtuzumab therapy, but who have relapsed at the time of study entry, may be eligible but response to fludarabine or alemtuzumab therapy must have lasted >12 months (i.e., >12 months from a documented response to a documented relapse).
- Binet stage A, stage B, or stage C or Rai Stage I through IV disease with evidence of progression as evidenced by the presence of one or more of the following:
- Evidence of progressive marrow failure as manifested by: 1) a decrease in hemoglobin to <11g/dL, or 2) a decrease in platelet count to <100 x 10^9/L within the previous 6 months, or 3) a decrease in absolute neutrophil count (ANC) to <1.0 X 10^9/L.
- Progressive splenomegaly to >2 cm below the left costal margin or other organomegaly.
- Progressive lymphadenopathy.
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- Progressive lymphocytosis with an increase of 50% over a 2-month period, or an anticipated doubling time of less than 6 months.
- World Health Organization (WHO) performance status (PS) of 0 or 1.
- Life expectancy >12 weeks.
- Anti-cancer therapy, major surgery, or irradiation was completed >3 weeks before randomization in this study. Patient must have recovered from the acute side effects incurred as a result of previous therapy.
- Serum creatinine less than or equal to 2.0 x institutional upper limits of normal (ULN) and calculated creatinine clearance (CrCl) greater than or equal to 30mL/min using the Cockroft and Gault formula.
- Adequate liver function as indicated by a total bilirubin, AST, and ALT less than or equal to 2 x the institutional ULN value, unless directly attributable to the patient's tumor.
- Female patients with childbearing potential must have a negative serum pregnancy test with 2 weeks of first dose of study drug(s). Male and female patients must agree to use an effective contraceptive method while on study treatment, if appropriate, and for a minimum of 6 months following study therapy.
- Signed, written informed consent.
Who cannot join
- Previously treated with >1 prior regimen for B-CLL.
- Previously treated with a fludarabine plus alemtuzumab (FluCAM) regimen for B-CLL.
- Positive Coombs test and actively hemolyzing.
- Absolute neutrophil count (ANC) <1.5 x 10^9/L or platelet count <75 x 10^9/L, unless due to bone marrow involvement.
- Medical condition requiring chronic use of pharmacologic doses of oral corticosteroids, i.e. anything other than replacement dose levels.
- History of anaphylaxis following exposure to monoclonal antibodies.
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- Use of investigational agents within 6 weeks prior to study randomization.
- Active infection or history of severe infection (grade 4) within 3 months prior to study randomization.
- Known to be human immunodeficiency virus (HIV) positive.
- Autoimmune thrombocytopenia.
- Active second malignancy.
- Known central nervous system (CNS) involvement with B-CLL.
- Other severe, concurrent diseases, including tuberculosis, mental disorders, serious cardiac functional capacity (Class III or IV as defined by the New York Heart Association Classification), severe diabetes, severe hypertension, pulmonary disease (chronic obstructive pulmonary disease [COPD] with hypoxemia), or major organ malfunction (liver, kidney) that could interfere with the patient's ability to participate in the study.
- Pregnant or nursing women.
- Patients that have progressed with more aggressive B-cell cancers such as Richter's syndrome.
- Active hepatitis or a history of prior viral hepatitis B or hepatitis C, or positive hepatitis B serologies without prior immunization.
Trial locations and contacts
48 sites in 15 countries.
48 sites in 15 countries
Ukraine9 sites
Cherkasskly Oncology Dispensary
Cherkasy, 79044
City Clinical Hospital #4, Regional Hematology Center
Dnipro, 49102
Donetsk State Medical University
Donetsk, 83045
Kharkov Regional Clinical Oncology Center, Department of Hematology
Kharkiv, 61070
Khmelnitskiy Regional Hospital, Hematology Department
Khmelnitskiy, 29000
Institute of Oncology AMS of Ukraine
Kiev, 03022
Institute of Hematology and Transfusiology AMS of Ukraine, City Clinical Hospital #9
Kiev, 04112
Scientific Centre for Radiation Medicine AMS of Ukraine, Dept of Hematology and Transplantology
Kyiv, 03115
Lviv National Medical University named Danilo Galytcky
Lviv, 79044
Bulgaria5 sites
University Multiprofile Hospital for Active Treatment Dr. Georgi Stranski
Pleven, 5800
UMHAT St. Georgi, Hematology Clinic
Plovdiv, 4000
Multiprofile Hospital for Active Treatment "Alexandrovska"
Sofia, 1431
National Center for Heamtology and Transfusiology
Sofia, 1756
Multiprofile Hospital for Active Treatment, St. Marina
Varna, 9010
Poland5 sites
Klinika Hematologii i Transplantacji Szpiku
Katowice, 40-027
Klinika Hematologii AM
Lodz, 93-513
Klinika Hematologii Pomorskiej Akademii Medycznej w Szczecinie
Szczecin, 71-252
Katedra i Klinika Hamatologii, Onkologii I Chorob Wewnetrznych AM
Warsaw, 02-097
Klinika Hematologii, Nowotworow Krwii 1 Transplantacji Szpiku
Wroclaw, 50-367
Sweden5 sites
University Hospital, Dept. of Hematology
Lund, 221 85
Orebro University Hospital, Dep. of Medicine
Örebro, 701 85
Universitetssjukhuset
Örebro, 701 85
Medicin kliniken/Hematologsektionen
Sundsvall, 851 86
Akademiska sjukhuset
Uppsala, 751 85
Germany4 sites
Charite-Universitatsmedizin Berlin Campus Benjamin-Franklin
Berlin, 12203
Charite Universitatsklinikum der Humboldt-Universitat zu Berlin
Berlin, 13353
Klinikum der Universitat zu Koln, Klinik 1 fur Innere Medizin
Cologne, 50924
Robert-Bosch Krankenhaus GmbH
Stuttgart, 70376
Russia4 sites
GU "Main Military Clinical Hospital named after acad. N.N.Burdenko of MO of Russia", Haematology Centre 3
Moscow, 105229
GOUVPO "Saint-Petersburg State Medical University named after acad I.P.Pavlov of Roszdrav", Bone Marrow Transplantology Clinic
Saint Petersburg, 197089
Saint-Petersburg GUZ "City Hospital #31" 3, Dynamo Prospect
Saint Petersburg, 197110
State Healthcare Department "Sverdlovsk Regional Clinical Hospital #1",
Yekaterinburg, 620102
Croatia3 sites
Clinical Hospital Center Rijeka, Department of Haematology
Rijeka, 51000
Clinical Hospital Merkur
Zagreb, 10000
University Hospital Dubrava
Zagreb, 10000
Italy3 sites
U.O. Oncologia Medica Azienda Ospedaliera "Pugliese-Ciaccio"
Cantanzaro, 88100
Unita Operativa di Medicina Generale Reumatologia e Oncoematologia
Milan, 20132
Istituto di Ematologia Dipartmento di Biotechnologie Celluari ed Ematologia, Universita di Roma "La Sapienza"
Rome, 00161
Austria2 sites
Medizinische Universitatsklinik Graz
Graz, 8036
Universitat Wien AKH, Innere Medizin I
Vienna, 1090
Canada2 sites
Hopital Notre-Dame du CHUM
Montreal, Quebec, H2L 4M1
Cancer Care Manitoba
Winnipeg, Manitoba, R3E 0V9
Portugal2 sites
Hospital de Santa Maria Servico de Hematologia Clinica/Hospital de dia de Hematologia
Lisbon, 1649-035
Hospital de Sao Teotonio, Servico de Hematologia/Hosptial de Dia Oncologico
Viseu, 3504-509
United States1 site
Florida Cancer Specialists
Fort Myers, Florida, 33916
Greece1 site
"Laikon" General Hospital, University of Athens
Goudi, Athens, 11527
Romania1 site
Institutol Clinic Fundeni, Clinica Heamtologie
Bucharest, 022328
About this study
Official title: A Phase III Randomized Trial to Evaluate the Efficacy and Safety of Second-Line Therapy With Fludarabine Plus Alemtuzumab vs. Fludarabine Alone in Patients With B-Cell Chronic Lymphocytic Leukemia
This is a Phase 3, prospective, multicenter, open-label, randomized, controlled study to evaluate and compare the efficacy and safety of fludarabine plus alemtuzumab versus fludarabine alone as second-line therapy for patients with relapsed or refractory B-cell chronic lymphocytic leukemia (B-CLL). Patients who meet all eligibility criteria and sign the informed consent document may be entered on the study.
- Conditions
- B-Cell Chronic Lymphocytic Leukemia
- Being tested
- FluCAM [Fludara + Campath], fludarabine phosphate
- 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.
FluCAM [Fludara + Campath]Biological
Also called alemtuzumab, fludarabine phosphate, Fludara, Campath
Phase A: Escalating Doses of alemtuzumab (Campath) Alone
Day 1: alemtuzumab 3 mg intravenously (IV) over 2 hours.
Day 2: alemtuzumab 10 mg IV over 2 hours if 3 mg was tolerated, else repeat 3 mg daily until tolerated.
Day 3: alemtuzumab 30 mg IV over 2 hours if 10 mg was tolerated, else repeat 10 mg daily until tolerated.
Participants were allowed 3-14 days to escalate to 30 mg. Once 30 mg was tolerated, the participant had to begin Phase B within 7 days.
Phase B: FluCAM
Cycle 1: Days 1,2,3 fludarabine phosphate administered at 30 mg/m^2 over 30 minutes IV, followed within 1 hour by alemtuzumab 30 mg IV over 2 hours. A similar schedule is set for Cycles 2 through 6; duration of alemtuzumab infusions vary from 2-6 hours. Each 28-day period is 1 cycle. Fludarabine phosphate dosage is based on participants' body surface area at the beginning of each cycle. FluCAM administered up to a maximum of 6 cycles, based upon participants' response to therapy and toxicity.
fludarabine phosphateBiological
Also called Fludara
Fludarabine phosphate (Fludara) is administered at a dose of 25 mg/m^2 IV over 15 to 30 minutes daily for 5 consecutive days (days 1 through 5) every 28 days (per package instructions). Each 28-day period is 1 cycle. The dose of fludarabine phosphate will be based on the participant's body surface area as calculated at the beginning of each cycle. Participants treated with fludarabine phosphate up to a maximum of 6 cycles, based upon their response to therapy and toxicity.
| Study group | Role | What they receive |
|---|---|---|
| Combination Arm (FluCAM) | Experimental | Not described Receives: Biological: FluCAM [Fludara + Campath] |
| Fludarabine Alone | Active comparator | Not described Receives: Biological: fludarabine phosphate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Kaplan-Meier Estimates for Progression-free Survival (PFS) Based on Independent Response Review Panel (IRRP) Assessment
Progression-free survival was defined as the number of days from the date of randomization to the date of first objective documentation of progressive disease (PD) as determined by the treatment-blinded IRRP, or death due to any cause. Results are expressed in months.
Measured: Up to 6 years
Secondary outcomes (15)
Participant Best Response to Treatment Assessed by the Independent Response Review Panel (IRRP)
Participants were evaluated by the IRRP according to National Cancer Institute (NCI) 1996 response criteria. The best response observed during the study is summarized. Response categories include Complete Response (CR) with normal physical exam, marrow cells and blood values, Partial Response (PR) with a >= 50% decrease from baseline in lymphocytes, lymphadenopathy and liver or spleen exam, Stable Disease (SD) without significant progression from baseline, or Progressive Disease (PD) with increased size/number of nodes, size of liver or spleen, increase in lymphocytes, aggressive histology.
Measured: Up to 9 months
Kaplan-Meier Estimates of Overall Survival Time
Overall survival was defined as the time in days from the date of randomization to the date of death due to any cause plus 1 day for all participants. Results are stated in months.
Measured: Up to 6 years
Kaplan Meier Estimates for Time to Disease Progression Assessed by the Independent Response Review Panel (IRRP)
Time to disease progression was defined as the number of days from the date of randomization to the date of first objective documentation of progressive disease as determined by IRRP. Results are stated in months.
Measured: Up to 6 years
Kaplan-Meier Estimates for Duration of Response Assessed by the Independent Response Review Panel (IRRP)
Duration of response was analyzed for participants who achieved a complete response (CR) or partial response (PR) and was defined as the number of days from the first date of documented response to the date of progressive disease as determined by IRRP or death due to any cause. Results are stated in months.
Measured: Up to 6 years
Kaplan-Meier Estimates for Time to Alternative Therapy
Time to alternative therapy was defined as the number of days from the date of randomization to the date of first alternative therapy for chronic lymphocytic leukemia (CLL) or death resulting from any cause. Participants who had not received alternative therapy as of the data cutoff date were censored at the last follow-up visit assessment date plus 1 day. Results are stated in months.
Measured: Up to 6 years
Mean EQ-5D™ Index Scores to Measure Quality of Life at Baseline
EQ-5D™ is a trademark of the EuroQol Group. EQ-5D™ is a standardized instrument for use as a measure of health outcome. The questionnaire asks about health status along 5 dimensions: mobility, self care, usual activities, pain/discomfort, and anxiety/depression, which are rated at three possible levels (no problems, some problems, extreme problems). The score ranges from best (+1) to worst (-0.59).
Measured: Day 0 (baseline)
Mean EQ-5D™ Index Scores to Measure Quality of Life at End of Treatment
EQ-5D™ is a trademark of the EuroQol Group. EQ-5D™ is a standardized instrument for use as a measure of health outcome. The questionnaire asks about health status along 5 dimensions: mobility, self care, usual activities, pain/discomfort, and anxiety/depression, which are rated at three possible levels (no problems, some problems, extreme problems). The score ranges from best (+1) to worst (-0.59).
Measured: up to month 6 (end of treatment)
Mean EuroQol Visual Analogue Scale (EQ-VAS) Scores to Measure Quality of Life at Baseline
The EuroQol Visual Analogue Scale (EQ-VAS) was also used to capture the self-rating of current health status using a visual "thermometer" with the end points of 100 (best imaginable health state) at the top and zero (worst imaginable health state) at the bottom.
Measured: Day 0 (baseline)
Mean EuroQol Visual Analogue Scale (EQ-VAS) Scores to Measure Quality of Life at End of Treatment
The EuroQol Visual Analogue Scale (EQ-VAS) was also used to capture the self-rating of current health status using a visual "thermometer" with the end points of 100 (best imaginable health state) at the top and zero (worst imaginable health state) at the bottom.
Measured: up to month 6 (end of treatment)
Summary of Participants With Adverse Experiences (AEs)
Number of participants with adverse events (AEs). AEs were graded by the investigator using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and were assessed for relatedness to study treatment (4 point scale from 'not related' to 'definitely related'). Categories reported include participant counts for treatment-emergent AEs, AEs for infections, serious AEs, AEs causing discontinuation of study drug(s), and deaths. Related AEs for the combination arm can be related to either fludarabine or alemtuzumab.
Measured: Up to 6 years
Mean Systemic Clearance (CL) of Fludarabine
Clearance of drug from plasma is affected by the absorption, distribution, metabolism and elimination of the drug. Mean systemic clearance of fludarabine is derived from plasma concentration versus time data.
Measured: month 4 (cycle 4): first day of dosing (pre-dose, 0.5 hr end of infusion), second day of dosing (pre-dose, 0.5 hr end of infusion), third day of dosing (pre-dose, 0.25 hr, 0.5 hr end of infusion, 1,2,3,4,6,24,48,72 hr after start of fludarabine infusion)
Total Volume of Distribution (Vss) of Fludarabine
The total volume of distribution (Vss) is the apparent volume in which fludarabine is distributed immediately after it has been injected intravenously and equilibrated between plasma and the surrounding tissues. Total volume of distribution (Vss) of fludarabine is derived from plasma concentration versus time data.
Measured: month 4 (cycle 4): first day of dosing (pre-dose, 0.5 hr end of infusion), second day of dosing (pre-dose, 0.5 hr end of infusion), third day of dosing (pre-dose, 0.25 hr, 0.5 hr end of infusion, 1,2,3,4,6,24,48,72 hr after start of fludarabine infusion)
Area Under the Curve (AUC) of Fludarabine From (AUC 0-tau)
AUC (0-tau) is the area under the plasma concentration curve for fludarabine over the dosage interval (tau).
Measured: month 4 (cycle 4): first day of dosing (pre-dose, 0.5 hr end of infusion), second day of dosing (pre-dose, 0.5 hr end of infusion), third day of dosing (pre-dose, 0.25 hr, 0.5 hr end of infusion, 1,2,3,4,6,24,48,72 hr after start of fludarabine infusion)
Maximum Plasma Concentration (Cmax) of Fludarabine
Cmax is the maximum plasma concentration of fludarabine observed.
Measured: month 4 (cycle 4): first day of dosing (pre-dose, 0.5 hr end of infusion), second day of dosing (pre-dose, 0.5 hr end of infusion), third day of dosing (pre-dose, 0.25 hr, 0.5 hr end of infusion, 1,2,3,4,6,24,48,72 hr after start of fludarabine infusion)
Participants With Minimal Residual Disease (MRD)
MRD negativity in this report was defined by the absence of tumor cells in bone marrow, using 4-color flow cytometry. MRD was assessed in participants with a clinical complete response (CR) or partial response (PR) without recovery of blood counts. MRD represents a very positive outcome.
Measured: up to 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2004 (estimated)
- Study startJul 2004
- Primary completionJun 2010
- Study completionJun 2010
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 (4)Papers the sponsor has linked to this study.
- Other trials for B-Cell Chronic Lymphocytic LeukemiaStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 335 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genzyme, a Sanofi Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Genzyme, a Sanofi Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00086580
- Sponsor's protocol ID
- CAM314
- Other IDs
- 2004-000149-39, 2004
- Status last verified
- Feb 2014
- First submitted
- 6 Jul 2004
- Last updated
- 13 Mar 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Engert A, et al. Overall Survival Advantage and Acceptable Safety Profile with Fludarabine in Combination with Alemtuzumab (FluCam) in Previously Treated Patients with Advanced Stage Chronic Lymphocytic Leukemia. Poster Presentation at American Society of Hematology 10 December 2010; Blood (ASH Annual Meeting Abstracts), Nov 2010;116:919. http://ash.confex.com/ash/2010/webprogram/Paper31687.html
Engert A, et al. Improved Progression-free Survival (PFS) of Alemtuzumab (Campath®, MabCampath®) plus Fludarabine (Fludara®) versus Fludarabine Alone as Second-line Treatment of Patients with B-Cell Chronic Lymphocytic Leukemia: Preliminary Results from a Phase III Randomized Trial. 51st ASH Annual Meeting. Blood 2009;114. Abstract 537. http://ash.confex.com/ash/2009/webprogram/Paper21929.html
Engert A, et al. Fludarabine (FLU) plus Alemtuzumab (FluCAM) Improves Progression Free Survival versus Fludarabine in Previously Treated Chronic Lymphocytic Leukemia and Demonstrates Activity in High Risk Patients. Poster Presentation at European Hematology Association 12 June 2010. Abstract 0768. http://www.eventure-online.com/eventure/publicAbstractView.do?id=136964&congressId=3446
Elter T, Gercheva-Kyuchukova L, Pylylpenko H, Robak T, Jaksic B, Rekhtman G, Kyrcz-Krzemien S, Vatutin M, Wu J, Sirard C, Hallek M, Engert A. Fludarabine plus alemtuzumab versus fludarabine alone in patients with previously treated chronic lymphocytic leukaemia: a randomised phase 3 trial. Lancet Oncol. 2011 Dec;12(13):1204-13. doi: 10.1016/S1470-2045(11)70242-X. Epub 2011 Oct 10.
PubMed 21992852
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Randomized Trial to Evaluate the Efficacy and Safety of Second-Line Therapy With Fludarabine Plus Alemtuzumab vs. Fludarabine Alone in Patients With B-Cell Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT00086580
- Acronym / sponsor ID
- CAM314
- Conditions
- B-Cell Chronic Lymphocytic Leukemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 335 participants (actual)
- Lead sponsor
- Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- Jul 2004
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 8 Jul 2004 (estimated)
- Results
- Posted 11 Aug 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 3, prospective, multicenter, open-label, randomized, controlled study to evaluate and compare the efficacy and safety of fludarabine plus alemtuzumab versus fludarabine alone as second-line therapy for patients with relapsed or refractory B-cell chronic lymphocytic leukemia (B-CLL). Patients who meet all eligibility criteria and sign the informed consent document may be entered on the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Combination Arm (FluCAM) | Experimental | Biological: FluCAM [Fludara + Campath] |
| Fludarabine Alone | Active comparator | Biological: fludarabine phosphate |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- A diagnosis of B-cell chronic lymphocytic leukemia (B-CLL); according to the National Cancer Institute Working Group (NCI WG) criteria.
- Relapsed or refractory disease after 1 prior regimen except patients who were refractory to (i.e., progressed on) fludarabine or alemtuzumab therapy. Patients who previously responded (complete response or partial response) to fludarabine or alemtuzumab therapy, but who have relapsed at the time of study entry, may be eligible but response to fludarabine or alemtuzumab therapy must have lasted >12 months (i.e., >12 months from a documented response to a documented relapse).
- Binet stage A, stage B, or stage C or Rai Stage I through IV disease with evidence of progression as evidenced by the presence of one or more of the following:
- Evidence of progressive marrow failure as manifested by: 1) a decrease in hemoglobin to <11g/dL, or 2) a decrease in platelet count to <100 x 10^9/L within the previous 6 months, or 3) a decrease in absolute neutrophil count (ANC) to <1.0 X 10^9/L.
- Progressive splenomegaly to >2 cm below the left costal margin or other organomegaly.
Key exclusion criteria (16 listed)
- Previously treated with >1 prior regimen for B-CLL.
- Previously treated with a fludarabine plus alemtuzumab (FluCAM) regimen for B-CLL.
- Positive Coombs test and actively hemolyzing.
- Absolute neutrophil count (ANC) <1.5 x 10^9/L or platelet count <75 x 10^9/L, unless due to bone marrow involvement.
- Medical condition requiring chronic use of pharmacologic doses of oral corticosteroids, i.e. anything other than replacement dose levels.
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 |
|---|---|---|
| FluCAM [Fludara + Campath]Also: alemtuzumab, fludarabine phosphate, Fludara, CampathPhase A: Escalating Doses of alemtuzumab (Campath) Alone Day 1: alemtuzumab 3 mg intravenously (IV) over 2 hours. Day 2: alemtuzumab 10 mg IV over 2 hours if 3 mg was tolerated, else repeat 3 mg daily until tolerated. Day 3: alemtuzumab 30 mg IV over 2 hours if 10 mg was tolerated, else repeat 10 mg daily until tolerated. Participants were allowed 3-14 days to escalate to 30 mg. Once 30 mg was tolerated, the participant had to begin Phase B within 7 days. Phase B: FluCAM Cycle 1: Days 1,2,3 fludarabine phosphate administered at 30 mg/m^2 over 30 minutes IV, followed within 1 hour by alemtuzumab 30 mg IV over 2 hours. A similar schedule is set for Cycles 2 through 6; duration of alemtuzumab infusions vary from 2-6 hours. Each 28-day period is 1 cycle. Fludarabine phosphate dosage is based on participants' body surface area at the beginning of each cycle. FluCAM administered up to a maximum of 6 cycles, based upon participants' response to therapy and toxicity. | Biological | Combination Arm (FluCAM) |
| fludarabine phosphateAlso: FludaraFludarabine phosphate (Fludara) is administered at a dose of 25 mg/m^2 IV over 15 to 30 minutes daily for 5 consecutive days (days 1 through 5) every 28 days (per package instructions). Each 28-day period is 1 cycle. The dose of fludarabine phosphate will be based on the participant's body surface area as calculated at the beginning of each cycle. Participants treated with fludarabine phosphate up to a maximum of 6 cycles, based upon their response to therapy and toxicity. | Biological | Fludarabine Alone |
Primary outcome
Kaplan-Meier Estimates for Progression-free Survival (PFS) Based on Independent Response Review Panel (IRRP) Assessment
Time frame: Up to 6 years
Progression-free survival was defined as the number of days from the date of randomization to the date of first objective documentation of progressive disease (PD) as determined by the treatment-blinded IRRP, or death due to any cause. Results are expressed in months.
15 secondary outcomes
Participant Best Response to Treatment Assessed by the Independent Response Review Panel (IRRP)
Time frame: Up to 9 months
Kaplan-Meier Estimates of Overall Survival Time
Time frame: Up to 6 years
Kaplan Meier Estimates for Time to Disease Progression Assessed by the Independent Response Review Panel (IRRP)
Time frame: Up to 6 years
Kaplan-Meier Estimates for Duration of Response Assessed by the Independent Response Review Panel (IRRP)
Time frame: Up to 6 years
Kaplan-Meier Estimates for Time to Alternative Therapy
Time frame: Up to 6 years
Mean EQ-5D™ Index Scores to Measure Quality of Life at Baseline
Time frame: Day 0 (baseline)
Mean EQ-5D™ Index Scores to Measure Quality of Life at End of Treatment
Time frame: up to month 6 (end of treatment)
Mean EuroQol Visual Analogue Scale (EQ-VAS) Scores to Measure Quality of Life at Baseline
Time frame: Day 0 (baseline)
Mean EuroQol Visual Analogue Scale (EQ-VAS) Scores to Measure Quality of Life at End of Treatment
Time frame: up to month 6 (end of treatment)
Summary of Participants With Adverse Experiences (AEs)
Time frame: Up to 6 years
Mean Systemic Clearance (CL) of Fludarabine
Time frame: month 4 (cycle 4): first day of dosing (pre-dose, 0.5 hr end of infusion), second day of dosing (pre-dose, 0.5 hr end of infusion), third day of dosing (pre-dose, 0.25 hr, 0.5 hr end of infusion, 1,2,3,4,6,24,48,72 hr after start of fludarabine infusion)
Total Volume of Distribution (Vss) of Fludarabine
Time frame: month 4 (cycle 4): first day of dosing (pre-dose, 0.5 hr end of infusion), second day of dosing (pre-dose, 0.5 hr end of infusion), third day of dosing (pre-dose, 0.25 hr, 0.5 hr end of infusion, 1,2,3,4,6,24,48,72 hr after start of fludarabine infusion)
Area Under the Curve (AUC) of Fludarabine From (AUC 0-tau)
Time frame: month 4 (cycle 4): first day of dosing (pre-dose, 0.5 hr end of infusion), second day of dosing (pre-dose, 0.5 hr end of infusion), third day of dosing (pre-dose, 0.25 hr, 0.5 hr end of infusion, 1,2,3,4,6,24,48,72 hr after start of fludarabine infusion)
Maximum Plasma Concentration (Cmax) of Fludarabine
Time frame: month 4 (cycle 4): first day of dosing (pre-dose, 0.5 hr end of infusion), second day of dosing (pre-dose, 0.5 hr end of infusion), third day of dosing (pre-dose, 0.25 hr, 0.5 hr end of infusion, 1,2,3,4,6,24,48,72 hr after start of fludarabine infusion)
Participants With Minimal Residual Disease (MRD)
Time frame: up to 9 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publicationEngert A, et al. Overall Survival Advantage and Acceptable Safety Profile with Fludarabine in Combination with Alemtuzumab (FluCam) in Previously Treated Patients with Advanced Stage Chronic Lymphocytic Leukemia. Poster Presentation at American Society of Hematology 10 December 2010; Blood (ASH Annual Meeting Abstracts), Nov 2010;116:919. http://ash.confex.com/ash/2010/webprogram/Paper31687.html
- Results publicationEngert A, et al. Improved Progression-free Survival (PFS) of Alemtuzumab (Campath®, MabCampath®) plus Fludarabine (Fludara®) versus Fludarabine Alone as Second-line Treatment of Patients with B-Cell Chronic Lymphocytic Leukemia: Preliminary Results from a Phase III Randomized Trial. 51st ASH Annual Meeting. Blood 2009;114. Abstract 537. http://ash.confex.com/ash/2009/webprogram/Paper21929.html
- Results publicationEngert A, et al. Fludarabine (FLU) plus Alemtuzumab (FluCAM) Improves Progression Free Survival versus Fludarabine in Previously Treated Chronic Lymphocytic Leukemia and Demonstrates Activity in High Risk Patients. Poster Presentation at European Hematology Association 12 June 2010. Abstract 0768. http://www.eventure-online.com/eventure/publicAbstractView.do?id=136964&congressId=3446
- Derived from this study: PubMed 21992852Elter T, Gercheva-Kyuchukova L, Pylylpenko H, Robak T, Jaksic B, Rekhtman G, Kyrcz-Krzemien S, Vatutin M, Wu J, Sirard C, Hallek M, Engert A. Fludarabine plus alemtuzumab versus fludarabine alone in patients with previously treated chronic lymphocytic leukaemia: a randomised phase 3 trial. Lancet Oncol. 2011 Dec;12(13):1204-13. doi: 10.1016/S1470-2045(11)70242-X. Epub 2011 Oct 10.
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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.
Medical Monitor study director
Genzyme, a Sanofi Company
48 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing FluCAM [Fludara + Campath] and fludarabine phosphate in people with B-Cell Chronic Lymphocytic Leukemia, run by Genzyme, a Sanofi Company at 48 sites in 15 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 14 inclusion and 16 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 13 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 48 sites in Ukraine, Bulgaria, Poland, Sweden, Germany and 10 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 11 Aug 2011). 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?
Kaplan-Meier Estimates for Progression-free Survival (PFS) Based on Independent Response Review Panel (IRRP) Assessment (time frame: Up to 6 years). 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 NCT00086580, which also lists 4 linked publications.
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 13 Mar 2014.