LeukemiaPhase 2NCT00337246
Combination Chemotherapy With or Without Rituximab in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia
A Phase 2 study testing rituximab, cyclophosphamide and fludarabine phosphate in people with Leukemia, run by Cancer Research UK at 16 sites in United Kingdom.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as fludarabine, cyclophosphamide, and mitoxantrone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Leukemia
- What is being tested?
- rituximab, cyclophosphamide and fludarabine phosphate
- How many people
- 56 participants
- Where
- 16 sitesUnited Kingdom
- Study dates
- Jul 2005to Mar 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
DISEASE CHARACTERISTICS:
- Diagnosis of chronic lymphocytic leukemia requiring therapy
- Previously treated with ≥ 1 chemotherapeutic regimen
PATIENT CHARACTERISTICS:
- WHO performance status 0-2
- Life expectancy ≥ 12 weeks
- Creatinine clearance ≥ 30 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile female patients must use effective contraception for 4 weeks before, during, and for 6 months after completion of study treatment
- Fertile male patients must use effective contraception during and for 6 months after completion of study treatment
- No history of anaphylaxis after exposure to rat or mouse-derived complementary-determining region (CDR)-grafted humanized monoclonal antibodies
- No toxicity attributable to purine analogues (e.g., autoimmune hemolytic anemia, neurological toxicity, or allergy)
- No active infection
- No other severe (particularly cardiac or pulmonary) diseases or mental disorders that would preclude study participation
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior fludarabine (or other purine analogues) combined with cyclophosphamide and mitoxantrone hydrochloride
- No prior rituximab, either alone or in combination with chemotherapy
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United Kingdom16 sites
Monklands General Hospital
Airdrie, Scotland, ML6 0JF
Birmingham Heartlands Hospital
Birmingham, England, B9 5SS
Blackpool Victoria Hospital
Blackpool, England, FY3 8NR
Kent and Canterbury Hospital
Canterbury, England, CT2 7NR
University Hospital of Wales
Cardiff, Wales, CF14 4XW
St Helier Hospital
Carshalton, England, SM5 1AA
Darent Valley Hospital
Dartford Kent, England, DA2 8DA
Medway Maritime Hospital
Gillingham Kent, England, ME7 5NY
Leeds General Infirmary at Leeds Teaching Hospital NHS Trust
Leeds, England, LS1 3EX
Leicester Royal Infirmary
Leicester, England, LE1 5WW
Royal Liverpool and Broadgreen Hospitals NHS Trust
Liverpool, England, L7 8XP
Maidstone Hospital
Maidstone, England, ME16 9QQ
Christie Hospital NHS Trust
Manchester, England, M20 4BX
Royal Cornwall Hospital
Truro, Cornwall, England, TR1 3LJ
Kent and Sussex Hospital
Tunbridge Wells, Kent, England, TN4 8AT
Wishaw General Hospital
Wishaw, England, ML2 0DP
About this study
Official title: A Randomized Phase II Trial of Fludarabine, Cyclophosphamide and Mitoxantrone (FCM) With or Without Rituximab in Previously Treated Chronic Lymphocytic Leukemia
RATIONALE: Drugs used in chemotherapy, such as fludarabine, cyclophosphamide, and mitoxantrone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving combination chemotherapy together with rituximab may kill more cancer cells. It is not yet known whether giving combination chemotherapy together with rituximab is more effective than combination chemotherapy alone in treating chronic lymphocytic leukemia.
PURPOSE: This randomized phase II trial is studying how well giving combination chemotherapy with or without rituximab works in treating patients with previously treated chronic lymphocytic leukemia.
Read the detailed description
OBJECTIVES:
Primary
- Assess the efficacy and safety of fludarabine, cyclophosphamide, and mitoxantrone hydrochloride with or without rituximab in patients with previously treated chronic lymphocytic leukemia.
- Determine the overall response rate, defined as complete or partial remission, in these patients.
Secondary
- Determine the proportion of patients with undetectable minimal residual disease.
- Determine the 2-year progression-free survival of these patients.
- Determine the 2-year overall survival of these patients.
- Determine the toxicity of this regimen.
OUTLINE: This is a randomized, controlled, open-label, parallel group, multicenter study. Patients are stratified according to prior treatment with fludarabine (refractory vs not refractory or naive). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral fludarabine* and oral cyclophosphamide* on days 1-5 and mitoxantrone hydrochloride IV on day 1.
- Arm II: Patients receive fludarabine*, cyclophosphamide*, and mitoxantrone hydrochloride as in arm I. Patients also receive rituximab IV on day 1.
NOTE: *If the oral regimen is not tolerated, patients may receive fludarabine IV and cyclophosphamide IV on days 1-3.
Treatment in both arms repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for 3 years.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
PROJECTED ACCRUAL: A total of 56 patients will be accrued for this study.
- Conditions
- Leukemia
- Being tested
- rituximab, cyclophosphamide, fludarabine phosphate, mitoxantrone hydrochloride
- Keywords
- refractory chronic lymphocytic leukemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia
- Medical subject headings
- Leukemia, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rituximabBiological
cyclophosphamideDrug
mitoxantrone hydrochlorideDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate as measured by NCI Response Criteria
Secondary outcomes (4)
Proportion of patients with undetectable minimal residual disease
Progression-free survival at 2 years
Overall survival at 2 years
Toxicity
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2006 (estimated)
- Study startJul 2005
- Study completionMar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cancer Research UK
- Sponsor type
- University, hospital or other
- Investigators
- Peter Hillmen, MD, Study chair, Leeds General Infirmary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00337246
- Sponsor's protocol ID
- CTRU-NCRI-UKCLL01-FCM/FCM-R
- Other IDs
- CDR0000485181, EU-20626, ROCHE-NCRI-UKCLL01-FCM/FCM-R, ISRCTN77546448, EUDRACT-2004-003982-34
- Status last verified
- May 2007
- First submitted
- 13 Jun 2006
- Last updated
- 2 Aug 2013
- Results posted
- No
Publications
Hillmen P, Cohen DR, Cocks K, Pettitt A, Sayala HA, Rawstron AC, Kennedy DB, Fegan C, Milligan DW, Radford J, Mercieca J, Dearden C, Ezekwisili R, Smith AF, Brown J, Booth GA, Varghese AM, Pocock C; NCRI CLL Sub-Group. A randomized phase II trial of fludarabine, cyclophosphamide and mitoxantrone (FCM) with or without rituximab in previously treated chronic lymphocytic leukaemia. Br J Haematol. 2011 Mar;152(5):570-8. doi: 10.1111/j.1365-2141.2010.08317.x. Epub 2011 Jan 14.
PubMed 21231927
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II Trial of Fludarabine, Cyclophosphamide and Mitoxantrone (FCM) With or Without Rituximab in Previously Treated Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT00337246
- Acronym / sponsor ID
- CTRU-NCRI-UKCLL01-FCM/FCM-R
- Conditions
- Leukemia
- Keywords
- refractory chronic lymphocytic leukemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (estimated)
- Lead sponsor
- Cancer Research UKUniversity, hospital or other
- Study start
- Jul 2005
- Study completion
- Mar 2011 (actual)
- First posted
- 15 Jun 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy, such as fludarabine, cyclophosphamide, and mitoxantrone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving combination chemotherapy together with rituximab may kill more cancer cells. It is not yet known whether giving combination chemotherapy together with rituximab is more effective than combination chemotherapy alone in treating chronic lymphocytic leukemia.
PURPOSE: This randomized phase II trial is studying how well giving combination chemotherapy with or without rituximab works in treating patients with previously treated chronic lymphocytic leukemia.
Detailed description
OBJECTIVES:
Primary
- Assess the efficacy and safety of fludarabine, cyclophosphamide, and mitoxantrone hydrochloride with or without rituximab in patients with previously treated chronic lymphocytic leukemia.
- Determine the overall response rate, defined as complete or partial remission, in these patients.
Secondary
- Determine the proportion of patients with undetectable minimal residual disease.
- Determine the 2-year progression-free survival of these patients.
- Determine the 2-year overall survival of these patients.
- Determine the toxicity of this regimen.
OUTLINE: This is a randomized, controlled, open-label, parallel group, multicenter study. Patients are stratified according to prior treatment with fludarabine (refractory vs not refractory or naive). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral fludarabine* and oral cyclophosphamide* on days 1-5 and mitoxantrone hydrochloride IV on day 1.
- Arm II: Patients receive fludarabine*, cyclophosphamide*, and mitoxantrone hydrochloride as in arm I. Patients also receive rituximab IV on day 1.
NOTE: *If the oral regimen is not tolerated, patients may receive fludarabine IV and cyclophosphamide IV on days 1-3.
Treatment in both arms repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for 3 years.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
PROJECTED ACCRUAL: A total of 56 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rituximab | Biological | – |
| cyclophosphamide | Drug | – |
| fludarabine phosphate | Drug | – |
| mitoxantrone hydrochloride | Drug | – |
Primary outcome
Overall response rate as measured by NCI Response Criteria
4 secondary outcomes
Proportion of patients with undetectable minimal residual disease
Progression-free survival at 2 years
Overall survival at 2 years
Toxicity
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2013.
- Results publication: PubMed 21231927Hillmen P, Cohen DR, Cocks K, Pettitt A, Sayala HA, Rawstron AC, Kennedy DB, Fegan C, Milligan DW, Radford J, Mercieca J, Dearden C, Ezekwisili R, Smith AF, Brown J, Booth GA, Varghese AM, Pocock C; NCRI CLL Sub-Group. A randomized phase II trial of fludarabine, cyclophosphamide and mitoxantrone (FCM) with or without rituximab in previously treated chronic lymphocytic leukaemia. Br J Haematol. 2011 Mar;152(5):570-8. doi: 10.1111/j.1365-2141.2010.08317.x. Epub 2011 Jan 14.
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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.
Peter Hillmen, MD study chair
Leeds General Infirmary
16 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 rituximab, cyclophosphamide and fludarabine phosphate in people with Leukemia, run by Cancer Research UK at 16 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United Kingdom. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Overall response rate as measured by NCI Response Criteria. 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 NCT00337246, 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 2 Aug 2013.