Waldenström MacroglobulinemiaPhase 3NCT00566332
Trial Comparing Chlorambucil to Fludarabine in Patients With Advanced Waldenström Macroglobulinemia
A Phase 3 study testing Chlorambucil and Fludarabine in people with Waldenström Macroglobulinemia and Lymphoplasmacytic Lymphoma, run by French Study Group on Chronic Lymphoid Leukemia at 1 site in France.
Trial summary
Waldenström's macroglobulinaemia (WM) is a lymphoproliferative disorder characterized by a monoclonal IgM paraprotein and morphological evidence of lymphoplasmacytic lymphoma: the cells are IgM+, IgD+, CD19+ and CD20+ but usually CD5-, CD10- and CD23-. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Waldenström Macroglobulinemia, Lymphoplasmacytic Lymphoma, Splenic Marginal Zone Lymphoma
- What is being tested?
- Chlorambucil and Fludarabine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 414 participants
- Where
- 1 siteFrance
- Study dates
- Jun 2001to Dec 2014
- Phase
- Phase 3
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Established diagnosis of Waldenström macroglobulinemia (the 2nd Workshop on Waldenstrom's macroglobulinemia) or Lymphoplasmacytic lymphoma or Splenic Marginal Zone Lymphoma, needing a treatment
- Life expectancy > 6 months
- Creatinine < 200 µmol/l
- SGPT and SGOT < 2x ULN
- A negative direct Coombs test
- Written informed consent
Who cannot join
- Past chemotherapy/radiotherapy/immunotherapy prior to the study for Waldenström macroglobulinemia
- Previous malignancy less than 5 years ago except carcinoma in situ of the cervix and non-melanoma skin cancer
- Positive HIV serology
- Active Hepatitis B or C
- Lactation/pregnancy
- Impossible good compliance with the study protocol
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- Active infection not controlled
- Psychological condition hampering understanding of the study
- Transformation into large B cell lymphoma
- Peripheral neuropathy > grade II
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Trial Comparing the Efficacy of Chlorambucil to Fludarabine in Patients With Advanced Waldenström Macroglobulinemia,Lymphoplasmacytic Lymphoma or Splenic Marginal Zone Lymphoma
Waldenström's macroglobulinaemia (WM) is a lymphoproliferative disorder characterized by a monoclonal IgM paraprotein and morphological evidence of lymphoplasmacytic lymphoma: the cells are IgM+, IgD+, CD19+ and CD20+ but usually CD5-, CD10- and CD23-. The treatment efficacy is difficult to assess because of the lack of clear diagnostic criteria , good response criteria, and of randomized trials.
The actual treatment is Chlorambucil, an alkylating agent. A purine analogue such as Fludarabine has proven its efficacy on 30 % to 80 % as first line therapy
Read more
This study is a phase II b open, prospective, international multicenter trial (England, Dr Johnson, Dr Catovsky, Australia: Dr Seymour) promoted by the French Cooperative Group on Chronic Lymphoid Leukemia in untreated WM, or closely related disorders ( Lymphoplasmacytic lymphoma or splenic marginal zone lymphoma). 366 patients must be included, among them 180 patients in France. Patients will be stratified according to the lymphoproliferative disorder.
The patients will receive Chlorambucil by oral route for 10 days every 28 days (12 cycles) (8 MG/M², 6 MG/M² if patient is more than 75 years old) or Fludarabine by oral route for 5 days every 28 days (6 cycles) (40MG/M², 30 MG/M² if patient is more than 75 years old).
The primary objective is to compare the efficacy (response rate) of Chlorambucil to Fludarabine in previously untreated patients. The secondary objectives are the duration of response, the improvement of hematological parameters, the toxicity, the quality of life, the event free survival and the overall survival.
- Being tested
- Chlorambucil, Fludarabine
- Keywords
- Waldenström Macroglobulinemia, Lymphoplasmacytic lymphoma, Splenic Marginal Zone Lymphoma, Fludarabine, Chlorambucil
- Medical subject headings
- Waldenstrom Macroglobulinemia, Lymphoma, B-Cell, Marginal Zone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChlorambucilDrug
Chlorambucil 8 mg/m² (6 mg/m² if patient aged more than 75 years old) 10 days every 28 days during 12 months By oral route
FludarabineDrug
Fludarabine 40 mg/m² (30 mg/m² if patient aged more than 75 years old) 5 days every 28 days during 6 cycles By oral route
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Chlorambucil 8mg/m² (6 mg/m² if patient aged more than 75 years old) 10 days every 28 days during 12 months Receives: Drug: Chlorambucil |
| 2 | Active comparator | Fludarabine Receives: Drug: Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Patient overall response
Measured: At the end of treatment whether 6 or 12 months
Secondary outcomes (6)
Biological study
Measured: Whether 6 or 12 months
Quality of life
Measured: Whether 6 or 12 months
Response duration
Measured: 60 months
Treatment toxicity
Measured: 60 months
Event free survival
Measured: 60 months
Overall survival
Measured: 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2007 (estimated)
- Study startJun 2001
- Primary completionSep 2009
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Waldenström MacroglobulinemiaStudies 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
- 414 participants (actual)
Sponsor and investigators
- Lead sponsor
- French Study Group on Chronic Lymphoid Leukemia
- Sponsor type
- Research network
- Collaborators
- Lymphoma Study Association, French Innovative Leukemia Organisation, Département de Biostatistiques et Informatique Médicale DBIM
- Responsible party
- Sponsor
- Investigators
- Véronique LEBLOND, Professor, Principal investigator, French Study Group on Chronic Lymphoid Leukemia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00566332
- Sponsor's protocol ID
- WM1
- Status last verified
- Aug 2015
- First submitted
- 30 Nov 2007
- Last updated
- 19 Aug 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Leblond V, Johnson S, Chevret S, Copplestone A, Rule S, Tournilhac O, Seymour JF, Patmore RD, Wright D, Morel P, Dilhuydy MS, Willoughby S, Dartigeas C, Malphettes M, Royer B, Ewings M, Pratt G, Lejeune J, Nguyen-Khac F, Choquet S, Owen RG. Results of a randomized trial of chlorambucil versus fludarabine for patients with untreated Waldenstrom macroglobulinemia, marginal zone lymphoma, or lymphoplasmacytic lymphoma. J Clin Oncol. 2013 Jan 20;31(3):301-7. doi: 10.1200/JCO.2012.44.7920. Epub 2012 Dec 10.
PubMed 23233721Nguyen-Khac F, Lambert J, Chapiro E, Grelier A, Mould S, Barin C, Daudignon A, Gachard N, Struski S, Henry C, Penther D, Mossafa H, Andrieux J, Eclache V, Bilhou-Nabera C, Luquet I, Terre C, Baranger L, Mugneret F, Chiesa J, Mozziconacci MJ, Callet-Bauchu E, Veronese L, Blons H, Owen R, Lejeune J, Chevret S, Merle-Beral H, Leblondon V; Groupe Francais d'Etude de la Leucemie Lymphoide Chronique et Maladie de Waldenstrom (GFCLL/MW); Groupe Ouest-Est d'etude des Leucemie Aigues et Autres Maladies du Sang (GOELAMS); Groupe d'Etude des Lymphomes de l'Adulte (GELA). Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenstrom's macroglobulinemia. Haematologica. 2013 Apr;98(4):649-54. doi: 10.3324/haematol.2012.070458. Epub 2012 Oct 12.
PubMed 23065509
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial Comparing the Efficacy of Chlorambucil to Fludarabine in Patients With Advanced Waldenström Macroglobulinemia,Lymphoplasmacytic Lymphoma or Splenic Marginal Zone Lymphoma
- ClinicalTrials.gov ID
- NCT00566332
- Acronym / sponsor ID
- WM1
- Keywords
- Waldenström Macroglobulinemia, Lymphoplasmacytic lymphoma, Splenic Marginal Zone Lymphoma, Fludarabine, Chlorambucil
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 414 participants (actual)
- Lead sponsor
- French Study Group on Chronic Lymphoid LeukemiaResearch network
- Collaborators
- Lymphoma Study Association, French Innovative Leukemia Organisation, Département de Biostatistiques et Informatique Médicale DBIM
- Study start
- Jun 2001
- Primary completion
- Sep 2009 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 3 Dec 2007 (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.
Waldenström's macroglobulinaemia (WM) is a lymphoproliferative disorder characterized by a monoclonal IgM paraprotein and morphological evidence of lymphoplasmacytic lymphoma: the cells are IgM+, IgD+, CD19+ and CD20+ but usually CD5-, CD10- and CD23-. The treatment efficacy is difficult to assess because of the lack of clear diagnostic criteria , good response criteria, and of randomized trials.
The actual treatment is Chlorambucil, an alkylating agent. A purine analogue such as Fludarabine has proven its efficacy on 30 % to 80 % as first line therapy
This study is a phase II b open, prospective, international multicenter trial (England, Dr Johnson, Dr Catovsky, Australia: Dr Seymour) promoted by the French Cooperative Group on Chronic Lymphoid Leukemia in untreated WM, or closely related disorders ( Lymphoplasmacytic lymphoma or splenic marginal zone lymphoma). 366 patients must be included, among them 180 patients in France. Patients will be stratified according to the lymphoproliferative disorder.
The patients will receive Chlorambucil by oral route for 10 days every 28 days (12 cycles) (8 MG/M², 6 MG/M² if patient is more than 75 years old) or Fludarabine by oral route for 5 days every 28 days (6 cycles) (40MG/M², 30 MG/M² if patient is more than 75 years old).
The primary objective is to compare the efficacy (response rate) of Chlorambucil to Fludarabine in previously untreated patients. The secondary objectives are the duration of response, the improvement of hematological parameters, the toxicity, the quality of life, the event free survival and the overall survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: ChlorambucilChlorambucil 8mg/m² (6 mg/m² if patient aged more than 75 years old) 10 days every 28 days during 12 months |
| 2 | Active comparator | Drug: FludarabineFludarabine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Established diagnosis of Waldenström macroglobulinemia (the 2nd Workshop on Waldenstrom's macroglobulinemia) or Lymphoplasmacytic lymphoma or Splenic Marginal Zone Lymphoma, needing a treatment
- Life expectancy > 6 months
- Creatinine < 200 µmol/l
- SGPT and SGOT < 2x ULN
- A negative direct Coombs test
Key exclusion criteria (10 listed)
- Past chemotherapy/radiotherapy/immunotherapy prior to the study for Waldenström macroglobulinemia
- Previous malignancy less than 5 years ago except carcinoma in situ of the cervix and non-melanoma skin cancer
- Positive HIV serology
- Active Hepatitis B or C
- Lactation/pregnancy
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 |
|---|---|---|
| ChlorambucilChlorambucil 8 mg/m² (6 mg/m² if patient aged more than 75 years old) 10 days every 28 days during 12 months By oral route | Drug | 1 |
| FludarabineFludarabine 40 mg/m² (30 mg/m² if patient aged more than 75 years old) 5 days every 28 days during 6 cycles By oral route | Drug | 2 |
Primary outcome
Patient overall response
Time frame: At the end of treatment whether 6 or 12 months
6 secondary outcomes
Biological study
Time frame: Whether 6 or 12 months
Quality of life
Time frame: Whether 6 or 12 months
Response duration
Time frame: 60 months
Treatment toxicity
Time frame: 60 months
Event free survival
Time frame: 60 months
Overall survival
Time frame: 60 months
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 19 Aug 2015.
- Derived from this study: PubMed 23233721Leblond V, Johnson S, Chevret S, Copplestone A, Rule S, Tournilhac O, Seymour JF, Patmore RD, Wright D, Morel P, Dilhuydy MS, Willoughby S, Dartigeas C, Malphettes M, Royer B, Ewings M, Pratt G, Lejeune J, Nguyen-Khac F, Choquet S, Owen RG. Results of a randomized trial of chlorambucil versus fludarabine for patients with untreated Waldenstrom macroglobulinemia, marginal zone lymphoma, or lymphoplasmacytic lymphoma. J Clin Oncol. 2013 Jan 20;31(3):301-7. doi: 10.1200/JCO.2012.44.7920. Epub 2012 Dec 10.
- Derived from this study: PubMed 23065509Nguyen-Khac F, Lambert J, Chapiro E, Grelier A, Mould S, Barin C, Daudignon A, Gachard N, Struski S, Henry C, Penther D, Mossafa H, Andrieux J, Eclache V, Bilhou-Nabera C, Luquet I, Terre C, Baranger L, Mugneret F, Chiesa J, Mozziconacci MJ, Callet-Bauchu E, Veronese L, Blons H, Owen R, Lejeune J, Chevret S, Merle-Beral H, Leblondon V; Groupe Francais d'Etude de la Leucemie Lymphoide Chronique et Maladie de Waldenstrom (GFCLL/MW); Groupe Ouest-Est d'etude des Leucemie Aigues et Autres Maladies du Sang (GOELAMS); Groupe d'Etude des Lymphomes de l'Adulte (GELA). Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenstrom's macroglobulinemia. Haematologica. 2013 Apr;98(4):649-54. doi: 10.3324/haematol.2012.070458. Epub 2012 Oct 12.
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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.
Véronique LEBLOND, Professor principal investigator
French Study Group on Chronic Lymphoid Leukemia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Chlorambucil and Fludarabine in people with Waldenström Macroglobulinemia and Lymphoplasmacytic Lymphoma, run by French Study Group on Chronic Lymphoid Leukemia at 1 site in France.
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 6 inclusion and 10 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 19 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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?
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?
Patient overall response (time frame: At the end of treatment whether 6 or 12 months). 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 NCT00566332, which also lists 2 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 19 Aug 2015.