Waldenstrom's MacroglobulinaemiaPhase 2R2WNCT01592981
Randomised Trial in Waldenstrom's Macroglobulinaemia
A Phase 2 study testing Bortezomib, Cyclophosphamide and Rituximab in people with Waldenstrom's Macroglobulinaemia, run by University College, London at 30 sites in United Kingdom.
Trial summary
The purpose of this trial is to assess tolerability and efficacy of the Bortezomib, Cyclophosphamide and Rituximab combination as initial therapy for previously untreated patients with symptomatic Waldenstrom's macroglobulinaemia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Waldenstrom's Macroglobulinaemia
- What is being tested?
- Bortezomib, Cyclophosphamide and Rituximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 30 sitesUnited Kingdom
- Study dates
- Jan 2013to 2 Aug 2020
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Confirmed diagnosis of WM (according to consensus panel / WHO criteria) with measurable IgM paraprotein
- Previously untreated disease at any stage requiring therapy at the discretion of the treating physician. Suggested criteria for initiating treatment include:
- haematological suppression to Hb <10 g/dl, or neutrophils <1.5x109/l or platelets <150x109/l
- clinical evidence of hyperviscosity
- bulky lymphadenopathy and/or bulky splenomegaly
Show all 12Show fewer
- presence of B symptoms
- No previous chemotherapy (prior plasma exchange and steroids are permissible)
- Performance status grade 0 - 2
- Life expectancy of greater than 6 months
- Informed consent
- Agreed compliance with recommended contraceptive precautions where appropriate
Who cannot join
- Lymphoplasmacytic lymphoma with no detectable serum IgM paraprotein
- Severe pre-existing neuropathy (> grade 2)
- Autoimmune cytopenias
- Evidence of active Hepatitis B or C infection (patients with evidence of past HepB infection may be eligible - see appendix 6)
- Serological positivity for HIV
- Pregnant or lactating women
Show all 15Show fewer
- Life expectancy severely limited by other illness
- Renal failure (creatinine clearance <30 ml/min)
- Severe impairment of liver function: alkaline phosphatase/bilirubin >2.5 times upper limit of normal (ULN), ALT/AST >2.5 times ULN not related to lymphoma (patients with Gilbert syndrome are eligible)
- History of allergic reaction to compounds containing boron or mannitol
- Known hypersensitivity to murine compounds.
- Diagnosed or treated for a malignancy other than WM within 5 years before day 1 of Cycle 1 with the exception of complete resection of basal cell carcinoma, squamous cell carcinoma of the skin or any other in situ malignancy
- Active systemic infection requiring treatment
- Concurrent treatment with another investigational agent
- Severe or life-threatening cardiac, pulmonary, neurological, psychiatric or metabolic disease
Trial locations and contacts
30 sites in 1 country.
30 sites in 1 country
United Kingdom30 sites
Basingstoke & North Hampshire Hospital
Basingstoke
Royal United Hospital
Bath
Birmingham Heartlands Hospital
Birmingham, B9 5SS
City Hospital
Birmingham
Pilgrim Hospital
Boston
Colchester General Hospital
Colchester
Darent Valley Hospital
Dartford
Dewsbury and District Hospital
Dewsbury
Royal Devon and Exeter Hospital
Exeter
Grantham and District Hospital
Grantham
St James University Hospital
Leeds, LS9 7TF
Leicester Royal Infirmary
Leicester
Lincoln County Hospital
Lincoln
Royal Liverpool University Hospital
Liverpool
St Bartolomew's Hospital
London, EC1A 7BE
University College Hospital
London, NW1 2BU
King's College Hospital
London
Northwick Park Hospital
London
Royal Free Hospital
London
Maidstone Hospital
Maidstone
Derriford Hospital
Plymouth
Pontefract Hospital
Pontefract
Queen's Hospital
Romford
Tunbridge Wells Hospital
Royal Tunbridge Wells
Salisbury District Hospital
Salisbury
Musgrove Park Hospital
Taunton
Torbay Hospital
Torquay
Pinderfields Hospital
Wakefield
Sandwell Hospital
West Bromwich
Royal Hampshire County Hospital
Winchester
About this study
Official title: Subcutaneous Bortezomib, Cyclophosphamide and Rituximab (BCR) Versus Fludarabine, Cyclophosphamide and Rituximab (FCR) for Initial Therapy of Waldenstrőm's Macroglobulinaemia (WM): a Randomized Phase II Trial
The purpose of this trial is to assess tolerability and efficacy of the Bortezomib, Cyclophosphamide and Rituximab combination as initial therapy for previously untreated patients with symptomatic Waldenstrom's macroglobulinaemia.
Read the detailed description
Waldenstrom macroglobulinaemia (WM) is a low grade nonHodgkin lymphoma characterised by bone marrow infiltration and the presence of an abnormal protein in the blood (IgM paraprotein. Most patients require treatment at presentation but there is no agreed standard of first line therapy. Current treatment is unsatisfactory with responses often incomplete and slow to attain, while recurrence is inevitable.
The aim of this study is to find out whether a new combination of Bortezomib (Velcade®), Cyclophosphamide and Rituximab (MabThera), is well tolerated and effective for patients with WM. R2W is a randomised, noncomparative, phase II trial of subcutaneous bortezomib, cyclophosphamide, rituximab (BCR, experimental arm) versus fludarabine, cyclophosphamide, rituximab (FCR, control arm) for initial therapy of WM. This is a two stage trial where six patients will be treated initially with BCR to assess tolerability. If BCR is considered tolerable, a further 50 patients will be randomised between BCR and FCR (2:1) in the second stage of the trial. Patients will receive 3 cycles of treatment and then be reassessed. Those with evidence of progression will stop trial treatment. All other patients will continue with a further 3 cycles (to a total of 6) unless there is a clear clinical contraindication to further treatment.
- Conditions
- Waldenstrom's Macroglobulinaemia
- Being tested
- Bortezomib, Cyclophosphamide, Rituximab, Fludarabine
- Keywords
- Waldenstrom's macroglobulinaemia, bortezomib, cyclophosphamide, rituximab
- Medical subject headings
- Waldenstrom Macroglobulinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BortezomibDrug
Also called Velcade
1.6 mg/m2 subcutaneous bortezomib on days1, 8 and 15 of 28 days cycle
CyclophosphamideDrug
Cyclophosphamide:250 mg/sq m, oral, days 1, 8 and 15 of each cycle in the experimental arm.
Cyclophosphamide:250 mg/sq m, oral, days 1, 2 and 3 of each cycle in the control arm.
RituximabBiological
Also called MabThera
Rituximab: 375 mg/m2 i.v. infusion; days 1, 8, 15 and 22 of cycles 2 and 5 only
FludarabineDrug
Fludarabine: 40 mg/sq m, oral, days 1, 2 and 3
| Study group | Role | What they receive |
|---|---|---|
| bortezomib, cyclophosphamide, rituximab | Experimental | Bortezomib:1.6 mg/m2 s.c; days 1, 8, 15 of each cycle. Cyclophosphamide:250 mg/m2 oral; days 1, 8, 15 of each cycle. Rituximab: 375 mg/m2 i.v. infusion; days 1, 8, 15 and 22 of cycles 2 and 5 only.
Cycle repeated every 28 days. After 3 cycles of treatment, patients are reassessed and those with evidence of progression stop trial treatment. All other patients continue with further 3 cycles (to a total of 6) unless a clear clinical contradiction to further treatment exist. Receives: Drug: Bortezomib; Drug: Cyclophosphamide; Biological: Rituximab |
| fludarabine, cyclophosphamide, rituximab | Active comparator | Fludarabine:40 mg/sq m, oral, days 1,2 and 3 of each cycle. Cyclophosphamide:250 mg/sq m; oral, days 1, 2 and 3 of each cycle. Rituximab: 375 mg/sq m i.v. infusion days 1, 8, 15 and 22 of cycles 2 and 5 only.
Cycle repeated every 28 days.After 3 cycles of treatment, patients are reassessed and those with evidence of progression stop trial treatment. All other patients continue with further 3 cycles (to a total of 6) unless a clear clinical contradiction to further treatment exist. Receives: Drug: Cyclophosphamide; Biological: Rituximab; Drug: Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease response
Number and percentage of patients who achieve disease response
Measured: 6 months (end of treatment)
Secondary outcomes (4)
Toxicity of grade 3 or higher adverse event
The number and percentage of patients who experience grade 3 or higher adverse event
Measured: Up to 6 months after treatment start
Progression free survival
Time from date of randomisation to the date of first progression, relapse or death from any cause
Measured: up to 5 years after treatment start
Overall survival
Time form date of randomisation to the date of death from any cause
Measured: up to 5 years after treatment start
Quality of life (EQ-5D score)
Quality of life will be measured using patient-completed EQ-5D questionnaire
Measured: at 3 and 6 months after treatment start
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2012 (estimated)
- Study startJan 2013
- Primary completionMar 2017
- Study completion2 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Waldenstrom's MacroglobulinaemiaStudies of the same condition, open and under way.
- More trials run by University College, LondonThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rebecca Auer, Principal investigator, St. Bartholomew's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01592981
- Sponsor's protocol ID
- UCL/11/0353
- Acronym
- R2W
- Status last verified
- Jun 2021
- First submitted
- 3 May 2012
- Last updated
- 18 Jun 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Subcutaneous Bortezomib, Cyclophosphamide and Rituximab (BCR) Versus Fludarabine, Cyclophosphamide and Rituximab (FCR) for Initial Therapy of Waldenstrőm's Macroglobulinaemia (WM): a Randomized Phase II Trial
- ClinicalTrials.gov ID
- NCT01592981
- Acronym / sponsor ID
- R2W / UCL/11/0353
- Conditions
- Waldenstrom's Macroglobulinaemia
- Keywords
- Waldenstrom's macroglobulinaemia, bortezomib, cyclophosphamide, rituximab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Study start
- Jan 2013
- Primary completion
- Mar 2017 (actual)
- Study completion
- 2 Aug 2020 (actual)
- First posted
- 7 May 2012 (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.
The purpose of this trial is to assess tolerability and efficacy of the Bortezomib, Cyclophosphamide and Rituximab combination as initial therapy for previously untreated patients with symptomatic Waldenstrom's macroglobulinaemia.
Detailed description
Waldenstrom macroglobulinaemia (WM) is a low grade nonHodgkin lymphoma characterised by bone marrow infiltration and the presence of an abnormal protein in the blood (IgM paraprotein. Most patients require treatment at presentation but there is no agreed standard of first line therapy. Current treatment is unsatisfactory with responses often incomplete and slow to attain, while recurrence is inevitable.
The aim of this study is to find out whether a new combination of Bortezomib (Velcade®), Cyclophosphamide and Rituximab (MabThera), is well tolerated and effective for patients with WM. R2W is a randomised, noncomparative, phase II trial of subcutaneous bortezomib, cyclophosphamide, rituximab (BCR, experimental arm) versus fludarabine, cyclophosphamide, rituximab (FCR, control arm) for initial therapy of WM. This is a two stage trial where six patients will be treated initially with BCR to assess tolerability. If BCR is considered tolerable, a further 50 patients will be randomised between BCR and FCR (2:1) in the second stage of the trial. Patients will receive 3 cycles of treatment and then be reassessed. Those with evidence of progression will stop trial treatment. All other patients will continue with a further 3 cycles (to a total of 6) unless there is a clear clinical contraindication to further treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| bortezomib, cyclophosphamide, rituximab | Experimental | Drug: Bortezomib, Drug: Cyclophosphamide, Biological: RituximabBortezomib:1.6 mg/m2 s.c; days 1, 8, 15 of each cycle. Cyclophosphamide:250 mg/m2 oral; days 1, 8, 15 of each cycle. Rituximab: 375 mg/m2 i.v. infusion; days 1, 8, 15 and 22 of cycles 2 and 5 only. Cycle repeated every 28 days. After 3 cycles of treatment, patients are reassessed and those with evidence of progression stop trial treatment. All other patients continue with further 3 cycles (to a total of 6) unless a clear clinical contradiction to further treatment exist. |
| fludarabine, cyclophosphamide, rituximab | Active comparator | Drug: Cyclophosphamide, Biological: Rituximab, Drug: FludarabineFludarabine:40 mg/sq m, oral, days 1,2 and 3 of each cycle. Cyclophosphamide:250 mg/sq m; oral, days 1, 2 and 3 of each cycle. Rituximab: 375 mg/sq m i.v. infusion days 1, 8, 15 and 22 of cycles 2 and 5 only. Cycle repeated every 28 days.After 3 cycles of treatment, patients are reassessed and those with evidence of progression stop trial treatment. All other patients continue with further 3 cycles (to a total of 6) unless a clear clinical contradiction to further treatment exist. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age ≥ 18 years
- Confirmed diagnosis of WM (according to consensus panel / WHO criteria) with measurable IgM paraprotein
- Previously untreated disease at any stage requiring therapy at the discretion of the treating physician. Suggested criteria for initiating treatment include:
- No previous chemotherapy (prior plasma exchange and steroids are permissible)
- Performance status grade 0 - 2
Key exclusion criteria (15 listed)
- Lymphoplasmacytic lymphoma with no detectable serum IgM paraprotein
- Severe pre-existing neuropathy (> grade 2)
- Autoimmune cytopenias
- Evidence of active Hepatitis B or C infection (patients with evidence of past HepB infection may be eligible - see appendix 6)
- Serological positivity for HIV
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BortezomibAlso: Velcade1.6 mg/m2 subcutaneous bortezomib on days1, 8 and 15 of 28 days cycle | Drug | bortezomib, cyclophosphamide, rituximab |
| CyclophosphamideCyclophosphamide:250 mg/sq m, oral, days 1, 8 and 15 of each cycle in the experimental arm. Cyclophosphamide:250 mg/sq m, oral, days 1, 2 and 3 of each cycle in the control arm. | Drug | bortezomib, cyclophosphamide, rituximab, fludarabine, cyclophosphamide, rituximab |
| RituximabAlso: MabTheraRituximab: 375 mg/m2 i.v. infusion; days 1, 8, 15 and 22 of cycles 2 and 5 only | Biological | bortezomib, cyclophosphamide, rituximab, fludarabine, cyclophosphamide, rituximab |
| FludarabineFludarabine: 40 mg/sq m, oral, days 1, 2 and 3 | Drug | fludarabine, cyclophosphamide, rituximab |
Primary outcome
Disease response
Time frame: 6 months (end of treatment)
Number and percentage of patients who achieve disease response
4 secondary outcomes
Toxicity of grade 3 or higher adverse event
Time frame: Up to 6 months after treatment start
Progression free survival
Time frame: up to 5 years after treatment start
Overall survival
Time frame: up to 5 years after treatment start
Quality of life (EQ-5D score)
Time frame: at 3 and 6 months after treatment start
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 18 Jun 2021.
Related trials for Waldenstrom's Macroglobulinaemia
Not yet recruitingPhase 2
Epcoritamab as Consolidative Therapy for Waldenstr(SqrRoot)(Delta)m Macroglobulinemia (WM) Treated With a Bruton Tyrosine Kinase Inhibitor (BTKi)
Waldenstrom Macroglobulinemia
RecruitingPhase 1
A Study of ARC-02 in B-cell NHL
B-cell Non Hodgkin Lymphoma
RecruitingPhase 2
Testing the Combination of Venetoclax and Rituximab, in Comparison to the Usual Treatment (Ibrutinib Plus Rituximab or Zanubrutinib Alone) for Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma
Lymphoplasmacytic Lymphoma, Waldenstrom Macroglobulinemia
Active, not recruitingPhase 1
Copanlisib and Nivolumab in Treating Patients With Richter's Transformation or Transformed Indolent Non-Hodgkin Lymphoma
Chronic Lymphocytic Leukemia, Diffuse Large B-Cell Lymphoma
Active, not recruitingObservational study
Clinical, Laboratory and Epidemiologic Characterization of Individuals and Families at High Risk of Hematologic Cancer
Waldenstrom Macroglobulinemia, Chronic Lymphocytic Leukemia
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.
Rebecca Auer principal investigator
St. Bartholomew's Hospital
30 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 Bortezomib, Cyclophosphamide and Rituximab in people with Waldenstrom's Macroglobulinaemia, run by University College, London at 30 sites in United Kingdom.
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 12 inclusion and 15 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 18 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 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?
Disease response (time frame: 6 months (end of treatment)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Jun 2021.