Randomised Trial in Waldenstrom's Macroglobulinaemia

NCT ID: NCT01592981

Last Updated: 2021-06-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-01-31

Study Completion Date

2020-08-02

Brief Summary

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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

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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

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Waldenstrom's Macroglobulinaemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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bortezomib, cyclophosphamide, rituximab

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.

Group Type EXPERIMENTAL

Bortezomib

Intervention Type DRUG

1.6 mg/m2 subcutaneous bortezomib on days1, 8 and 15 of 28 days cycle

Cyclophosphamide

Intervention Type DRUG

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.

Rituximab

Intervention Type BIOLOGICAL

Rituximab: 375 mg/m2 i.v. infusion; days 1, 8, 15 and 22 of cycles 2 and 5 only

fludarabine, cyclophosphamide, rituximab

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.

Group Type ACTIVE_COMPARATOR

Cyclophosphamide

Intervention Type DRUG

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.

Rituximab

Intervention Type BIOLOGICAL

Rituximab: 375 mg/m2 i.v. infusion; days 1, 8, 15 and 22 of cycles 2 and 5 only

Fludarabine

Intervention Type DRUG

Fludarabine: 40 mg/sq m, oral, days 1, 2 and 3

Interventions

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Bortezomib

1.6 mg/m2 subcutaneous bortezomib on days1, 8 and 15 of 28 days cycle

Intervention Type DRUG

Cyclophosphamide

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.

Intervention Type DRUG

Rituximab

Rituximab: 375 mg/m2 i.v. infusion; days 1, 8, 15 and 22 of cycles 2 and 5 only

Intervention Type BIOLOGICAL

Fludarabine

Fludarabine: 40 mg/sq m, oral, days 1, 2 and 3

Intervention Type DRUG

Other Intervention Names

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Velcade MabThera

Eligibility Criteria

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Inclusion Criteria

* 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
* 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

Exclusion Criteria

* 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
* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University College, London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Rebecca Auer

Role: PRINCIPAL_INVESTIGATOR

St. Bartholomew's Hospital

Locations

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Basingstoke & North Hampshire Hospital

Basingstoke, , United Kingdom

Site Status

Royal United Hospital

Bath, , United Kingdom

Site Status

Birmingham Heartlands Hospital

Birmingham, , United Kingdom

Site Status

City Hospital

Birmingham, , United Kingdom

Site Status

Pilgrim Hospital

Boston, , United Kingdom

Site Status

Colchester General Hospital

Colchester, , United Kingdom

Site Status

Darent Valley Hospital

Dartford, , United Kingdom

Site Status

Dewsbury and District Hospital

Dewsbury, , United Kingdom

Site Status

Royal Devon and Exeter Hospital

Exeter, , United Kingdom

Site Status

Grantham and District Hospital

Grantham, , United Kingdom

Site Status

St James University Hospital

Leeds, , United Kingdom

Site Status

Leicester Royal Infirmary

Leicester, , United Kingdom

Site Status

Lincoln County Hospital

Lincoln, , United Kingdom

Site Status

Royal Liverpool University Hospital

Liverpool, , United Kingdom

Site Status

St Bartolomew's Hospital

London, , United Kingdom

Site Status

University College Hospital

London, , United Kingdom

Site Status

King's College Hospital

London, , United Kingdom

Site Status

Northwick Park Hospital

London, , United Kingdom

Site Status

Royal Free Hospital

London, , United Kingdom

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Maidstone Hospital

Maidstone, , United Kingdom

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Derriford Hospital

Plymouth, , United Kingdom

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Pontefract Hospital

Pontefract, , United Kingdom

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Queen's Hospital

Romford, , United Kingdom

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Tunbridge Wells Hospital

Royal Tunbridge Wells, , United Kingdom

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Salisbury District Hospital

Salisbury, , United Kingdom

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Musgrove Park Hospital

Taunton, , United Kingdom

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Torbay Hospital

Torquay, , United Kingdom

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Pinderfields Hospital

Wakefield, , United Kingdom

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Sandwell Hospital

West Bromwich, , United Kingdom

Site Status

Royal Hampshire County Hospital

Winchester, , United Kingdom

Site Status

Countries

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United Kingdom

Other Identifiers

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UCL/11/0353

Identifier Type: -

Identifier Source: org_study_id

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