Randomised Trial in Waldenstrom's Macroglobulinaemia (R2W)

This study is currently recruiting participants.
Verified March 2013 by University College, London
Sponsor:
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT01592981
First received: May 3, 2012
Last updated: March 26, 2013
Last verified: March 2013

May 3, 2012
March 26, 2013
January 2013
July 2016   (final data collection date for primary outcome measure)
Disease response [ Time Frame: 6 months (end of treatment) ] [ Designated as safety issue: No ]
Number and percentage of patients who achieve disease response
Same as current
Complete list of historical versions of study NCT01592981 on ClinicalTrials.gov Archive Site
  • Toxicity [ Time Frame: Up to 6 months after treatment start ] [ Designated as safety issue: Yes ]
    The number and percentage of patients who experience grade 3 or higher adverse event
  • Progression free survival [ Time Frame: up to 5 years after treatment start ] [ Designated as safety issue: No ]
    Time from date of randomisation to the date of first progression, relapse or death from any cause
  • Overall survival [ Time Frame: up to 5 years after treatment start ] [ Designated as safety issue: No ]
    Time form date of randomisation to the date of death from any cause
  • Quality of life [ Time Frame: at 3 and 6 months after treatment start ] [ Designated as safety issue: No ]
    Quality of life will be measured using patient-completed EQ-5D questionnaire
Same as current
Not Provided
Not Provided
 
Randomised Trial in Waldenstrom's Macroglobulinaemia
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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Waldenstrom's Macroglobulinaemia
  • Drug: Bortezomib
    1.6 mg/m2 subcutaneous bortezomib on days1, 8 and 15 of 28 days cycle
    Other Name: Velcade
  • 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.

  • Biological: Rituximab
    Rituximab: 375 mg/m2 i.v. infusion; days 1, 8, 15 and 22 of cycles 2 and 5 only
    Other Name: MabThera
  • Drug: Fludarabine
    Fludarabine: 40 mg/sq m, oral, days 1, 2 and 3
  • Experimental: 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.

    Interventions:
    • Drug: Bortezomib
    • Drug: Cyclophosphamide
    • Biological: Rituximab
  • Active Comparator: 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.

    Interventions:
    • Drug: Cyclophosphamide
    • Biological: Rituximab
    • Drug: Fludarabine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
56
July 2021
July 2016   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: R2W Trial Coordinator +44 207 679 9860 ctc.r2w@ucl.ac.uk
United Kingdom
 
NCT01592981
UCL/11/0353
Yes
University College, London
University College, London
Not Provided
Not Provided
University College, London
March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP