Overview

This trial is active, not recruiting.

Condition waldenstrom's macroglobulinaemia
Treatments bortezomib, cyclophosphamide, rituximab, fludarabine
Phase phase 2
Targets CD20, proteasome
Sponsor University College, London
Start date January 2013
End date March 2017
Trial size 60 participants
Trial identifier NCT01592981, UCL/11/0353

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(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.
bortezomib Velcade
1.6 mg/m2 subcutaneous bortezomib on days1, 8 and 15 of 28 days cycle
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.
rituximab MabThera
Rituximab: 375 mg/m2 i.v. infusion; days 1, 8, 15 and 22 of cycles 2 and 5 only
(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.
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.
rituximab MabThera
Rituximab: 375 mg/m2 i.v. infusion; days 1, 8, 15 and 22 of cycles 2 and 5 only
fludarabine
Fludarabine: 40 mg/sq m, oral, days 1, 2 and 3

Primary Outcomes

Measure
Disease response
time frame: 6 months (end of treatment)

Secondary Outcomes

Measure
Toxicity
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
time frame: at 3 and 6 months after treatment start

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

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
Principal investigator Rebecca Auer
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.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by University College, London.