Clinical trial NCT00813150: Study of Bortezomib and Dexamethasone With or Without Cyclophosphamide in Patients With Relapsed or Not Controllable Multiple Myeloma
Official title: Randomized Phase III Study on Bortezomib and Low-Dose Dexamethasone With or Without Continuous Low-Dose Oral Cyclophosphamide for Primary Refractory or Relapsed Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: Multiple myeloma
Bortezomib
Dexamethasone
Cyclophosphamide
Oncology
Lead sponsor: Janssen-Cilag G.m.b.H
Sponsor class: INDUSTRY
First posted: 2008-12-22
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare bortezomib, dexamethasone and cyclophosphamide to bortezomib and dexamethasone alone for primary refractory or relapsed multiple myeloma.

Detailed description: This is a prospective, multi-centre, randomized (the study drug is assigned by chance), controlled, open-label (all people involved in the study know the identity of the assigned drug), parallel (each group of patients will be treated at the same time) group phase III study to determine the efficacy of the standard therapy of bortezomib and low dose dexamethasone in combination with or without continuous low dose oral cyclophosphamide for primary refractory or relapsed myeloma patients (1st - 3rd relapse). The study will consist of screening period, which may last from day -14 until day -1 before application of the first dose of bortezomib (on cycle 1, day 1), treatment phase begins on cycle 1 day 1 and continues until completion or discontinuation of all study drugs and follow-up phase. All patients will be followed up after end of treatment regardless of their response. Eligible patients will be randomized in 1:1 ratio to receive either treatment arms (Group A: receiving bortezomib plus dexamethasone or Group B receiving bortezomib plus dexamethasone plus cyclophosphamide). Patients will receive up to eight 3-weeks treatment cycles, unless they experience either unacceptable toxicity or if the patients request to withdraw from the study. The maximum number of cycles is dependent on patient response and investigator's discretion. It is recommended that patients with a confirmed complete response (CR) receive 2 additional cycles beyond a confirmation. Patients who do not achieve a CR but a partial response will receive a total of 8 cycles. For patients achieving stable disease it is within the investigator's discretion to continue study treatment beyond 6 cycles, after discussion with the sponsor. After completion of treatment the patients will be followed up every 12 weeks for up to 72 weeks. If the study is still ongoing a further follow up period will be done every 26 weeks until study end, or until the patient reaches progressive disease or start of alternative anti-myeloma therapy, if earlier. In case progressive disease (PD) has already been established during the treatment phase the patients will not enter the follow-up phase. In case of PD or start of alternative anti-myeloma treatment before the end of study the follow-up phase will be discontinued for the patient but the date of death of the patient will be documented (if applicable) before the end of study.

Eligibility criteria: Inclusion Criteria:

* Previously diagnosed with multiple myeloma
* Primary refractory multiple myeloma or relapsed following 1 to 3 previous lines of therapy
* Karnofsky performance status must be equal to 60 percentage (ie, better or equal performance than requiring some help and taking care of most personal requirements)
* Has life expectancy estimated at screening must be of at least 6 months
* Agrees to protocol-defined use of effective contraception

Exclusion Criteria:

* Not received more than three previous lines of therapy for multiple myeloma
* Not received nitrosoureas or any other chemotherapy or immunotherapy or antibody therapy for multiple myeloma within 6 to 8 weeks before enrolment. Plasmapheresis must not be applied within 2 weeks before enrolment
* Patients with peripheral neuropathy or neuropathic pain of Grade 2 or greater intensity
* Patients with poorly controlled cardio vascular, vascular, pulmonary, gastro-intestinal, endocrine, neurological, psychiatric, hepatic, renal or metabolic diseases or hematological disorders
* Not have oligosecretory or non-secretory multiple myeloma

Primary outcomes:
measure: Time to Progression of Disease
timeFrame: From the date of randomization until the disease progression or participant's death from any cause whichever occurred first, as assessed up to 72 weeks after end of treatment visit (ie, 46 days after last dose of study medication)
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: From the date of randomization until the disease progression or participant's death from any cause whichever occured first, as assessed up to 72 weeks after end of treatment visit (ie, 46 days after last dose of study medication)
measure: Overall Survival (OS)
timeFrame: From the date of randomization until Month 49
measure: Overall Response Rate (ORR) - International Myeloma Working Group (IMWG) Response Criteria
timeFrame: Up to 46 days after last bortezomib dose, or as soon as possible after early discontinuation of study treatment or before start of alternative anti-myeloma therapy
Other outcomes:
Locations:
city: Augsburg
country: Germany
city: Berlin
country: Germany
city: Bielefeld
country: Germany
city: Bremerhaven
country: Germany
city: Darmstadt
country: Germany
city: Donauwörth
country: Germany
city: Dresden
country: Germany
city: Frankfurt
country: Germany
city: Halle
country: Germany
city: Hamburg
country: Germany
city: Hamm
country: Germany
city: Hannover
country: Germany
city: Hildesheim
country: Germany
city: Hof
country: Germany
city: Koblenz
country: Germany
city: Köln
country: Germany
city: Lebach
country: Germany
city: Leer
country: Germany
city: Lübeck
country: Germany
city: Magdeburg
country: Germany
city: Mannheim
country: Germany
city: Moers
country: Germany
city: München
country: Germany
city: Münster
country: Germany
city: Neunkirchen
country: Germany
city: Offenburg
country: Germany
city: Oldenburg
country: Germany
city: Osnabrück
country: Germany
city: Passau
country: Germany
city: Porta Westfalica
country: Germany
city: Ravensburg
country: Germany
city: Rostock
country: Germany
city: Saarbrücken
country: Germany
city: Singen
country: Germany
city: Stuttgart
country: Germany
city: Velbert
country: Germany
city: Weiden
country: Germany
city: Wiesbaden
country: Germany
city: Würselen
country: Germany
city: Würzburg
country: Germany
Study officials:
affiliation: Janssen-Cilag G.m.b.H
name: Janssen-Cilag G.m.b.H, Germany Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Kropff M, Vogel M, Bisping G, Schlag R, Weide R, Knauf W, Fiechtner H, Kojouharoff G, Kremers S, Berdel WE. Bortezomib and low-dose dexamethasone with or without continuous low-dose oral cyclophosphamide for primary refractory or relapsed multiple myeloma: a randomized phase III study. Ann Hematol. 2017 Nov;96(11):1857-1866. doi: 10.1007/s00277-017-3065-z. Epub 2017 Sep 14.