Study of Bortezomib and Dexamethasone With or Without Cyclophosphamide in Patients With Relapsed or Not Controllable Multiple Myeloma

NCT ID: NCT00813150

Last Updated: 2014-08-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2013-01-31

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vd (bortezomib + dexamethasone)

Participants received bortezomib at a dose of 1.3 mg/m² body surface area (BSA) for eight 3-week cycles. Within each cycle it was administered twice weekly (on Days 1, 4, 8, and 11) followed by a 10-day rest period (Days 12 through 21). They received single oral doses of 20 mg dexamethasone on Days

1 and 2, 4 and 5, 8 and 9, and 11 and 12 of each cycle.

Group Type: EXPERIMENTAL

Dexamethasone

Intervention Type: DRUG

Type=exact number, number=20, unit=mg, form=tablet, route=oral. The patients will receive 20 mg of dexamethasone on days 1+2,4+5,8+9,11+12 for 21 days for 8 cycles.

Bortezomib

Intervention Type: DRUG

Type=exact number, number=1.3, unit=mg, form=injection, route=intravenous. The patients will receive 1.3mg/m2 on days 1,4,8,11 for 21 days for 8 cycles.

Vcd (bortezomib + low-dose dexamethasone + cyclophosphamide)

Participants received bortezomib at a dose of 1.3 mg/m² body surface area (BSA) for eight 3-week cycles. Within each cycle it was administered twice weekly (on Days 1, 4, 8, and 11) followed by a 10-day rest period (Days 12 through 21). They received single oral doses of 20 mg dexamethasone on Days 1 and 2, 4 and 5, 8 and 9, and 11 and 12 of each cycle and single oral doses of 50 mg cyclophosphamide on a once daily basis from Day 1, Cycle 1 continuously until Day 21, Cycle 8.

Group Type: ACTIVE_COMPARATOR

Dexamethasone

Intervention Type: DRUG

Type=exact number, number=20, unit=mg, form=tablet, route=oral. The patients will receive 20 mg of dexamethasone on days 1+2,4+5,8+9,11+12 for 21 days for 8 cycles.

Bortezomib

Intervention Type: DRUG

Type=exact number, number=1.3, unit=mg, form=injection, route=intravenous. The patients will receive 1.3mg/m2 on days 1,4,8,11 for 21 days for 8 cycles.

Cyclophosphamide

Intervention Type: DRUG

Type=exact number, number=50, unit=mg, form=tablet, route=oral. The patients will receive 50 mg of cyclophosphamide once daily continuously from cycle 1 to 8.

Interventions

Dexamethasone

Type=exact number, number=20, unit=mg, form=tablet, route=oral. The patients will receive 20 mg of dexamethasone on days 1+2,4+5,8+9,11+12 for 21 days for 8 cycles.

Intervention Type: DRUG

Bortezomib

Type=exact number, number=1.3, unit=mg, form=injection, route=intravenous. The patients will receive 1.3mg/m2 on days 1,4,8,11 for 21 days for 8 cycles.

Intervention Type: DRUG

Cyclophosphamide

Type=exact number, number=50, unit=mg, form=tablet, route=oral. The patients will receive 50 mg of cyclophosphamide once daily continuously from cycle 1 to 8.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen-Cilag G.m.b.H

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen-Cilag G.m.b.H, Germany Clinical Trial

Role: STUDY_DIRECTOR

Janssen-Cilag G.m.b.H

Locations

Augsburg, , Germany

Berlin, , Germany

Bielefeld, , Germany

Bremerhaven, , Germany

Cologne, , Germany

Darmstadt, , Germany

Donauwörth, , Germany

Dresden, , Germany

Frankfurt, , Germany

Halle, , Germany

Hamburg, , Germany

Hamm, , Germany

Hanover, , Germany

Hildesheim, , Germany

Hof, , Germany

Koblenz, , Germany

Lebach, , Germany

Leer, , Germany

Lübeck, , Germany

Magdeburg, , Germany

Mannheim, , Germany

Moers, , Germany

München, , Germany

Münster, , Germany

Neunkirchen, , Germany

Offenburg, , Germany

Oldenburg, , Germany

Osnabrück, , Germany

Passau, , Germany

Porta Westfalica, , Germany

Ravensburg, , Germany

Rostock, , Germany

Saarbrücken, , Germany

Singen, , Germany

Stuttgart, , Germany

Velbert, , Germany

Weiden, , Germany

Wiesbaden, , Germany

Würselen, , Germany

Würzburg, , Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 28905189 (View on PubMed)

Other Identifiers

26866138MMY3022

Identifier Type: OTHER

Identifier Source: secondary_id

2008-003213-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR015247

Identifier Type: -

Identifier Source: org_study_id