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

NCT00813150 | Completed Phase 3 Results

• 3 other identifiers: CR01524726866138MMY30222008-003213-27
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 40

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.

Conditions

Multiple Myeloma

Keywords

Multiple myeloma; Bortezomib; Dexamethasone; Cyclophosphamide; Oncology

Outcome Measures

Primary Outcomes (1)

• Time to Progression of Disease

  'Median time to progression of disease is assessed according to International Myeloma Working Group (IMWG) criteria or death from any cause. IMWG criteria: increase of \>=25% from lowest level in Serum M-component or (the absolute increase must be \>=0.5 gram per deciliter \[g/dL\]); Urine M component or (the absolute increase must be \>=200 milligram per 24 hour. Only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain levels. The absolute increase \>10 mg/dL. Bone marrow plasma cell percentage \>=10%. Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing. Development of hypercalcemia. Participants who died or dropped out due to any reason without progression will be censored with the day of death or drop-out, respectively and who are alive at the end of the study without any progression was censored with the last available date.

  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 (3)

• Progression-Free Survival (PFS)

  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)

• Overall Survival (OS)

  From the date of randomization until Month 49

• Overall Response Rate (ORR) - International Myeloma Working Group (IMWG) Response Criteria

  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

Study Arms (2)

Vd (bortezomib + dexamethasone)

EXPERIMENTAL

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.

Drug: Dexamethasone; Drug: Bortezomib

Vcd (bortezomib + low-dose dexamethasone + cyclophosphamide)

ACTIVE COMPARATOR

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.

Drug: Dexamethasone; Drug: Bortezomib; Drug: Cyclophosphamide

Interventions

Dexamethasone 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.

Vcd (bortezomib + low-dose dexamethasone + cyclophosphamide); Vd (bortezomib + dexamethasone)

Bortezomib 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); Vd (bortezomib + dexamethasone)

Cyclophosphamide 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.

Vcd (bortezomib + low-dose dexamethasone + cyclophosphamide)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen-Cilag G.m.b.H: lead

Study Sites (40)

Unknown Facility

Augsburg, Germany

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Berlin, Germany

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Bielefeld, Germany

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Bremerhaven, Germany

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Cologne, Germany

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Darmstadt, Germany

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Donauwörth, Germany

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Dresden, Germany

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Frankfurt, Germany

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Halle, Germany

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Hamburg, Germany

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Hamm, Germany

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Hanover, Germany

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Hildesheim, Germany

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Hof, Germany

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Koblenz, Germany

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Lebach, Germany

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Leer, Germany

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Lübeck, Germany

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Magdeburg, Germany

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Mannheim, Germany

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Moers, Germany

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München, Germany

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Münster, Germany

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Neunkirchen, Germany

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Offenburg, Germany

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Oldenburg, Germany

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Osnabrück, Germany

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Passau, Germany

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Porta Westfalica, Germany

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Ravensburg, Germany

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Rostock, Germany

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Saarbrücken, Germany

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Singen, Germany

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Stuttgart, Germany

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Velbert, Germany

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Weiden, Germany

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Wiesbaden, Germany

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Würselen, Germany

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Unknown Facility

Würzburg, Germany

Location

Related Publications (1)

• 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.

  PMID: 28905189 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms

Interventions

Dexamethasone; Bortezomib; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Therapeutic Areas Director
• Organization: Jan-Cil Germany

ClinicalTrialDisclosure@its.jnj.com

Study Officials

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

  Janssen-Cilag G.m.b.H

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2008
• First Posted: December 22, 2008
• Study Start: January 1, 2009
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: August 15, 2014
• Results First Posted: August 15, 2014

Record last verified: 2014-07

Locations

DE (40)