A Study to Evaluate Two Different Regimens of VELCADE in Combination With Dexamethasone, Thalidomide and Cyclophosphamide (VDT vs VDTC) in Newly Diagnosed Multiple Myeloma

NCT ID: NCT00531453

Last Updated: 2012-01-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-31
• Study Completion Date: 2009-05-31

Brief Summary

The purpose of this Phase 2 randomized study is to evaluate the efficacy and safety of treatment with a regimen of VELCADE, dexamethasone, and thalidomide (VDT) or VELCADE, dexamethasone, thalidomide, and cyclophosphamide (VDTC) in subjects with newly diagnosed symptomatic multiple myeloma who have received no prior treatment and are candidates to receive high-dose therapy and autologous bone marrow/stem cell transplantation.

Conditions

Multiple Myeloma

Study Design

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

Study Groups

1

bortezomib, dexamethasone, and thalidomide

Group Type: EXPERIMENTAL

bortezomib, dexamethasone, and thalidomide

Intervention Type: DRUG

VELCADE (bortezomib) twice weekly for 4 cycles (4 doses per cycle), prior to high-dose chemotherapy (HDT) and stem cell transplantation(SCT). Subjects will receive VELCADE 1.3 mg/m2 as an intravenous (i.v.) bolus injection on Days 1,4,8, and 11, followed by a 10 day rest period (Days 12 to 21)

Dexamethasone 40 mg/day will be given by mouth (p.o.) on Days 1-4 and Days 9-12 in each of 4 cycles.

Thalidomide will be given by mouth (p.o.)every day, starting on Day 1 of Cycle 1 (e.g. the same day of the first dose of VELCADE) and continuing until Day 21 of Cycle 4 at a dose of 100 mg/day (bedtime).

2

bortezomib, dexamethasone, thalidomide, and cyclophosphamide

Group Type: EXPERIMENTAL

bortezomib, dexamethasone, thalidomide, and cyclophosphamide

Intervention Type: DRUG

VELCADE (bortezomib) twice weekly for 4 cycles (4 doses per cycle), prior to high-dose chemotherapy(HDT)and stem cell transplantation(SCT). Subjects will receive VELCADE 1.3 mg/m2 as an intravenous (i.v.) bolus injection on Days 1,4,8, and 11, followed by a 10 day rest period (Days 12 to 21).

Dexamethasone 40 mg/day will be given by mouth (p.o.) on Days 1-4 and Days 9-12 in each of 4 cycles.

Thalidomide will be given by mouth (p.o.) every day, starting on Day 1 of Cycle 1 (e.g., the same day of the first dose of VELCADE) and continuing until Day 21 of Cycle 4 at a dose of 100 mg/day (bedtime).

Cyclophosphamide will be given as an intravenous (i.v.) dose of 400 mg/m2 on Day 1 and Day 8 of each 3-week cycle, for a total of 4 cycles.

Interventions

bortezomib, dexamethasone, and thalidomide

VELCADE (bortezomib) twice weekly for 4 cycles (4 doses per cycle), prior to high-dose chemotherapy (HDT) and stem cell transplantation(SCT). Subjects will receive VELCADE 1.3 mg/m2 as an intravenous (i.v.) bolus injection on Days 1,4,8, and 11, followed by a 10 day rest period (Days 12 to 21)

Dexamethasone 40 mg/day will be given by mouth (p.o.) on Days 1-4 and Days 9-12 in each of 4 cycles.

Thalidomide will be given by mouth (p.o.)every day, starting on Day 1 of Cycle 1 (e.g. the same day of the first dose of VELCADE) and continuing until Day 21 of Cycle 4 at a dose of 100 mg/day (bedtime).

Intervention Type: DRUG

bortezomib, dexamethasone, thalidomide, and cyclophosphamide

VELCADE (bortezomib) twice weekly for 4 cycles (4 doses per cycle), prior to high-dose chemotherapy(HDT)and stem cell transplantation(SCT). Subjects will receive VELCADE 1.3 mg/m2 as an intravenous (i.v.) bolus injection on Days 1,4,8, and 11, followed by a 10 day rest period (Days 12 to 21).

Dexamethasone 40 mg/day will be given by mouth (p.o.) on Days 1-4 and Days 9-12 in each of 4 cycles.

Thalidomide will be given by mouth (p.o.) every day, starting on Day 1 of Cycle 1 (e.g., the same day of the first dose of VELCADE) and continuing until Day 21 of Cycle 4 at a dose of 100 mg/day (bedtime).

Cyclophosphamide will be given as an intravenous (i.v.) dose of 400 mg/m2 on Day 1 and Day 8 of each 3-week cycle, for a total of 4 cycles.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female between ≥18 and ≤70 years
• Patient is a candidate for HDT combined with an autologous SCT
• Karnofsky Performance Status score of ≥60%
• Multiple myeloma diagnosed according to the following standard criteria AND requiring systemic therapy:
• Presence of M-component in serum and/or urine, plus clonal plasma cells in the bone marrow and/or a documented clonal plasmacytoma
• PLUS 1 or more of the following:

1. Calcium elevation (>11.5 mg/dL or >2.65 mmol/L)

2. Renal insufficiency (creatinine >2 mg/dL or >177 umol/L)

3. Anemia (hemoglobin <10 g/dL [<12.5 mmol/L] or at least 2 mg/dL [1.25 mmol/L] below normal)

4. Bone disease (lytic lesions or osteopenia)

• AND fulfill criteria for measurable disease, as defined by at least 1 of the following 3 measurements:

1. Serum M-protein ≥1 g/dL (≥10 g/L)

2. Urine M-protein ≥200 mg/24 h

3. Serum free light chain (FLC) assay: Involved FLC level ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal

• Women of childbearing potential must agree to use 2 methods of contraception.
• Males must agree to use barrier contraception.
• Subjects (or their legally acceptable representatives) must have signed an informed consent document.
• To participate in the optional pharmacogenomic component of this study, subjects (or their legally acceptable representative) must have signed the informed consent form. Refusal to consent for this component does not exclude a subject from participation in the clinical study.

Exclusion Criteria

• Diagnosis of smoldering OR non-secretory multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS).
• Diagnosis of Waldenström's disease or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.
• Prior or current systemic therapy for multiple myeloma including steroids.
• Radiation therapy and/or plasmapheresis within 15 days before randomization.
• History of allergic reaction attributable to compounds being given (VELCADE, thalidomide, dexamethasone, and/or cyclophosphamide) or compounds containing boron or mannitol.
• Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0.
• Uncontrolled or severe cardiovascular disease
• Concurrent medical condition or disease (e.g., active systemic infection, uncontrolled diabetes) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study.
• Use of any investigational drugs within 30 days before randomization
• Pregnant or lactating women: A serum β-hCG pregnancy test must be performed at the Screening visit for female subjects of childbearing potential.
• Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

INDUSTRY

Sponsor Role: collaborator

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

Wilhelminenspital-1

Vienna, Vienna, Austria

Countries

Austria

References

Ludwig H; Viterbo L; Greil R; Masszi T; Spicka I; Shpilberg O; Hajek R; Dmoszynska A; Cakana A; Enny C; Feng H; van de Velde H; and Harousseau J-L. Bortezomib, Thalidomide, and Dexamethasone (VTD) Versus VTD Plus Cyclophosphamide as Induction Therapy in Previously Untreated Multiple Myeloma Patients Eligible for HDT-ASCT: A Randomized Phase 2 Trial. Blood (ASH Annual Meeting Abstracts), Nov 2009; 114: 2312.

Reference Type: RESULT

Ludwig H, Greil R, Masszi T, Spicka I, Shpilberg O, Hajek R, Dmoszynska A, Paiva B, Vidriales MB, Esteves G, Stoppa AM, Robinson D Jr, Chaturvedi S, Ataman O, Enny C, Feng H, van de Velde H, Viterbo L. Bortezomib, thalidomide and dexamethasone, with or without cyclophosphamide, for patients with previously untreated multiple myeloma: 5-year follow-up. Br J Haematol. 2015 Nov;171(3):344-54. doi: 10.1111/bjh.13582. Epub 2015 Jul 7.

Reference Type: DERIVED

PMID: 26153365 (View on PubMed)

Ludwig H, Viterbo L, Greil R, Masszi T, Spicka I, Shpilberg O, Hajek R, Dmoszynska A, Paiva B, Vidriales MB, Esteves G, Stoppa AM, Robinson D Jr, Ricci D, Cakana A, Enny C, Feng H, van de Velde H, Harousseau JL. Randomized phase II study of bortezomib, thalidomide, and dexamethasone with or without cyclophosphamide as induction therapy in previously untreated multiple myeloma. J Clin Oncol. 2013 Jan 10;31(2):247-55. doi: 10.1200/JCO.2011.39.5137. Epub 2012 Oct 22.

Reference Type: DERIVED

PMID: 23091109 (View on PubMed)

Other Identifiers

26866138-MMY-2043

Identifier Type: -

Identifier Source: org_study_id