Clinical trial NCT00531453: A Study to Evaluate Two Different Regimens of VELCADE in Combination With Dexamethasone, Thalidomide and Cyclophosphamide (VDT vs VDTC) in Newly Diagnosed Multiple Myeloma
Official title: A Phase 2, Randomized Study of VELCADE® (Bortezomib), Dexamethasone, and Thalidomide Versus VELCADE® (Bortezomib), Dexamethasone, Thalidomide, and Cyclophosphamide in Subjects With Previously Untreated Multiple Myeloma Who Are Candidates for Autologous Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Lead sponsor: Millennium Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
First posted: 2007-09-18
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percent of Particpants Achieving Overall Combined Complete Response (CR) Following Induction
timeFrame: all data included in clinical database as of 10 April 2009
Secondary outcomes:
measure: Percent of Participants Achieving Overall Combined Complete Response (CR) Following High-dose Chemotherapy (HDT)/Stem Cell Transplantation (SCT)
timeFrame: all data included in clinical database as of 10 April 2009
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Wilhelminenspital-1
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.