VELCADE-Thalidomide-Dexamethasone (VTD) vs Thalidomide-Dexamethasone (TD) Incorporated Into Double Autotransplantation for Untreated Multiple Myeloma (MM)
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT01134484 |
Recruitment Status : Unknown
Verified July 2012 by Michele Cavo, IRCCS Azienda Ospedaliero-Universitaria di Bologna.
Recruitment status was: Active, not recruiting
First Posted : June 2, 2010
Last Update Posted : July 20, 2012
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Multiple Myeloma | Drug: Velcade Drug: Thalidomide Drug: Dexamethasone Procedure: Peripheral Blood Stem Cell (PBSC) collection Procedure: First Autologous Transplantation Procedure: Second Autologous Transplantation | Phase 3 |
This prospective phase 3 trial is aimed at evaluating whether, in comparison with standard TD, addition of Velcade to TD increases rate of CR and nCR from 15% to 30%, respectively. For this purpose, symptomatic patients aged 18-65 years with previously untreated MM and quantifiable M-protein in serum or urine are randomized (1:1) to receive induction therapy comprising three 3-week cycles of Velcade 1.3 mg/sqm, days 1, 4, 8, 11, thalidomide 100 mg, days 1-14, cycle 1, then 200 mg daily, and dexamethasone 40 mg, days 1, 2, 4, 5, 8, 9, 11, 12, or thalidomide and dexamethasone (same schedule and dosage as in VTD). Randomization to VTD or TD is stratified according to International Staging System disease stage at diagnosis. Following induction therapy, patients in both arms receive cyclophosphamide (4 g/sqm, day 0 and granulocyte colony-stimulating factor, 10 μcg/kg/day, from day +2) to collect autologous peripheral blood stem cells (minimum threshold CD34+ cells: 4 x 10^6/kg) and two subsequent courses of stem cell-supported high dose melphalan (200 mg/sqm), 3 to 6 months apart. Upon neutrophil (≥1 x 10^9/L) and platelet (≥75 x 10^9/L) recovery following the first autotransplantation, patients receive thalidomide (100 mg daily) and dexamethasone (40 mg, days 1-4 every 4 weeks) as bridge therapy until the day before the second transplantation.
Patients initially randomized to receive VTD or TD induction therapy are planned to receive two 5-week cycles of VTD (Velcade 1.3 mg/sqm, days 1, 8, 15, 22; thalidomide 100 mg daily; dexamethasone 40 mg, days 1, 2, 8, 9, 15, 16, 22, 23) or TD (thalidomide 100 mg daily; dexamethasone 40 mg, days 1-4 and 20-23) as consolidation therapy, starting 3 months after last transplant. Maintenance therapy comprise dexamethasone 40 mg, days 1-4, repeated monthly until relapse or progression.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 480 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase 3, Prospective, Randomized Clinical Study of VELCADE-Thalidomide-Dexamethasone (VTD) Versus Thalidomide-Dexamethasone (TD) for Previously Untreated Multiple Myeloma (MM) Patients Who Are Candidates to Receive Double Autologous Transplantation |
Study Start Date : | May 2006 |
Actual Primary Completion Date : | August 2008 |
Estimated Study Completion Date : | December 2015 |
Arm | Intervention/treatment |
---|---|
Experimental: VTD |
Drug: Velcade
Other Name: Bortezomib Drug: Thalidomide
Other Name: Talidomide Drug: Dexamethasone
Other Name: Soldesam Procedure: Peripheral Blood Stem Cell (PBSC) collection
Procedure: First Autologous Transplantation
Procedure: Second Autologous Transplantation
|
Active Comparator: TD |
Drug: Thalidomide
Other Name: Talidomide Drug: Dexamethasone
Other Name: Soldesam Procedure: Peripheral Blood Stem Cell (PBSC) collection
Procedure: First Autologous Transplantation
Procedure: Second Autologous Transplantation
|
- Rate of CR+nCR to induction treatment [ Time Frame: 63 days after the start day of either TD or VTD as induction therapy ]Responses to induction therapy were reported by study investigators and centrally reassessed by study coordinator(s). Criteria are those initially proposed by the European Group for Blood and Marrow Transplantation (EBMT), with the addition of nCR (100% M-protein reduction by electrophoresis, but immunofixation-positive) and very good partial response (VGPR) (at least 90% serum and urine M-protein reduction) categories. Comparisons of response rates between treatment arms are performed using Fisher's exact test.
- Rate of CR+nCR to autotransplantation(s) and subsequent consolidation therapy [ Time Frame: 90 days after the second autologous transplantation and 70 days after the beginning of either TD or VTD as consolidation therapy ]Responses to autotransplantation(s) and consolidation therapy were reported by study investigators and centrally reassessed by study coordinator(s). Criteria are those initially proposed by the EBMT, with the addition of nCR and VGPR categories. Comparisons of response rates between treatment arms are performed using Fisher's exact test. Comparisons of response rates between treatment arms are performed using Fisher's exact test.
- Time To Progression (TTP) [ Time Frame: Average time period between the start day of either TD or VTD as induction therapy and the day of relapse or progression ]TTP is defined as time from start of induction treatment with either TD or VTD to relapse or progression, as evaluated according to EBMT criteria. Comparison of TTP between treatment arms is performed using the log-rank test; distributions are estimated using Kaplan-Meier methodology.
- Progression-Free Survival (PFS) [ Time Frame: Average time period between the start day of either TD or VTD as induction therapy and the day of relapse or progression or death, whichever occurs firstly ]PFS is defined as time from start of treatment to progression/relapse, or death, whichever occurs firstly. Comparison of PFS between treatment arms is performed using the log-rank test; distributions are estimated using Kaplan-Meier methodology.
- Overall Survival (OS) [ Time Frame: Average time period between the start day of either TD or VTD as induction therapy and the day of death, due to any cause ]OS is defined as time from start of treatment to death. Comparison of OS between treatment arms is performed using the log-rank test; distributions are estimated using Kaplan-Meier methodology.
- Safety [ Time Frame: Average time period between the start day of either TD or VTD as induction therapy and the day of any toxicity/adverse event(s) recorded during and after study drug administration ]Safety is monitored until 30 days after the last dose of study drug. Toxicities are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Rates of adverse events are compared between treatment arms using the chi-square test.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion criteria:
- Confirmed diagnosis of symptomatic MM based on standard criteria.
- No prior or current systemic therapy for MM, including steroids.
- At least 18 years and less than 65 years of age.
- Presence of quantifiable M protein in serum (e.g. greater than 1 g/dL for IgG MM, greater than 0.5 g/dL of IgA or IgD MM) or urine (e.g. greater than 200 mg/day for BJ MM).
- Karnofsky performance status (PS) at least 60%.
- Willing and able to comply with the protocol requirements.
- Agreement from both male and female patients to follow the risk management program established for the prevention of pregnancy, including double methods for contraception and beta-HCG tests for women of childbearing potential and contraception for males.
- Adequate organ function, including heart, liver, kidney (serum creatinine less than 2 mg/dL)
- Platelet count at least 70 x 10/mcL and absolute neutrophil count at least 1 x 10/mcl
Exclusion criteria:
- Diagnosis of asymptomatic MM or of MGUS based on standard criteria.
- Diagnosis of non-secretory MM.
- Diagnosis of AL Amyloidosis.
- Prior or current systemic therapy for MM, including steroids (with exception of bisphosphonates).
- Patient has received other investigational drugs within 30 days before enrollment.
- Female subjects pregnant or breastfeeding
- Patient has Grade 2 or higher peripheral neuropathy (NCI criteria).
- Patient has a prior history of thrombosis or venous thromboembolism or pulmonary embolism.
- Patient has a previous diagnosis of antiphospholipid antibodies or lupus anticoagulant, factor V Leiden mutation, prothrombin G21210A mutation, antithrombin, protein C or S deficiency.
- Patient has a clear indication to receive a specific other anti-platelet therapy (e.g. clopidogrel, ticlopidine).
- Patient has a clear indication to receive long-term anticoagulant therapy (e.g. prosthetic heart valve, atrial fibrillation).
- Active bleeding or high risk of bleeding (gastrointestinal bleeding within the past 12 months; endoscopic diagnosis of peptic ulcer disease or ulcerative esophagitis within the past 6 months unless there is documented endoscopic evidence of healing; intracranial bleeding within the past year; amyloidosis; known bleeding diathesis).
- Seropositive for HIV, or active hepatitis A, B or C infection.
- Poorly controlled hypertension or diabetes mellitus (if receiving antidiabetic agents, subjects must be on a stable dose for at least 3 months before the start of therapy) or other serious medical or psychiatric conditions that could interfere with adherence to or completion of this study.
- Patient has hypersensitivity to bortezomib, boron or mannitol.
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study
- Previous or concurrent malignancies at other sites, with the exception of appropriately treated localized epithelial skin or cervical cancer. Patients with remote histories (>5 years) of other cured tumors may be entered.
- Receipt of extensive radiation therapy, systemic chemotherapy, or other antineoplastic therapy within 4 weeks before enrolment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01134484
Italy | |
AOU di Bologna Policlinico S.Orsola-Malpighi, UO di Ematologia | |
Bologna, Italy, 40138 |
Principal Investigator: | Michele Cavo, MD | IRCCS Azienda Ospedaliero-Universitaria di Bologna |
Responsible Party: | Michele Cavo, MD, IRCCS Azienda Ospedaliero-Universitaria di Bologna |
ClinicalTrials.gov Identifier: | NCT01134484 |
Other Study ID Numbers: |
MM-BO2005 2005-003723-39 ( EudraCT Number ) 26866138-MMY-3006 ( Other Grant/Funding Number: Janssen-Cilag SpA ) |
First Posted: | June 2, 2010 Key Record Dates |
Last Update Posted: | July 20, 2012 |
Last Verified: | July 2012 |
autologous stem cell transplantation complete remission bortezomib |
thalidomide progression free survival induction and consolidation therapy |
Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Thalidomide |
Dexamethasone Bortezomib Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents Immunosuppressive Agents Immunologic Factors |