A Pilot Study of the Combination of Melphalan, Bortezomib, Thalidomide and Dexamethasone (MEL-VTD)

UARK 2007-01, A Phase II Pilot Study of the Combination of Melphalan, Bortezomib, Thalidomide and Dexamethasone (MEL-VTD) and Autologous Transplantation for Patients Relapsing or Progressing After Tandem Transplantation

In this study, researchers want to find out if using the VTD regimen, along with higher doses melphalan, in subjects who have relapsed or progressed after previous transplant(s), can be given safely to subjects who have failed previous transplant(s).

Study Overview

• Status: Withdrawn
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Melphalan, Velcade, Thalidomide, Dexamethasone

Detailed Description

Autologous transplant is now considered a standard treatment for many patients with multiple myeloma. An autologous transplant is a procedure in which stem cells are removed from a patient and then given back to the patient following intensive treatment. Doctors remove healthy stem cells from a patient's circulating blood system and store them before the patient receives high-dose chemotherapy. The stem cells are then returned to the patient, where they can produce new blood cells to replace cells destroyed by the treatment. The drug usually used before transplant is melphalan alone in 1 or 2 high doses. In past studies conducted at UAMS, researchers have shown that a chemotherapy treatment regimen called "VTD" is effective in patients with multiple myeloma who have failed previous treatments. VTD is a combination of drugs consisting of VelcadeTM (also known as bortezomib), Thalidomide, and Dexamethasone. In this study, researchers want to find out if using the VTD regimen, along with higher doses melphalan, in subjects who have relapsed or progressed after previous transplant(s) can be given safely to subjects who have failed previous transplant(s).

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• History of histologically documented MM with relapsed or progressive disease after either scheduled tandem or one autologous transplantation.
• Patient has measurable disease in which to capture response.
• Performance status of 2 as per Zubroid scale, unless PS of 3-4 based solely on bone pain.
• Patients must have a platelet count 75,000/μL, and an ANC of at least 1,000/μL.
• Patients must have adequate renal function defined as serum creatinine < 2.5 mg/dL.
• Patients must have adequate hepatic function defined as serum transaminases and direct bilirubin < 2 x the upper limit of normal.
• Pregnant or nursing women may not participate. Women of childbearing potential must have a negative pregnancy documented within one week of registration. Women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
• Male or female adults of at least 18 years of age.
• Patients must have signed an IRB-approved written informed consent form and demonstrate willingness to meet follow-up schedule and study procedure obligations.

Exclusion Criteria:

• Chemotherapy or radiotherapy received within the previous 2 weeks.
• Significant neurotoxicity, defined as grade > 2 neurotoxicity per NCI Common Toxicity Criteria (See Appendix).
• Platelet count < 75,000/mm3, or ANC < 1,000/μl.
• Clinically significant hepatic dysfunction as noted by bilirubin or AST > 3 times the upper normal limit or clinically significant concurrent hepatitis.
• New York Hospital Association (NYHA) Class III or Class IV heart failure.
• Myocardial infarction within the last 6 months.
• Uncontrolled, active infection requiring IV antibiotics.
• Patients with a history of treatment for clinically significant ventricular cardiac arrhythmias.
• Poorly controlled hypertension, diabetes mellitus, or other serious or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol.
• Pregnant or potential for pregnancy. Women of childbearing potential will have a pregnancy test at screening, and will be required to use a medically approved contraceptive method.
• Breast-feeding women may not participate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: VDT and Melphalan; To find out if three drugs, bortezomib, thalidomide, and dexamethasone in addition to high doses of melphalan (M-VTD) and autologous transplant can be given safely and effectively to subjects who have failed previous regimens with transplant(s).

Drug: Melphalan, Velcade, Thalidomide, Dexamethasone; To assess, in patients with one or two prior auto transplants, the efficacy of a high-dose combination chemotherapy with MEL 300 (in 3 fractions of 100 mg/m2 on days -7, -4, -1) plus VTD (Velcade = bortezomib 1.3 mg/m2 on days -7, -4, -1; Thalidomide 200 mg/d on days -1 through -7; Dexamethasone 40 mg on days -7, -6, -4, -3, -1, 0) followed by autologous peripheral blood stem cell (PBSC) infusion of a minimum dose of 3 million CD34 cells/kg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VTD regimen with melphalan	To find out if using the VTD regimen, along with higher doses melphalan, in subjects who have relapsed or progressed after previous transplant(s), can be given safely to subjects who have failed previous transplant(s).	12 months

Collaborators and Investigators

• Sponsor: University of Arkansas
• Investigators: Principal Investigator: Mauricio Pineda-Roman, MD, University of Arkansas

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: December 18, 2007
• First Submitted That Met QC Criteria: December 18, 2007
• First Posted (Estimate): December 20, 2007

Study Record Updates

• Last Update Posted (Estimate): May 3, 2011
• Last Update Submitted That Met QC Criteria: May 2, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Multiple Myeloma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Dexamethasone; Thalidomide; Melphalan; Bortezomib
• Other Study ID Numbers: 2007-01