Study Combining Bortezomib With High Dose Melphalan to Treat Multiple Myeloma (Mel-Vel)

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. Identifier: NCT00784823
Recruitment Status : Completed
First Posted : November 4, 2008
Last Update Posted : February 4, 2014
Information provided by (Responsible Party):
Hackensack University Medical Center

Brief Summary:
The purpose of this study is to determine the tolerance and potential efficacy of combining dose intense melphalan with escalating doses of bortezomib in patients with multiple myeloma undergoing autologous stem cell transplantation.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Bortezomib Drug: Melphalan Phase 1 Phase 2

Detailed Description:
Multiple myeloma is the second most common hematological malignancy that has affected approximately 40,000 Americans.Conventional chemotherapy has achieved limited control of this disease but studies have reported improved response rates for patients who are treated with dose-intense therapy and autologous hematopoietic stem cell transplantation. This Phase I/II study will investigate the potential of combination therapy of dose-intense melphalan with escalating doses of bortezomib.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Escalating Doses of Bortezomib in Conjunction With High Dose Melphalan as a Conditioning Regimen for Autologous Peripheral Blood Stem Cell Transplantation in Patients With Multiple Myeloma
Study Start Date : January 2007
Primary Completion Date : December 2013
Study Completion Date : December 2013

Arm Intervention/treatment
Experimental: Combined dose intense Melphalan with bortezomib (MTD)

The purpose of this study is to determine the tolerance and potential efficacy of combining dose intense melphalan with escalating doses of bortezomib in patients with multiple myeloma undergoing autologous stem cell transplantation.

Combined dose intense Melphalan with maximum tolerated dose of bortezomib (MTD)

Drug: Bortezomib
  • Bortezomib is administered by rapid I.V. push (over 3-5 seconds) via a central or peripheral vein into a flowing saline line
  • Bortezomib will be administered any time on day -4 and 24 hrs after the start of the melphalan infusion on day -1
  • Dosing will be based on actual body weight Patient weight must be measured within seven days of the start of the treatment regimen
Other Name: Velcade
Drug: Melphalan
  • Melphalan is administered by rapid intravenous infusion via a central or peripheral vein over one hour
  • Melphalan will be dissolved with 10 ml of diluent to a concentration of 5 mg/mL which is then immediately diluted in 0.9% normal saline to a concentration NOT exceeding 0.45 mg/mL prior to administration
  • The final dilution of melphalan is physically and chemically stable for 60 minutes and therefore will be administered within that time period
  • Melphalan will be given as a single dose (not split over 2 or more days)
  • Dosing will be based body surface area calculated using actual body weight
Other Name: Alkeran

Primary Outcome Measures :
  1. Maximum Tolerated Dose The maximum tolerated dose of bortezomib (MTD) will be defined as the dose level prior to that resulting in two out of six patients experiencing a DLT [ Time Frame: 3 years ]

Information from the National Library of Medicine

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 76 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. A confirmed diagnosis of multiple myeloma
  2. Show progression of disease after a previous cycle of dose-intense melphalan, or less than 25% decrease in paraprotein measured at 8 weeks after a prior cycle of dose-intense melphalan

    • May have received intervening therapies for disease progression after dose-intense melphalan and enrollment in this protocol
  3. Age:18yrs-76yrs at time of melphalan administration
  4. Gender: There is no gender restriction
  5. Availability of >2x10^6 autologous peripheral blood CD34+ cells/kg or a syngeneic donor meeting eligibility criteria for syngeneic donation

    • Syngeneic transplantation is preferred
    • For patients enrolled in the phase I part of this study, >1x10^6 autologous or syngeneic peripheral blood CD34+ cells/kg remaining in storage as "backup" in case of engraftment failure
  6. Recovery from complications of salvage therapy, if administered -

Exclusion Criteria:

  1. Diagnosis other than multiple myeloma
  2. Chemotherapy or radiotherapy within 28 days of initiating treatment in this study
  3. Prior dose-intense therapy within 56 days of initiating treatment in this study
  4. Uncontrolled bacterial,viral,fungal or parasitic infections
  5. Uncontrolled CNS metastases
  6. Known amyloid deposition in heart
  7. Organ dysfunction

    • LVEF<40% or cardiac failure not responsive to therapy
    • FVC,FEV1,or DLCO<50% of predicted and/or receiving supplementary continuous oxygen
    • Evidence of hepatic synthetic dysfunction, or total bilirubin>2x or AST>3x ULN
    • Measured creatinine clearance <20ml/min
    • Sensory peripheral neuropathy grade 4
  8. Karnofsky score<70% unless a result of bone disease directly caused by myeloma
  9. Life expectancy limited by another co-morbid illness
  10. History of another malignancy in remission <2yrs (other than basal cell carcinoma)
  11. Pregnant (women)or unwilling to use acceptable birth control methods (men or women) for twelve months after treatment
  12. Documented hypersensitivity to melphalan or bortezomib or any components of the formulation
  13. Patients unable or unwilling to provide consent

Information from the National Library of Medicine

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 identifier (NCT number): NCT00784823

United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
Sponsors and Collaborators
Hackensack University Medical Center
Principal Investigator: Scott D Rowley, MD Director-Blood and Marrow Transplantation Program

Responsible Party: Hackensack University Medical Center Identifier: NCT00784823     History of Changes
Other Study ID Numbers: 06.05.109B
First Posted: November 4, 2008    Key Record Dates
Last Update Posted: February 4, 2014
Last Verified: February 2014

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs