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

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Bortezomib 1 mg/m2; Drug: Melphalan; Drug: Bortezomib 1.3 mg/m2; Drug: Bortezomib 1.6 mg/m2

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
• Enrollment (Actual): 32
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I Cohort - Bortezomib 1 mg/m2; Bortezomib at 1 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.	Drug: Bortezomib 1 mg/m2; 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 Names: 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 Names: Alkeran
Experimental: Phase I Cohort - Bortezomib 1.3 mg/m2; Bortezomib at 1.3 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.	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 Names: Alkeran; Drug: Bortezomib 1.3 mg/m2; 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 Names: Velcade
Experimental: Phase I Cohort - Bortezomib 1.6 mg/m2; Bortezomib at 1.6 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.	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 Names: Alkeran; Drug: Bortezomib 1.6 mg/m2; 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 Names: Velcade
Experimental: Phase II Cohort; Bortezomib at 1.6 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.	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 Names: Alkeran; Drug: Bortezomib 1.6 mg/m2; 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 Names: Velcade

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Maximum Tolerated Dose of Bortezomib (MTD)	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	During dosing of Bortezomib on Day -4 to Day -1 of ASCT

Collaborators and Investigators

• Sponsor: Hackensack Meridian Health
• Investigators: Principal Investigator: Scott D Rowley, MD, Director-Blood and Marrow Transplantation Program

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: October 31, 2008
• First Submitted That Met QC Criteria: November 3, 2008
• First Posted (Estimate): November 4, 2008

Study Record Updates

• Last Update Posted (Actual): August 11, 2022
• Last Update Submitted That Met QC Criteria: July 15, 2022
• Last Verified: July 1, 2022

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; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Melphalan; Bortezomib
• Other Study ID Numbers: 06.05.109B