Study Combining Bortezomib With High Dose Melphalan to Treat Multiple Myeloma

NCT ID: NCT00784823

Last Updated: 2022-08-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2013-12-31

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.

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Bortezomib 1 mg/m2

Intervention Type: DRUG

• 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

Melphalan

Intervention Type: DRUG

• 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

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.

Group Type: EXPERIMENTAL

Bortezomib 1.3 mg/m2

Intervention Type: DRUG

• 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

Melphalan

Intervention Type: DRUG

• 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

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.

Group Type: EXPERIMENTAL

Bortezomib 1.6 mg/m2

Intervention Type: DRUG

• 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

Melphalan

Intervention Type: DRUG

• 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

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.

Group Type: EXPERIMENTAL

Bortezomib 1.6 mg/m2

Intervention Type: DRUG

• 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

Melphalan

Intervention Type: DRUG

• 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

Interventions

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

Intervention Type: 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

Intervention Type: 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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Velcade; Velcade; Velcade; Alkeran

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 76 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hackensack Meridian Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Scott D Rowley, MD

Role: PRINCIPAL_INVESTIGATOR

Director-Blood and Marrow Transplantation Program

Locations

Hackensack University Medical Center

Hackensack, New Jersey, United States

Countries

United States

Other Identifiers

06.05.109B

Identifier Type: -

Identifier Source: org_study_id