Study Combining Bortezomib With High Dose Melphalan to Treat Multiple Myeloma

Phase 1

Completed

• Conditions: Multiple Myeloma
• Interventions: Drug: Bortezomib 1.6 mg/m2; Drug: Bortezomib 1 mg/m2; Drug: Bortezomib 1.3 mg/m2; Drug: Melphalan

• Registration Number: NCT00784823
• Lead Sponsor: Hackensack Meridian Health

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.

Study Timeline

• Study Start: 2007-01
• Study First Submitted: 2008-10-31
• Study First Submitted QC: 2008-11-03
• Study First Posted: 2008-11-04
• Primary Completion: 2013-12
• Study Completion: 2013-12
• Results First Submitted: 2021-02-25
• Status Verified: 2022-07
• Results First Submitted QC: 2022-07-15
• Last Update Submitted: 2022-07-15
• Results First Posted: 2022-08-11
• Last Update Posted: 2022-08-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase II 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.
Phase I Cohort - Bortezomib 1 mg/m2	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.
Phase I Cohort - Bortezomib 1.3 mg/m2	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.
Phase I Cohort - Bortezomib 1.6 mg/m2	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.
Phase I Cohort - Bortezomib 1 mg/m2	Melphalan	Bortezomib at 1 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
Phase I Cohort - Bortezomib 1.6 mg/m2	Melphalan	Bortezomib at 1.6 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
Phase I Cohort - Bortezomib 1.3 mg/m2	Melphalan	Bortezomib at 1.3 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.
Phase II Cohort	Melphalan	Bortezomib at 1.6 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.

Primary Outcome Measures

Name	Time	Method
The Maximum Tolerated Dose of Bortezomib (MTD)	During dosing of Bortezomib on Day -4 to Day -1 of ASCT	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

Trial Locations

Locations (1)

Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States