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
Overview
- Phase
- Phase 1
- Intervention
- Bortezomib 1 mg/m2
- Conditions
- Multiple Myeloma
- Sponsor
- Hackensack Meridian Health
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- The Maximum Tolerated Dose of Bortezomib (MTD)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •A confirmed diagnosis of multiple myeloma
- •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
- •Age:18yrs-76yrs at time of melphalan administration
- •Gender: There is no gender restriction
- •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
- •Recovery from complications of salvage therapy, if administered -
Exclusion Criteria
- •Diagnosis other than multiple myeloma
- •Chemotherapy or radiotherapy within 28 days of initiating treatment in this study
- •Prior dose-intense therapy within 56 days of initiating treatment in this study
- •Uncontrolled bacterial,viral,fungal or parasitic infections
- •Uncontrolled CNS metastases
- •Known amyloid deposition in heart
- •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
Arms & Interventions
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.
Intervention: Bortezomib 1 mg/m2
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.
Intervention: Melphalan
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.
Intervention: Bortezomib 1.3 mg/m2
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.
Intervention: Melphalan
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.
Intervention: Bortezomib 1.6 mg/m2
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.
Intervention: Melphalan
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.
Intervention: Bortezomib 1.6 mg/m2
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.
Intervention: Melphalan
Outcomes
Primary Outcomes
The Maximum Tolerated Dose of Bortezomib (MTD)
Time Frame: 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