Clinical trial NCT00784823: Study Combining Bortezomib With High Dose Melphalan to Treat Multiple Myeloma
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Lead sponsor: Hackensack Meridian Health
Sponsor class: OTHER
First posted: 2008-11-04
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 76
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 3 + 3 Dose Escalation
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: The Maximum Tolerated Dose of Bortezomib (MTD)
timeFrame: During dosing of Bortezomib on Day -4 to Day -1 of ASCT
Secondary outcomes:
Other outcomes:
Locations:
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
Study officials:
affiliation: Director-Blood and Marrow Transplantation Program
name: Scott D Rowley, MD
role: PRINCIPAL_INVESTIGATOR
References: