Study Combining Bortezomib With High Dose Melphalan to Treat Multiple Myeloma - Full Text View

Sponsored by:	Hackensack University Medical Center
Information provided by:	Hackensack University Medical Center
ClinicalTrials.gov Identifier:	NCT00784823

Purpose

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.

Condition	Intervention	Phase
Multiple Myeloma	Drug: Bortezomib Drug: Melphalan	Phase I Phase II

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Multiple Myeloma

Drug Information available for: Melphalan Bortezomib Melphalan hydrochloride Sarcolysin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Dose Comparison, Parallel Assignment, Safety/Efficacy Study
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

Further study details as provided by Hackensack University Medical Center:

Primary Outcome Measures:

Maximum Tolerated Dose 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 [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	24
Study Start Date:	January 2007
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Intervention Details:

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 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

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

Ages Eligible for Study:	18 Years to 76 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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
- Measured creatinine clearance <20ml/min
- Sensory peripheral neuropathy grade 4
Karnofsky score<70% unless a result of bone disease directly caused by myeloma
Life expectancy limited by another co-morbid illness
History of another malignancy in remission <2yrs (other than basal cell carcinoma)
Pregnant (women)or unwilling to use acceptable birth control methods (men or women) for twelve months after treatment
Documented hypersensitivity to melphalan or bortezomib or any components of the formulation
Patients unable or unwilling to provide consent

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00784823

Contacts

Contact: Marie DelFavero, RN	201-996-5834	mdelfavero@humed.com
Contact: Janet Specia, RN	201-996-5834	jspecia@humed.com

Locations

United States, New Jersey
Hackensack University Medical Center	Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Marie Del Favero, RN 201-996-5843 ext 5843 mdelfavero@humed.com
Principal Investigator: Scott D Rowley, MD, FACP
Principal Investigator: David S Siegel, MD, Ph.d
Sub-Investigator: Michele Donato, MD
Sub-Investigator: Tatiana Feldman, MD
Sub-Investigator: Stuart Goldberg, MD
Sub-Investigator: Andre Goy, MD
Sub-Investigator: Thea Friedman, Ph.D
Sub-Investigator: Robert Korngold, Ph.D

Sponsors and Collaborators

Hackensack University Medical Center

Investigators

Principal Investigator:

Scott D Rowley, MD

Director-Blood and Marrow Transplantation Program

More Information

Responsible Party:	The Cancer Center at Hackensack University Medical Center ( Scott Rowley MD )
Study ID Numbers:	06.05.109B
Study First Received:	October 31, 2008
Last Updated:	November 3, 2008
ClinicalTrials.gov Identifier:	NCT00784823
Health Authority:	United States: Institutional Review Board

Study placed in the following topic categories:

Melphalan
Immunoproliferative Disorders
Blood Protein Disorders
Hematologic Diseases
Blood Coagulation Disorders
Bortezomib
Vascular Diseases

Paraproteinemias
Hemostatic Disorders
Multiple Myeloma
Hemorrhagic Disorders
Multiple myeloma
Lymphoproliferative Disorders
Neoplasms, Plasma Cell

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Immunosuppressive Agents

Pharmacologic Actions
Protease Inhibitors
Neoplasms
Therapeutic Uses
Myeloablative Agonists
Cardiovascular Diseases
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009