Study Combining Bortezomib With High Dose Melphalan to Treat Multiple Myeloma

NCT00784823 | Completed Phase 1 Results DMC

• 1 other identifier: 06.05.109B
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• The Maximum Tolerated Dose of Bortezomib (MTD)

  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

  During dosing of Bortezomib on Day -4 to Day -1 of ASCT

Study Arms (4)

Phase I Cohort - Bortezomib 1 mg/m2

EXPERIMENTAL

Bortezomib at 1 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.

Drug: Bortezomib 1 mg/m2; Drug: Melphalan

Phase I Cohort - Bortezomib 1.3 mg/m2

EXPERIMENTAL

Bortezomib at 1.3 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.

Drug: Bortezomib 1.3 mg/m2; Drug: Melphalan

Phase I Cohort - Bortezomib 1.6 mg/m2

EXPERIMENTAL

Bortezomib at 1.6 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.

Drug: Bortezomib 1.6 mg/m2; Drug: Melphalan

Phase II Cohort

EXPERIMENTAL

Bortezomib at 1.6 mg/m2 on days -4 and -1 before transplantation with melphalan 200 mg/m2 given on day -2.

Drug: Bortezomib 1.6 mg/m2; Drug: Melphalan

Interventions

Bortezomib 1 mg/m2 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

Also known as: Velcade

Phase I Cohort - Bortezomib 1 mg/m2

Bortezomib 1.3 mg/m2 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

Also known as: Velcade

Phase I Cohort - Bortezomib 1.3 mg/m2

Bortezomib 1.6 mg/m2 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

Also known as: Velcade

Phase I Cohort - Bortezomib 1.6 mg/m2; Phase II Cohort

Melphalan 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

Also known as: Alkeran

Phase I Cohort - Bortezomib 1 mg/m2; Phase I Cohort - Bortezomib 1.3 mg/m2; Phase I Cohort - Bortezomib 1.6 mg/m2; Phase II Cohort

Eligibility Criteria

• Age: 18 Years - 76 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 -

You may not qualify if:

• 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)

Sponsors & Collaborators

• Hackensack Meridian Health: lead

Study Sites (1)

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Melphalan

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Limitations and Caveats

The limited number of patients limited our ability to analyze groups separately for adverse event reporting. As a result, adverse events were collected irrespective of dose and therefore cannot be separated further.

Results Point of Contact

• Title: Joshua Zenreich
• Organization: Hackensack Meridian Health

Joshua.Zenreich@hmhn.org

551-996-4248

Study Officials

• Scott D Rowley, MD

  Director-Blood and Marrow Transplantation Program

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 3 + 3 Dose Escalation

Study Record Dates

• First Submitted: October 31, 2008
• First Posted: November 4, 2008
• Study Start: January 1, 2007
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: August 11, 2022
• Results First Posted: August 11, 2022

Record last verified: 2022-07

Locations

US (1)