IV Busulfan Plus Bortezomib Conditioning Regimen for Second Autologous Stem Cell Transplant in Multiple Myeloma Patients

NCT01009840 | Completed Phase 2 Results DMC

• 1 other identifier: 273-08-205
• Study Type: interventional
• Target: 30
• Locations: 2 countries
• Sites: 13

Brief Summary

Study for the outcome and safety of individualized busulfan dosing with bortezomib for patients preparing for a second stem cell transplant to treat multiple myeloma.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Bone marrow transplant; Stem cell transplant; Busulfan; Bortezomib

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Overall Disease Response at Month 6

  The percentage of participants reported in each disease category by International Myeloma Working Group (IMWG) uniform response criteria for Multiple Myeloma 6 months after autologous Hematopoietic stem cell transplant. Overall Disease Response categories were: \[stringent Complete Response (sCR)=CR + normal Free Light Chain (FLC) ratio + absence of clonal cells in bone marrow\], \[Complete Response (CR)=Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow\], \[Very Good Partial Response (VGPR)=Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein + urine M-protein level \<100 mg/24 hour\], \[Partial Response (PR)=≥50% reduction of serum M-protein and reduction in 24 hour urine M-protein by ≥90% or to \<200 mg per 24 hour\], \[Stable Disease (SD)=Not meeting criteria for CR, VGPR, PR or progressive disease\] or \[Progressive Disease (PD)\].

  6 Months

Secondary Outcomes (9)

• Overall Survival

  6 Months

• Percentage of Participants With Overall Survival Events

  6 Months

• Progression-free Survival

  6 Months

• Percentage of Participants With Progression-free Survival Events

  6 Months

• Percent Change in IV Busulfan Dose

  Baseline (Day -12 to -9), Day -5

Study Arms (1)

IV busulfan

EXPERIMENTAL

Intravenous (IV) busulfan was administered as a single daily 3-hour continuous infusion based on the PK-directed dose recommendation for 4 days beginning on Day -5 followed by a single bortezomib 1.3 mg/m\^2 dose administered as a 3 to 5-second bolus IV injection on Day -1 prior to HSCT.

Drug: IV busulfan; Drug: bortezomib; Procedure: Autologous Hematopoietic Stem Cell Transplant (HSCT)

Interventions

IV busulfan DRUG

PK-directed dosing of IV busulfan for 4 days

Also known as: Busulfex®

IV busulfan

bortezomib DRUG

Single IV bortezomib at a dose of 1.3 mg/m\^2.

Also known as: Velcade®

IV busulfan

Autologous Hematopoietic Stem Cell Transplant (HSCT) PROCEDURE

IV busulfan

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 75 years, inclusive.
• Subjects must have multiple myeloma which requires treatment for relapsed disease and are eligible for the planned autologous HSCT.
• Subjects must have had one previous autologous HSCT, at least one year prior to the planned autologous HSCT in this study.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
• Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test in all women of child-bearing potential.
• Subjects who are surgically sterile (ie, have undergone orchidectomy or hysterectomy); female subjects who have been postmenopausal for at least 12 consecutive months; or subjects who agree to remain abstinent or to practice double-barrier forms of birth control from trial screening through 30 days (for females) and 90 days (for males) from the last dose of the investigational medicinal product (IMP). If employing birth control, two of the following precautions must be used: vasectomy, tubal ligation, vaginal diaphragm, intrauterine device (IUD), birth control pill, birth control implant, condom, or sponge with spermicide.
• Subjects in whom the minimum stem cell dose of 2.0 x 10\^6 cluster of differentiation 34 (CD34)+ cells/kg has been collected.
• Ability to provide written informed consent prior to initiation of any study-related procedures, and ability, in the opinion of the Principal Investigator, to comply with all requirements of the study.

You may not qualify if:

• Prior treatment history of allogeneic HSCT for any medical reason, not limited to myeloma treatment.
• Prior treatment history of more than one autologous HSCT or high-dose chemotherapy with stem cell rescue for any medical reason, not limited to myeloma treatment.
• Prior treatment with busulfan or gemtuzumab ozogamicin for any reason.
• Presence of a t(4;14) or p53 gene deletion as determined by fluorescence in situ hybridization (FISH) during the screening process or documented t(4; 14) or p53 gene deletion obtained during a time of active disease by any method.
• Systemic amyloidosis.
• Known allergy to boron or any components of bortezomib.
• Left ventricular ejection fraction (LVEF) \< 45% as measured by either multi-gated acquisition scan (MUGA) or echocardiogram (ECHO) performed within 75 days prior to day of busulfan test dose. If cyclophosphamide was used for stem cell harvest, an ECHO or MUGA must be done prior to enrollment to confirm adequate cardiac function.
• Uncontrolled arrhythmia or symptomatic cardiac disease at the time of screening.
• Symptomatic pulmonary disease, based on Forced Expiratory Volume in 1 Second (FEV1), Forced Vital Capacity (FVC) or Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) \< 50% of predicted (corrected for hemoglobin) measured within 75 days prior to day of busulfan test dose.
• Aspartate transaminase (AST)/alanine transaminase (ALT) ≥ 3 x the upper limit of normal (ULN),
• History of elevated total serum bilirubin \>2 mg/dL that had been caused by previous chemotherapy at any point, or total bilirubin \> 2.0 mg/dL at the time of screening with the exception of Gilbert's disease.
• Hepatic synthetic dysfunction evident International Normalized Ratio (INR) ≥ 2.0 at the time of screening.
• Any previous history of fulminant liver failure, cirrhosis, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, and symptomatic biliary disease.
• Prior total body irradiation therapy or radiation therapy directly applied to the liver.
• Known history of or current hepatitis B, hepatitis C, HIV, or uncontrolled active infection of any kind at the time of test dose. If serology antibody studies are positive, a quantitative polymerase chain reaction (PCR) must be completed to confirm lack of active infection.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (13)

Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, 30342, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

University of Maryland School of Medicine - Marlene & Stewart Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

University of Pennsylvania -Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

The Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, 15224, United States

Location

South Texas Veterans Health Care System

San Antonio, Texas, 78229, United States

Location

Texas Transplant Physician Group, PLLC

San Antonio, Texas, 78229, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Busulfan; Bortezomib

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)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Global Medical Affairs
• Organization: Otsuka Pharmaceutical Development and Commercialization

800 562-3974

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2009
• First Posted: November 9, 2009
• Study Start: May 1, 2010
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: September 25, 2014
• Results First Posted: August 7, 2014

Record last verified: 2014-09

Locations

CA (2); US (11)