Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Antineoplastic Agents

All Drugs and Chemicals

Bortezomib

Busulfan

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

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.

PK-directed dosing of IV busulfan for 4 days

IV busulfan

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

bortezomib

Autologous Hematopoietic Stem Cell Transplant (HSCT)

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.

Evaluation of six-month response in relapsed multiple myeloma subjects, who have had a prior autologous HSCT (greater than one year previously) receiving an IV busulfan-based conditioning regimen with the combination of pharmacokinetic (PK)-guided IV busulfan dosing and bortezomib, followed by a second autologous HSCT.

Assessment of the safety profile of this conditioning regimen will also be completed.

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

A Phase 2a Study of Once Daily Intravenous Busulfan With Bortezomib, Followed by an Autologous Hematopoietic Stem Cell Transplant (HSCT) in Subjects With Relapsed Multiple Myeloma After Prior Autologous HSCT

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 \[Progressive Disease (PD)\].

Overall Survival was defined as the time in days from transplantation to death due to all causes.

Progression-free Survival (PFS) defined as the time from transplantation to the occurrence of the event that was death or first recurrence of progressive disease (PD) by IMWG criteria. PD was defined as an Increase of ≥25% from the lowest response value in any one or more of the following: 1)Serum M-component and/or (the absolute increase must be ≥0.5 g/dL), 2)Urine M-component and/or (the absolute increase must be ≥200 mg/24 hr), 3)In patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be \>10 mg/dL, 4)Bone marrow plasma cell percentage; the absolute percentage must be ≥10%, 5)Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas and/or 6)Development of hypercalcaemia that can be attributed solely to the plasma cell proliferative diso

Progression-free survival events are death or first recurrence of progressive disease by International Myeloma Working Group Criteria.

The percent change in dose is relative to the busulfan dose administered at the Baseline Visit (Day -12 to -9) when a dose of 0.8 mg/kg was administered and on Day -5 when the Seattle Cancer Care Alliance recommended PK-adjusted dose was administered.

A test dose of IV busulfan 0.8 mg/kg was infused at Baseline (Day -12 to -9) to verify a target busulfan integrated AUC of 20,000 μM\*min with a range of 16,000 to 24,000. If necessary the dose could be adjusted. The PK-directed dose recommendation based on the test dose was administered at Day -5. Blood samples for PK analysis were collected at 0, 15, 30 minutes after the End of Infusion and 240, 300, 360 minutes after start of the infusion. Gas chromatography with mass selective detection (GC-MS) was used to determine the busulfan level in plasma. The ratio was calculated: AUC/Target AUC.

A test dose of IV busulfan 0.8 mg/kg was infused at Baseline (Day -12 to -9) to verify a target busulfan integrated AUC of 20,000 μM\*min with a range of 16,000 to 24,000. If necessary the dose could be adjusted. The PK-directed dose recommendation based on the test dose was administered at Day -5. Blood samples for PK analysis were collected at 0, 15, 30 minutes after the End of Infusion and 240, 300, 360 minutes after start of the infusion. GC-MS was used to determine the busulfan level in plasma. The percent difference was calculated between AUC and the Target AUC.

The percentage of participants with death related to transplant.

The Baltimore criteria for veno-occlusive disease was defined as the development of hyperbilirubinemia with serum bilirubin \> 2 mg/dl within 21 days after transplantation and at least 2 of the following clinical signs and symptoms: (1) hepatomegaly, usually painful, (2) \> 5% weight gain, or (3) ascites.

Otsuka Pharmaceutical Development & Commercialization, Inc.

IV Busulfan

Age, Continuous

Sex: Female, Male

Global Medical Affairs

sCR or CR or VGPR

PR or SD or PD

Not Assessed

Intent-to-treat population included all participants who received the PK-directed IV busulfan followed by autologous HSCT.

Percentage of Participants With Overall Disease Response at Month 6

Overall Survival

Percentage of Participants With Overall Survival Events

Progression-free Survival

Percentage of Participants With Progression-free Survival Events

Percent Change in IV Busulfan Dose

Ratio Area Under Curve (AUC)/Target AUC

Percent Difference Between Area Under Curve (AUC) and Target AUC

Safety population included all participants who received IV busulfan.

Percentage of Participants With Transplant-Related Mortality

Percentage of Participants With Hepatic Veno-Occlusive Disease Based on Baltimore Criteria

Intravenous (IV) busulfan was administered as a single daily 3-hour continuous infusion based on the pharmacokinetic (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 hematopoietic stem cell transplant (HSCT).

Spots Global Cancer Trial Database for IV Busulfan Plus Bortezomib Conditioning Regimen for Second Autologous Stem Cell Transplant in Multiple Myeloma Patients

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial