IV Busulfan Plus Bortezomib Conditioning Regimen for Second Autologous Stem Cell Transplant in Multiple Myeloma Patients
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: IV busulfan; bortezomib; Autologous Hematopoietic Stem Cell Transplant (HSCT)
Intervention description: PK-directed dosing of IV busulfan for 4 days; Single IV bortezomib at a dose of 1.3 mg/m^2.
Intervention MeSH terms: Bortezomib; Busulfan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Multiple Myeloma; Bone marrow transplant; Stem cell transplant; Busulfan; Bortezomib

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age 18 to 75 years, inclusive.

          2. Subjects must have multiple myeloma which requires treatment for relapsed disease and
             are eligible for the planned autologous HSCT.

          3. Subjects must have had one previous autologous HSCT, at least one year prior to the
             planned autologous HSCT in this study.

          4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.

          5. Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test in all women of
             child-bearing potential.

          6. 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.

          7. Subjects in whom the minimum stem cell dose of 2.0 x 10^6 cluster of differentiation
             34 (CD34)+ cells/kg has been collected.

          8. 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.

        Exclusion Criteria:

          1. Prior treatment history of allogeneic HSCT for any medical reason, not limited to
             myeloma treatment.

          2. 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.

          3. Prior treatment with busulfan or gemtuzumab ozogamicin for any reason.

          4. 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.

          5. Systemic amyloidosis.

          6. Known allergy to boron or any components of bortezomib.

          7. 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.

          8. Uncontrolled arrhythmia or symptomatic cardiac disease at the time of screening.

          9. 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.

         10. Aspartate transaminase (AST)/alanine transaminase (ALT) ≥ 3 x the upper limit of
             normal (ULN),

         11. 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.

         12. Hepatic synthetic dysfunction evident International Normalized Ratio (INR) ≥ 2.0 at
             the time of screening.

         13. 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.

         14. Prior total body irradiation therapy or radiation therapy directly applied to the
             liver.

         15. 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.

         16. Serum creatinine >2.0 mg/dL at the time of Screening.

         17. ≥ Grade 1 neuropathy with pain, or > Grade 2 neuropathy without pain (subjects with
             neuropathy caused by a previous regimen that is recovered to ≤ Grade 2 and stable
             without pain may be included).

         18. Women who are pregnant or lactating.

         19. Current or history of drug and/or alcohol abuse.

         20. Use of other investigational therapies within 30 days