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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

Phase 2
18 Years
75 Years
Not Enrolling
Multiple Myeloma

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Trial Information

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

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 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.

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 106 CD34+ cells/kg has been

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

14. Prior total body irradiation therapy or radiation therapy directly applied to the

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 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine overall response rate (ORR) as measured by myeloma assessments including serum and 24 hour urine measurements, skeletal surveys and bone marrow aspiration or biopsy

Outcome Time Frame:

Six Months

Safety Issue:



United States: Food and Drug Administration

Study ID:




Start Date:

May 2010

Completion Date:

March 2012

Related Keywords:

  • Multiple Myeloma
  • Multiple Myeloma
  • Bone marrow transplant
  • Stem cell transplant
  • Busulfan
  • Bortezomib
  • Multiple Myeloma
  • Neoplasms, Plasma Cell



Arizona Cancer CenterTucson, Arizona  85724
Loyola University Medical CenterMaywood, Illinois  60153
Huntsman Cancer InstituteSalt Lake City, Utah  84112
Indiana University Melvin and Bren Simon Cancer CenterIndianapolis, Indiana  46202-5289
Blood and Marrow Transplant Group of GeorgiaAtlanta, Georgia  30342-1601
The Western Pennsylvania HospitalPittsburgh, Pennsylvania  15224
Karmanos Cancer InstituteDetroit, Michigan  48201
South Texas Veterans Health Care SystemSan Antonio, Texas  78229
Texas Transplant Physician Group, PLLCSan Antonio, Texas  78229
University of Maryland School of Medicine - Marlene & Stewart Greenebaum Cancer CenterBaltimore, Maryland  21201
University of Pennsylvania -Abramson Cancer CenterPhiladelphia, Pennsylvania  19104