Overview

Busulfan in Multiple Myeloma

Status:
Terminated
Trial end date:
2012-02-01
Target enrollment:
0
Participant gender:
All
Summary
Two main objectives of the study are: Primary: To determine the MTD of Busulfex ® that can be given safely over the least number of days to myeloma patients who are either ≥65 years of age (Group 1) or have renal insufficiency (Group 2), defined as creatinine >3mg/dL or creatinine clearance <30 mL/min. Secondary: To perform pharmacokinetic (PK) studies to evaluate individual variability and the relationship to toxicities in each of the two groups at each proposed dose level.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Guido Tricot
Collaborator:
Otsuka Pharmaceutical Development & Commercialization, Inc.
Treatments:
Busulfan
Criteria
Inclusion Criteria:

1. Subjects must have ≥ 3 x 106 CD34 cell/kg in storage for this study.

2. Subjects must have symptomatic multiple myeloma at their new patient consult at HCI
that, in the opinion of the enrolling physician, requires treatment.

3. Subjects must be at least 65 years of age and/or diagnosed with renal insufficiency,
defined as serum creatinine ≥3mg/dL or a creatinine clearance of less than
30mL/minute.

4. Subjects must not have a history of chronic obstructive or chronic restrictive
pulmonary disease. Subjects must demonstrate adequate pulmonary function studies
defined as ≥50% of predicted on mechanical aspects (FEV1, FVC) and diffusion capacity
(DLCO).

5. Subjects must demonstrate adequate cardiac function (≥40% LVEF on ECHO or MUGA).

6. Subjects must demonstrate adequate liver functions with total bilirubin and
transaminase levels no higher than 1.5 times the institutional upper limit of normal.
(If total bilirubin is > 1.5 times the upper limit of normal, a direct bilirubin needs
to be assessed. Subject eligible as long as the direct bilirubin is not > 1.5 times
the upper limit of normal)

7. Subjects must have at least one evaluable myeloma marker by which to judge response:
serum M protein >1g/dL, free light chains in the serum that more than four times the
upper limit of normal, urine M protein of ≥ 500 mg, urine free light chains of ≥ 500
mg/day, bone marrow plasmacytosis with >20% plasma cells, extramedullary
plasmacytosis, or MRI/FDG-PET/CT scan demonstrating 1 or more focal lesions due to
myeloma.

8. Subjects must have a SWOG performance score of 0-2 unless due to myeloma-related bone
pain.

9. Subjects must be informed of the investigational nature of the study and must sign an
IRB-approved informed consent in accordance with institutional and federal guidelines.

10. Female participants of child-bearing potential must have a negative pregnancy test
documented within 10 days of enrollment.

Exclusion Criteria:

1. Subjects must not have serum transaminases >1.5 times the upper limit of normal and/or
a direct bilirubin >1.5 time the institutional upper limit of normal (direct bilirubin
to be assessed only if the total bilirubin is > 1.5 times the upper limit of normal)

2. Subjects must not be HIV positive or have active Hepatitis B or Hepatitis C infection.
If serology antibody studies are positive, a quantitative PCR must be done to confirm.

3. Subjects must not have a prior malignancy in which life expectancy, which in the
opinion of the investigator, is more likely to be determined by the prior malignancy
than the myeloma. Patients must not be currently receiving therapy for the prior
malignancy.

4. Subjects must not have had a prior autologous or allogeneic bone marrow transplant.

5. Subjects must not be pregnant or nursing. Women and men of reproductive potential may
not participate unless they agree to use an effective contraceptive method.

6. Patients who have < 3 million CD34 cells/kg stored for this protocol.