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A Phase I/II Open Label Study of IV Busulfan (Busulfex®) in Multiple Myeloma Patients 65 Years of Age or Older, or With Renal Insufficiency Undergoing Autologous Transplantation


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Multiple Myeloma

Thank you

Trial Information

A Phase I/II Open Label Study of IV Busulfan (Busulfex®) in Multiple Myeloma Patients 65 Years of Age or Older, or With Renal Insufficiency Undergoing Autologous Transplantation


This study is for first line treatment for multiple myeloma patients in patients >65 years
or have renal insufficiency Busulfan introduces cytopenia much slower than melphalan while
the time to recover after transplantation is the same. The duration of cytopenia with
busulfan should therefore be shorter. Busulfan given in myeloma patients with renal failure
has proven to be effective.

The initial proposed dose level in our study will be 3.2mg/kg of body weight over 6 hours
for 3 days. The next levels will be 3.2mg/kg of body weight over 6 hours for 4 days, 4.3
mg/kg of body weight over 6 hours for 3 days, 5.6 mg/kg of body weight over 6 hours for 2
days, and 6.4 mg/kg of body weight over 6 hours for 2 days. Three patients per group will
be entered at the first level. Further enrollment will be dependent upon toxicities
observed. All dose escalations will be initiated after the PI has reviewed the toxicity data
available on the prior dose levels and confirms that it is safe to proceed to subsequent
dose level(s). Maximum tolerated dose will defined as the dose level immediately below the
dose level at which ≥ 2 of 6 patients experiences a grade 4 non-hematological toxicity that
is unexpected, related, and serious, and it will be evaluated separately for patients > 65
years of age or in patients with renal insufficiency.


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.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

determine MTD of Busulfex given safely over least number of days patients who are either ≥65 years Group 1) or have renal insufficiency (Group 2), defined as creatinine >3mg/dL or creatinine clearance <30 mL/min.

Outcome Time Frame:

1 year

Safety Issue:

Yes

Principal Investigator

Guido Tricot, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Utah

Authority:

United States: Institutional Review Board

Study ID:

32857

NCT ID:

NCT00934232

Start Date:

August 2009

Completion Date:

August 2012

Related Keywords:

  • Multiple Myeloma
  • cancer
  • myeloma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell

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