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Busulfan in Multiple Myeloma

Primary Purpose

Multiple Myeloma

Status

Terminated

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

Busulfan

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring cancer, myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects must have ≥ 3 x 106 CD34 cell/kg in storage for this study.
Subjects must have symptomatic multiple myeloma at their new patient consult at HCI that, in the opinion of the enrolling physician, requires treatment.
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.
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).
Subjects must demonstrate adequate cardiac function (≥40% LVEF on ECHO or MUGA).
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)
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.
Subjects must have a SWOG performance score of 0-2 unless due to myeloma-related bone pain.
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.
Female participants of child-bearing potential must have a negative pregnancy test documented within 10 days of enrollment.

Exclusion Criteria:

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)
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.
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.
Subjects must not have had a prior autologous or allogeneic bone marrow transplant.
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.
Patients who have < 3 million CD34 cells/kg stored for this protocol.

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Busulfan

Arm Description

Busulfex given to patients who are either ≥65 years or have renal insufficiency

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT00934232

First Posted

June 4, 2009

Last Updated

May 19, 2017

Sponsor

Guido Tricot

Collaborators

Otsuka Pharmaceutical Development & Commercialization, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT00934232

Brief Title

Busulfan in Multiple Myeloma

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2017

Overall Recruitment Status

Terminated

Why Stopped

PI left the institution

Study Start Date

August 2009 (Actual)

Primary Completion Date

February 2012 (Actual)

Study Completion Date

February 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Guido Tricot

Collaborators

Otsuka Pharmaceutical Development & Commercialization, Inc.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma

Keywords

cancer, myeloma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

13 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Busulfan

Arm Type

Experimental

Arm Description

Busulfex given to patients who are either ≥65 years or have renal insufficiency

Intervention Type

Drug

Intervention Name(s)

Busulfan

Other Intervention Name(s)

Busulfex ®

Intervention Description

Busulfan (Bu) is a bifunctional alkylating agent currently used almost exclusively as a component of conditioning regimens for both autologous and allogeneic stem-cell transplants.

Primary Outcome Measure Information:

Title

Time Frame

1 year

Secondary Outcome Measure Information:

Title

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.

Time Frame

18 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subjects must have ≥ 3 x 106 CD34 cell/kg in storage for this study. Subjects must have symptomatic multiple myeloma at their new patient consult at HCI that, in the opinion of the enrolling physician, requires treatment. 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. 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). Subjects must demonstrate adequate cardiac function (≥40% LVEF on ECHO or MUGA). 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) 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. Subjects must have a SWOG performance score of 0-2 unless due to myeloma-related bone pain. 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. Female participants of child-bearing potential must have a negative pregnancy test documented within 10 days of enrollment. Exclusion Criteria: 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) 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. 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. Subjects must not have had a prior autologous or allogeneic bone marrow transplant. 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. Patients who have < 3 million CD34 cells/kg stored for this protocol.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Guido Tricot, MD, PhD

Organizational Affiliation

University of Iowa

Official's Role

Principal Investigator

12. IPD Sharing Statement

Plan to Share IPD

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Busulfan in Multiple Myeloma

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