UARK 2003-25: A Study of Intravenous (IV) Busulfan (Busulfex®) in Multiple Myeloma Patients - Full Text View

Purpose

The purpose of this study is to find out if patients with high risk disease because of age or kidney status can be treated more safely with a drug called Busulfex® followed by autologous transplant compared to treatment with the standard drug called melphalan, which has been shown to be quite difficult to tolerate in patients with poor kidney function and patients over the age of 65 when given in high doses.

Condition	Intervention	Phase
Multiple Myeloma	Drug: Busulfan Other: Usual care	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	UARK 2003-25: A Phase I/II Open Label Study of IV Busulfan (Busulfex®) in Multiple Myeloma Patients Older Than 65 Years of Age or With Renal Insufficiency

Resource links provided by NLM:

MedlinePlus related topics: Multiple Myeloma

Drug Information available for: Busulfan

U.S. FDA Resources

Further study details as provided by University of Arkansas:

Primary Outcome Measures:

Maximal Dose of Busulfex® Given in a 2, 3, or 4 Day Period With Acceptable Toxicity to Myeloma Patients [ Time Frame: three years ] [ Designated as safety issue: Yes ]
maximal dose of Busulfex® that can be given in a two, three, or four day period with acceptable toxicity to myeloma patients, who either are > or = 65 years of age or have renal insufficiency, defined as creatinine > 3g/dL or creatinine clearance < 30 ml/min

Secondary Outcome Measures:

Response Rate (CR, NCR) and Overall Survival of Patients on Busulfex Treatment [ Time Frame: three years ] [ Designated as safety issue: No ]
Response rate (CR, NCR) and overall survival of patients on Busulfex treatment compared to patients with similar characteristics on other regimens.

Enrollment:	14
Study Start Date:	June 2004
Study Completion Date:	October 2009
Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Busulfan study-specific treatment: Busulfex according to study design: Level I 3.2 mg/kg over 6 hours x 2 days Level II 3.2 mg/kg over 6 hours x 3 days Level III 3.2 mg/kg over 6 hours x 4 days Level IV 4.3 mg/kg over 6 hours x 3 days Level V 5.6 mg/kg over 6 hours x 2 days Level VI 6.4 mg/kg over 6 hours x 2 days	Drug: Busulfan Dexamethasone 40 mg PO 1-4 Thalidomide 200 mg PO 1-6 Cisplatin* 10 mg/m, Continuous infusion 1-4 Adriamycin** 10 mg/m2, Continuous infusion 1-4 Cyclophosphamide 400 mg/2, Continuous infusion 1-4 Etoposide 40 mg/m2, Continuous infusion 1-4 All doses will be based on calculated body weight (actual weight + ideal body weight ÷ 2) and height, and not to exceed a BSA of 2.0 m2 The daily dose of cyclophosphamide, etoposide, and cisplatin will be mixed in a 1L bag of NS to be UAMS infused over 24 hours. Adriamycin will be mixed in at least 50cc D5W to be infused over 24 hours Other Name: Busulfex
No Intervention: Usual care	Other: Usual care no intervention

Arms

Assigned Interventions

Experimental: Busulfan

study-specific treatment: Busulfex according to study design: Level I 3.2 mg/kg over 6 hours x 2 days Level II 3.2 mg/kg over 6 hours x 3 days Level III 3.2 mg/kg over 6 hours x 4 days Level IV 4.3 mg/kg over 6 hours x 3 days Level V 5.6 mg/kg over 6 hours x 2 days Level VI 6.4 mg/kg over 6 hours x 2 days

Drug: Busulfan

Dexamethasone 40 mg PO 1-4 Thalidomide 200 mg PO 1-6 Cisplatin* 10 mg/m, Continuous infusion 1-4 Adriamycin** 10 mg/m2, Continuous infusion 1-4 Cyclophosphamide 400 mg/2, Continuous infusion 1-4 Etoposide 40 mg/m2, Continuous infusion 1-4 All doses will be based on calculated body weight (actual weight + ideal body weight ÷ 2) and height, and not to exceed a BSA of 2.0 m2 The daily dose of cyclophosphamide, etoposide, and cisplatin will be mixed in a 1L bag of NS to be UAMS infused over 24 hours. Adriamycin will be mixed in at least 50cc D5W to be infused over 24 hours

Other Name: Busulfex

No Intervention: Usual care

Other: Usual care

no intervention

Detailed Description:

This trial will determine the maximal dose of Busulfex® that can be given in a two, three, or four day period with acceptable toxicity to myeloma patients, who either are > or = 65 years of age or have renal insufficiency, defined as creatinine > 3g/dL or creatinine clearance < 30 ml/min.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients must have symptomatic multiple myeloma requiring treatment
Patients must have been approved for single or tandem autologous transplant
Patients must be > or = 65 years of age or diagnosed with renal insufficiency, defined as having a creatinine > 3 mg/dl or a creatinine clearance < 30 ml/minute
Patients must not have a history of chronic obstructive or chronic restrictive pulmonary disease. Patients must have adequate pulmonary function studies > 50% of predicted on mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) > 50% of predicted,
Patients must have an ECHO or MUGA performed within 60 days prior to registration, LVEF > 40%.
Bilirubin, SGOT, SGPT must be less than 1.5 times the upper limit of normal
Patients must have evaluable myeloma marker for response such as: *Serum M protein >1g/dl or urine M protein >1g/24 hours and/or; *Bone marrow plasmacytosis with >20% plasma cells and/or; *Extramedullary plasmacytosis; *MRI/PET scan has focal lesions due to myeloma.
Patients must be able to receive full doses of DT-PACE, in the opinion of the treating investigator, with the exception of cisplatin.
Patients must have a performance status of 0-2 based on SWOG criteria unless the patient's status is due to active myeloma
All patients must be informed of the investigational nature of the study and have signed an IRB-approved informed consent in accordance with institutional and federal guidelines.

Exclusion Criteria:

Serum transaminases > 1.5 x ULN and direct bilirubin > 1.5 mg/dl
HIV positive or active Hepatitis B or Hepatitis C infection; (if serology is positive a quantitative PCR will be done).
Patients with a prior malignancy in whom life expectancy is more likely to be determined by the prior malignancy than the myeloma. Patients must not currently be receiving therapy for the prior malignancy.
Pregnant or nursing women. Women of childbearing potential must have a negative pregnancy test documented within one week of registration. Women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00113919

Locations

United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
University of Arkansas for Medical Sciences, Myeloma Institute for Research and Therapy
Little Rock, Arkansas, United States, 72205

Sponsors and Collaborators

University of Arkansas

Investigators

Principal Investigator:

Frits van Rhee, MD, PhD

UAMS

More Information

No publications provided

Responsible Party:	Naveen Kumar, CRA, University of Arkansas
ClinicalTrials.gov Identifier:	NCT00113919 History of Changes
Other Study ID Numbers:	2003-25
Study First Received:	June 10, 2005
Results First Received:	April 14, 2011
Last Updated:	June 20, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Arkansas:

Myeloma, MM

Additional relevant MeSH terms:

Multiple Myeloma
Neoplasms, Plasma Cell
Renal Insufficiency
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders

Immune System Diseases
Kidney Diseases
Urologic Diseases
Busulfan
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists

ClinicalTrials.gov processed this record on May 21, 2013