Study of Combination PS-341 and Thalidomide in Multiple Myeloma - Full Text View

Sponsor:	University of Arkansas
Information provided by:	University of Arkansas
ClinicalTrials.gov Identifier:	NCT00083460

Purpose

The purpose of this study is to assess the toxicity of PS-341 combined with one of four doses of thalidomide in patients with refractory multiple myeloma, and to find the most appropriate doses of PS-341 and thalidomide in the combination.

Condition	Intervention	Phase
Multiple Myeloma	Drug: PS-341 Drug: Thalidomide Drug: Dexamethasone	Phase I

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	UARK 2001-37, A Phase I Exploratory Study of Combination PS-341 and Thalidomide in Refractory Multiple Myeloma

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Multiple Myeloma

Drug Information available for: Dexamethasone Thalidomide Dexamethasone acetate Doxiproct plus Bortezomib Dexamethasone Sodium Phosphate

U.S. FDA Resources

Further study details as provided by University of Arkansas:

Primary Outcome Measures:

Assess the toxicity of PS-341 combined with one of four doses of thalidomide in patients with refractory multiple myeloma [ Time Frame: until pt progresses or unexceptible toxicity ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	80
Study Start Date:	December 2001
Estimated Study Completion Date:	April 2013
Estimated Primary Completion Date:	November 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator	Drug: PS-341 Arm 1 a dose of 1.0mg/m2. Arm 2 a dose of 1.3mg/m2 Drug: Thalidomide In cohort 1, a dose of 50mg for cycles 2-8. Cohort 2, 100mg for cycles 2-8. Cohort 3, 150mg for cycles 2-8. Cohort 4, 200mg for cycles 2-8. Drug: Dexamethasone A dose of 20mg for cylces 3-8.
2: Active Comparator	Drug: PS-341 Arm 1 a dose of 1.0mg/m2. Arm 2 a dose of 1.3mg/m2 Drug: Thalidomide In cohort 1, a dose of 50mg for cycles 2-8. Cohort 2, 100mg for cycles 2-8. Cohort 3, 150mg for cycles 2-8. Cohort 4, 200mg for cycles 2-8. Drug: Dexamethasone A dose of 20mg for cylces 3-8.

Detailed Description:

Patients will be enrolled in groups of 6-10 patients, each receiving a low dose of PS-341 (1.0 mg/m2) and different dose levels of thalidomide (50, 100, 150, and 200 mg). The first six patients in each group will receive PS-341 alone for the first cycle, and thalidomide will be added on day 22. If the combination is found to be safe in these first 6 patients, the remaining patients in each group will be enrolled. Initially, these patients will receive PS-341 alone and thalidomide will be added subsequently, if deemed safe based on the first 6 patients in each thalidomide dose cohort.

Eligibility

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

Criteria

Inclusion Criteria:

History of histologically documented multiple myeloma with relapsed or resistant disease, defined as previously treated with/without autologous stem cell transplantation and is either relapsing or is resistant after > 1 line of prior therapy for myeloma
Patients can not be eligible for MTRC phase III protocols of higher priority
Performance status of greater than or equal to 2 as per SWOG scale
Patients must have an absolute neutrophil count > 750/mm3, and a platelet count greater than or equal to 25,000/mm3
No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for at least three years. Prior malignancy is acceptable provided there has been no evidence of disease within the three-year interval
Pregnant or nursing women may not participate. Women of childbearing potential must have a negative pregnancy documented within one week of registration. Women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
Male or female adults of at least 18 years of age.
Signed written informed consent and willingness to meet follow-up schedule and study procedure obligations

Exclusion Criteria:

Chemotherapy or radiotherapy received within the previous 2 weeks
Prior Treatment of PS-341
Significant neurotoxicity, defined as grade greater than or equal to 2 neurotoxicity per NCI Common Toxicity Criteria
POEMS Syndrome
Non-secretory multiple myeloma
Active infection requiring antibiotics
Clinically significant hepatic dysfunction in the absence of liver metastases as noted by bilirubin or AST >3 times the upper normal limit or clinically significant concurrent hepatitis
New York Hospital Association (NYHA) Class III or Class IV heart failure
Myocardial infarction within the last 6 months
Poorly controlled hypertension, diabetes mellitus, or other serious or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol
Severe renal dysfunction defined as a creatinine clearance < 20 cc/min.
Absolute neutrophil count < 750/mm3, and a platelet count < 25,000/mm3
Pregnant or potential for pregnancy
Breast-feeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00083460

Locations

United States, Arkansas
University of Arkansas for Medical Sciences/MIRT
Little Rock, Arkansas, United States, 72205

Sponsors and Collaborators

University of Arkansas

Investigators

Principal Investigator:

Barlogie Barthel, M.D. Ph.D

University of Arkanas for Medical Sciences website

More Information

Additional Information:

Myeloma Institute for Research & Therapy website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	University_Of_Arkansas ( Brooke Carter, CRA )
Study ID Numbers:	UARK 2001-37
Study First Received:	May 24, 2004
Last Updated:	December 19, 2007
ClinicalTrials.gov Identifier:	NCT00083460 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Arkansas:

Multiple Myeloma
Thalidomide
Velcade

PS-341
Refractory
Bortezomid

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Dexamethasone
Anti-Infective Agents
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Thalidomide
Antineoplastic Agents
Blood Protein Disorders
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Paraproteinemias
Hemostatic Disorders
Hormones
Anti-Bacterial Agents

Hemorrhagic Disorders
Therapeutic Uses
Cardiovascular Diseases
Growth Inhibitors
Angiogenesis Modulating Agents
Dexamethasone acetate
Immunoproliferative Disorders
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Hematologic Diseases
Growth Substances
Bortezomib
Gastrointestinal Agents
Vascular Diseases

ClinicalTrials.gov processed this record on November 25, 2009