Clinical trial NCT00131261: Clinical Trial of PXD101 in Patients With Advanced Multiple Myeloma
Official title: A Phase II Clinical Trial of PXD101 in Patients With Advanced Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Neoplasms
Lead sponsor: Valerio Therapeutics
Sponsor class: INDUSTRY
First posted: 2005-08-18
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this open-label, non-randomized trial is to assess the safety and effectiveness of PXD101, both alone and in combination with dexamethasone, in patients with advanced multiple myeloma. PXD101 is a new, potent histone deacetylase (HDAC) inhibitor. Various members of this class of drugs have shown activity in preclinical studies and in initial clinical trials of multiple myeloma and lymphoma. Furthermore, HDAC inhibitors, including PXD101, have been shown to sensitize myeloma cells to the killing effect of other chemotherapeutic agents, including dexamethasone, a well-established agent in relapsing myeloma.


Eligibility criteria: Inclusion criteria

1. Signed informed consent
2. A confirmed diagnosis of multiple myeloma, diagnostic criteria as follows, in patients who have failed at least two prior lines of therapy.

   Diagnostic criteria for multiple myeloma:

   A Monoclonal immunoglobulin (M-component) in serum of IgG-type \> 30 g/l, of IgA type \> 20 g/l, of IgD type or IgE type of any concentration and/or excretion of M-component in the urine of type k or l type \> 1 g/24 hours.

   B M-component in serum and/or urine in lower concentration than indicated above in 'A'.

   C 10% or more plasma cells in bone marrow aspirate or plasmocytosis in biopsy from bone marrow or soft tissue tumor D Osteolytical bone lesions.

   The diagnosis of multiple myeloma demands one of the following combinations: A+C, A+D, or B+C+D.
3. Evaluable disease (as defined above)
4. Adequate bone marrow and hepatic functions including the following:

   1. WBC \> 2.5 x 109/l, absolute neutrophil count ≥ 1.5 x 109/l, platelets ≥ 50x109/l
   2. Total bilirubin ≤1.5 x upper normal limit.
   3. AST (SGOT), ALT (SGPT) ≤2.5 x upper normal limit
5. Serum potassium within normal range.
6. Age ≥18 years
7. Performance status (PS) ≤2 (ECOG scale)
8. Estimated life expectancy greater than 3 months
9. Female patients with reproductive potential with a negative serum pregnancy test within the last 7 days before trial enrollment and use a safe contraceptive during and in a period of 60 days after the trial. Fertile female partners to male participants must likewise use contraceptive.

Exclusion criteria

1. Anticancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents within the last 4 weeks or a longer period depending on the defined characteristics of the agents used (e.g. 6 weeks for mitomycin or nitrosourea). Exception: bisphosphonates for bone disease caused by multiple myeloma.
2. Active infection or any medical condition likely to interfere with trial procedures.
3. Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension, congestive heart failure related to primary cardiac disease, a condition requiring anti-arrhythmic therapy, ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to the trial entry.
4. A marked baseline prolongation of QT/QTc interval, e.g., repeated demonstration of a QTc interval \>500; Long QT Syndrome; the required use of concomitant medication on PXD101 infusion days that may cause Torsade de Pointes. (See Appendix B for list).
5. Patients with renal insufficiency defined as a calculated creatinine clearance of \< 45 ml/min.
6. Clinically significant central nervous system disorders requiring neuroleptics or anti-convulsant medication.
7. Altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies
8. Other malignant diseases requiring treatment
9. Non-secretory multiple myeloma or symptomatic amyloidosis
10. Pregnant or breast-feeding women
11. Women of childbearing age and potential, who do not use effective contraception
12. Known HIV positivity

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: West Hollywood
country: United States
facility: James Berenson, MD, Inc
state: California
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: New York
country: United States
facility: Research Facility
state: New York
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Bergen
country: Norway
facility: Research Facility
city: Oslo
country: Norway
facility: Research Facility
city: Trondheim
country: Norway
facility: Research Facility
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Trust
city: Surrey
country: United Kingdom
facility: The Royal Marsden NHS Trust
Study officials:
affiliation: Valerio Therapeutics
name: enquiries@topotarget.com
role: STUDY_CHAIR
References: