A phase II Clinical Trial of PXD101 in Patients with Advanced Multiple Myeloma - PXD101-301-G

• Register: EUCTR
• Last refreshed on: 18 April 2012
• Main ID: EUCTR2004-002054-55-DK
• Date of registration: 23/09/2004
• Prospective Registration: Yes
• Primary sponsor: Topotarget A/S
• Public title: A phase II Clinical Trial of PXD101 in Patients with Advanced Multiple Myeloma - PXD101-301-G
• Scientific title: A phase II Clinical Trial of PXD101 in Patients with Advanced Multiple Myeloma - PXD101-301-G
• Date of first enrolment: 12/01/2006
• Target sample size: 50
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-002054-55
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Denmark, United Kingdom

Key inclusion & exclusion criteria

Inclusion 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 Osteolytic 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 described above)
4. Adequate bone marrow and hepatic function including the following:
WBC > 2.5 x 109/l, absolute neutrophil count = 1.5 x 109/l, platelets =50x109/l
Total bilirubin =1.5 x upper normal limit.
AST (SGOT), ALT (SGPT) =2.5 x upper normal limit
5. Serum potassium within normal range.
6. Age =18 years
7. ECOG performance status (PS) =2
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 for a period of 60 days after the trial. Fertile female partners to male participants must likewise use contraceptive.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
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. Co-existing active infection or any co-existing 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




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients in relapse from prior treatment, with histologically and otherwise verified diagnosis of multiple myeloma.

Intervention(s)

Product Name: PXD101
Product Code: PXD101
Pharmaceutical Form: Solution for infusion
CAS Number: 414864-00-9
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

Trade Name: Dexamethason 8 mg GALEN
Product Name: Dexamethason 8mg GALEN
Pharmaceutical Form: Tablet
INN or Proposed INN: Dexamethasone
CAS Number: 50-02-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 8-

Primary Outcome(s)

Secondary Objective: Study part A
• To examine time to response, duration of response, time to progression, and survival following single agent PXD101 therapy.
• To examine safety following single agent PXD101 therapy

Secondary objectives Study Part B

• To examine the chemotherapy sensitizing effect of PXD101 by assessing the efficacy (response rate, duration of response, time to progression and survival) and safety of a combination of dexamethasone and PXD101.
• To determine the pharmacokinetic parameters of the intravenous administration of PXD101 followed by oral dexamethasone on days 1 and 4.
• To investigate the pharmacodynamic effects of PXD101 in blood mononuclear cells on days 1 and 4, and when possible in tumor biopsies (bone marrow), in patients receiving PXD101 in combination with dexamethasone.

Main Objective: • In patients with advanced myeloma to assess the efficacy of PXD101 treatment (as measured by response rate (CR, PR, MR, NC/SD, PD) using the response criteria of Bladé et al Br.J.Haematol. 1998, 102: 1115-23)).

Primary end point(s): 10.3.1
The primary objective of the study is to determine the rates of OR and SD in multiple myeloma patients, refractory to prior therapy, after monotherapy with PXD101 and in combination with Dexamethasone. The primary target variable is therefore whether or not an individual patient shows confirmed CR, PR MR or SD. Descriptive statistics (incidence and confidence intervals) will be used to summarize the number of patients exhibiting an OR or SD in both parts of this study.

Secondary target variables include:
• time to response, duration of response, time to progression, time to next therapy and survival following single agent PXD101 therapy and combination therapy with Dexamethasone.
• safety parameters following single agent PXD101 therapy and combination therapy with Dexamethasone.
• pharmacokinetic estimates of PXD101 monotherapy and in combination with Dexamethasone.

Time to event parameters will be estimated using the Kaplan-Meier method. All reported symptoms and adverse advents would be coded according to the NCI-CTC coding system and presented and summarized by dose. Crude incidence rates will be based on the maximum intensity grade for each patient. All patients who receive any amount of PXD101 will be included in these analyses. 95% confidence intervals will be calculated where appropriate.

Secondary ID(s)

PXD101-301-G