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Phase I/II dose-escalation study of S 78454 in Lymphoma

Phase 1
Conditions
Hodgkin's disease (HD) , non-Hodgkin lymphoma (NHL) and chronic lymphocytic Leukaemia (CLL)
MedDRA version: 19.0Level: PTClassification code 10029547Term: Non-Hodgkin's lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 19.0Level: PTClassification code 10020206Term: Hodgkin's diseaseSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 19.0Level: LLTClassification code 10008993Term: Chronic lymphoid leukaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2009-013691-47-BE
Lead Sponsor
Pharmacyclics. LLC
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
156
Inclusion Criteria

- HD or NHL that has relapsed or is refractory to conventional, standard form of therapy.
- CLL that has relapsed or is refractory to conventional, standard form of therapy.
- Ability to swallow oral capsule(s) without difficulty.
- Estimated life expectancy > 12 weeks.
- ECOG performance status = 2.
- Adequate haematological, renal, hepatic and cardiac functions.
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 71
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 85

Exclusion Criteria

- Allogeneic bone marrow transplant.
- Major surgery within previous 4 weeks.
- Concurrent therapeutic anticoagulation by AVK.
- Patient previously treated by another HDAC Inhibitor than valproic acid (Phase II part).
- Corticosteroids > 20 mg prednisone equivalent per day within previous 10 days.
- Immunotherapy, chemotherapy (nitrosoureas within 6 weeks) or radiotherapy within previous 4 weeks.
- Patients treated by valproic acid within previous 5 days.
- Any other previous (in the last 3 years) or concurrent cancer, other than resected non melanoma skin cancer or cancer in situ of the uterine cervix.
- Risk factors for, or use of drugs known to prolong QTc interval or that may be associated with Torsades de Pointes.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: Phase I part:<br>- To assess the MTDs and the dose-limiting toxicities (DLTs) for each dosing schedule tested.<br>- To determine the optimal dosing schedule and its associated recommended Phase II dose.<br><br>Phase II part:<br>- To assess the objective response rate at the recommended dose of the optimal dosing schedule defined in the phase I part.;Secondary Objective: Phase I part:<br>- To determine the PK and PD profiles.<br>- To measure tumour response.<br><br>Phase II part:<br>- To assess the safety and tolerability.<br>- To assess the activity profile of S78454.<br>- To determine the PK and PD profiles.;Primary end point(s): - Phase I part : DLTs and MTDs.<br>- Phase II part: Objective response rate (ORR).;Timepoint(s) of evaluation of this end point: - DLTs and MTDs: at each visit.<br>- ORR : overall
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s): - Safety<br>- PK parameters<br>- Acetylation state (histones) of proteins<br><br><br> ;Timepoint(s) of evaluation of this end point: - Safety : at each visit<br>- PK parameters: during the cycle 1<br>- Acetylation state (histones) of proteins: during the cycle 1
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