Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
CL1-78454-007
Study information
Scientific title
Phase I dose escalation study of oral administration of S 78454 given as monotherapy in the treatment of patients with refractory or relapsed acute myeloid leukemia, acute lymphoblastic leukemia or high or intermediary-2 risk myelodysplastic syndrome
Acronym
Study hypothesis
To establish the safety profile and the recommended Phase II dose of S 78454.
Ethics approval
Ethics approval was obtained before recruitment of the first participants
Study design
National multicentric dose escalation open Phase I study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details provided in the Interventions field to request a patient information sheet.
Condition
Acute myeloid leukemia, acute lymphoblastic leukemia or myelodysplastic syndrome.
Intervention
Capsules containing 20 mg and 100 mg of S 78454 / Oral use / Treatment duration is at the discretion of the investigator
Intervention type
Drug
Phase
Phase I
Drug names
S 78454
Primary outcome measure
1. DLTs and MTDs at the end of cycle 1 - methods used: blood samples, physical examination, bone marrow samples, ECG
2. Safety profile at each visit
Secondary outcome measures
1. Pharmacokinetic and pharmacodynamic evaluations on cycle 1 and cycle 2 by blood sample
2. Response evaluation during the study by blood samples and bone marrow samples
Overall trial start date
15/07/2012
Overall trial end date
30/09/2015
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Male or female patient aged > or equal to 18
2. Ability to swallow oral capsule(s)
3. Estimated life expectancy > 8 weeks
4. ECOG performance status < or equal to 2
5. Adequate renal and hepatic functions
6. Left ventricular ejection fraction within normal limits
7. Patients with AML as defined by WHO 2008 classification, excluding acute promyelocytic leukemia
8. Patients with high or intermediary risk (IPSS int-2) myelodysplastic syndrome (MDS) as defined by WHO 2008 classification and IPSS, who have failed hypomethylating therapy (5 azacytidine)
9. Patients with histologically or cytologically confirmed B-cell ALL as defined by WHO 2008 revised classification, excluding Philadelphia chromosome-positive (Ph+) ALL (or BCR-ABL+) and B-cell ALL 3 Burkitt like, who have failed conventional or investigational therapy
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
50 patients
Participant exclusion criteria
1. Major surgery within previous 4 weeks
2. Diagnosis of acute promyelocytic leukemia, Philadelphia chromosomepositive (Ph+) ALL (or BCR-ABL+) or B-cell ALL 3 Burkitt like
3. Patients who have not recovered from toxicity of previous antileukaemic therapy, including grade < or equal to 1 non-haematologic toxicity
4. Any previous chemotherapy for AML within at least 2 weeks (or at least 5 half-life whichever is longer), except for hydroxyureas which must be stopped within 24 hours before starting the study drug)
5. Neutrophil growth factor stimulating agent (G-CSF) within previous one week
6. Last dose of biological therapy or immunotherapy agent (therapeutic or diagnostic) less than 7 days prior to the first study drug intake
7. Any concurrent treatment with anticoagulants (curative or preventive),
8. Any radiotherapy within previous 4 weeks (except for palliative radiotherapy at localised lesions)
9. Patients with history of allogeneic stem cell transplant of less than 6 months or with active graft versus host disease requiring immune suppressive therapy
10. Patients with active disseminated intravascular coagulation (DIC) (plasma fibrinogen <1 g/L)
11. Presence of heart disorders or clinically significant heart diseases
12. Pregnant or breastfeeding women, women of child-bearing potential without effective contraception
Recruitment start date
15/07/2012
Recruitment end date
17/10/2014
Locations
Countries of recruitment
France
Trial participating centre
Institut Paoli Calmettes
Marseille CEDEX 9
13273
France
Sponsor information
Organisation
Pharmacyclics LLC (USA)
Sponsor details
999 East Arques Avenue
Sunnyvale
94085
United States of America
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
Pharmacyclics LLC (USA)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
1. 2012 results in https://www.ncbi.nlm.nih.gov/pubmed/23087409 (added 22/01/2019)