Phase I study of S 78454 in the treatment of patients with acute myeloid leukemia, acute lymphoblastic leukemia or myelodysplastic syndrome

ISRCTN	ISRCTN99680465
DOI	https://doi.org/10.1186/ISRCTN99680465
Secondary identifying numbers	CL1-78454-007

Submission date: 04/10/2013
Registration date: 09/12/2013
Last edited: 22/01/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration and not expected to be available in the future

Contact information

Prof Norbert Vey
Scientific

Institut Paoli Calmettes
232 Boulevard Sainte Marguerite
Marseille CEDEX 9
13273
France

Study information

Study design	National multicentric dose escalation open Phase I study
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details provided in the Interventions field to request a patient information sheet.
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
Study objectives	To establish the safety profile and the recommended Phase II dose of S 78454.
Ethics approval(s)	Ethics approval was obtained before recruitment of the first participants
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Phase I
Drug / device / biological / vaccine name(s)	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 study start date	15/07/2012
Completion date	30/09/2015

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	50 patients
Key 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
Key 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
Date of first enrolment	15/07/2012
Date of final enrolment	17/10/2014

Locations

Countries of recruitment

France

Study participating centre

Institut Paoli Calmettes

Marseille CEDEX 9
13273
France

Sponsor information

Pharmacyclics LLC (USA)
Industry

999 East Arques Avenue
Sunnyvale
94085
United States of America

Website	www.pharmacyclics.com
"ROR"	https://ror.org/03hm8w204

Funders

Funder type

Industry

Pharmacyclics LLC (USA)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	15/01/2013	22/01/2019	Yes	No

Editorial Notes

22/01/2019: Publication reference added

On 31/03/2015 the overall trial end date was changed from 30/12/2014 to 30/12/2015.

On 17/12/2015 the following changes were made to the trial record:
1. Sponsoring/funding responsibility for the S 78454 project was transferred from Servier, France to Pharmacyclics, USA on 23/11/2014.
2. The overall trial end date was changed from 30/12/2015 to 30/09/2015.