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 |
| Protocol serial number | CL1-78454-007 |
| Sponsor | Pharmacyclics LLC (USA) |
| Funder | Pharmacyclics LLC (USA) |
- 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
Scientific
Institut Paoli Calmettes
232 Boulevard Sainte Marguerite
Marseille CEDEX 9
13273
France
Study information
| Primary study design | Interventional |
|---|---|
| Study design | National multicentric dose escalation open Phase I study |
| Secondary study design | Randomised controlled trial |
| Study type | Participant 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 |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | S 78454 |
| Primary outcome measure(s) |
1. DLTs and MTDs at the end of cycle 1 - methods used: blood samples, physical examination, bone marrow samples, ECG |
| Key secondary outcome measure(s) |
1. Pharmacokinetic and pharmacodynamic evaluations on cycle 1 and cycle 2 by blood sample |
| Completion date | 30/09/2015 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | All |
| Target sample size at registration | 50 |
| 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
13273
France
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | 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 |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
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.
