Clinical trial NCT03336632: Chidamide Plus PTCy/Cyclosporine to Prevent GVHD After Myeloablative Conditioning, Matched PBSCT
Official title: Chidamide Plus Post-transplantation Cyclophosphamide and Cyclosporine to Prevent Graft-versus-host Disease After Myeloablative Conditioning, Matched Peripheral-blood Stem-cell Transplantation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Leukemia, Acute
MDS
Keywords: PBSCT
myeloablative conditioning
HDACi
chidamide
Lead sponsor: Sichuan University
Sponsor class: OTHER
First posted: 2017-11-08
Enrollment: 50
Sex: ALL
Minimum age (years): 16
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is to explore the efficacy and safety of introduction of chidamide in PTCy based GVHD prophylaxis in patients undergoing allogeneic PBSCT.

Detailed description: Eligible patients were aged 16 to 65 years, diagnosed with hematologic malignancy, and had a Karnofsky performance score of ≥70% and were candidates for myeloablative HCT. A 8/8 HLA allelic match between the donor and the recipient at HLA-A, HLA-B, HLA-C, and HLA-DRB1 by high-resolution typing was required. The graft source was PBSC.

Patients received a myeloablative conditioning regimen consisting of oral chidamide given twice weekly at a dose of 20 mg from day -7 to 2 weeks post transplantation, intravenous busulfan 3.2 mg/kg from day -6 to -3, intravenous fludarabine 30 mg/m2 and cytarabine 1g/m2 respectively from day -6 to -2. PBSCs were infused on day 0. GVHD prophylaxis was post-transplantation cyclophosphamide (50 mg/kg on day +3, +4) and cyclosporine (started from day +5). In the absence of GVHD, cyclosporine tapering started on day +100 and discontinued on day +180. Minimal residual disease (MRD) was determined by multi-parameter flow cytometry.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 16 years or older, and ≤ 65 years at time of enrollment
2. Signed informed consent
3. Hematologic disorder requiring allogeneic hematopoietic cell transplantation
4. Left ventricular ejection fraction (LVEF) ≥ 45% by multiple uptake gated acquisition (MUGA) scan or echocardiogram
5. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and diffusing lung capacity oxygenation (DLCO) adjusted ≥ 50% of predicted values on pulmonary function tests
6. Transaminases (AST, ALT) \< 3 times upper limit of normal (ULN) values
7. Creatinine clearance calculated ≥ 50 mL/min
8. Karnofsky Performance Status Score ≥ 60%.
9. Human leukocyte antigen (HLA) matched 8/ (A, B, C, DRB1) related or unrelated donor

Exclusion Criteria:

1. Active infection not controlled with appropriate antimicrobial therapy HIV, hepatitis B (HBcAb positive but HBsAg negative with undetectable viral load are eligible), or hepatitis C infection
2. Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) ≥4
3. Anti-thymocyte globulin (ATG) as part of the conditioning regimen
4. Pregnancy
5. Histone deacetylase (HDAC), DAC, HSP90 inhibitors or valproic acid for the treatment of cancer within 30 days
6. Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first chidamide treatment
7. Impaired cardiac function or clinically significant cardiac diseases, including any one of the following: Any history of ventricular fibrillation or torsade de pointes; Bradycardia defined as heart rate (HR)\< 45 bpm (Patients with pacemakers are eligible if HR ≥ 45 bpm); Screening electrocardiogram (ECG) with a QTcF \> 480 msec; Right bundle branch block + left anterior hemiblock (bifascicular block); Patients with myocardial infarction or unstable angina ≤ 12 months prior to starting study drug; Other clinically significant heart disease (e.g., New York Heart Association (NYHA) class III or IV , uncontrolled hypertension) as per discretion of principal investigator and/or treating physician; Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug with the exception of drugs listed on Appendix B of study documents that are required for hematopoietic cell transplantation (HCT) patients.

Primary outcomes:
measure: aGVHD
timeFrame: 100 day after infusion of PBSCs
Secondary outcomes:
measure: GRFS
timeFrame: 3 years after recruitment
measure: DFS
timeFrame: 3 years after recruitment
measure: OS
timeFrame: 3 years after recruitment
measure: cGVHD
timeFrame: 2 yeas after infusion of PBSCs
Other outcomes:
Locations:
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
Study officials:
affiliation: West China Hospital
name: Ting Liu, MD
role: STUDY_CHAIR
References: