Chidamide Plus PTCy/Cyclosporine to Prevent GVHD After Myeloablative Conditioning, Matched PBSCT

MDS Clinical Trial

Official title:

Chidamide Plus Post-transplantation Cyclophosphamide and Cyclosporine to Prevent Graft-versus-host Disease After Myeloablative Conditioning, Matched Peripheral-blood Stem-cell Transplantation

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03336632
• Other study ID #: HX-GVHD-1
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: January 1, 2019
• Est. completion date: March 30, 2021

Study information

• Verified date: July 2018
• Source: Sichuan University
• Contact: Jie Ji, MD
• Phone: 86-28-85422373
• Email: jieji[@]scu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: March 30, 2021
• Est. primary completion date: December 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Leukemia, Acute
• MDS

Intervention

Drug:
• Chidamide
20 mg orally, twice weekly from D-7 to D+14
• Cyclophosphamide
50 mg/Kg intravenously D+3, +4
• cyclosporine A
3 mg/Kg intravenously then orally from D+5 to D+100 if no acute graft-versus-host disease

Locations

Country	Name	City	State
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	West China Hospital of Sichuan University	Chengdu	Sichuan

Sponsors (1)

Lead Sponsor	Collaborator
Sichuan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	aGVHD	accumulated incidence of aGVHD	100 day after infusion of PBSCs
Secondary	GRFS	GVHD free, relapse free survival	3 years after recruitment
Secondary	DFS	Disease free survival	3 years after recruitment
Secondary	OS	Overall survival	3 years after recruitment
Secondary	cGVHD	accumulated incidence of cGVHD	2 yeas after infusion of PBSCs