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

NCT ID: NCT03336632

Last Updated: 2018-07-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-01
• Study Completion Date: 2021-03-30

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.

Conditions

Leukemia, Acute; MDS

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Chidamide

Chidamide, tablets, 5 mg/tablet, 20 mg orally twice weekly from D-7\~+14 Cyclophosphamide: 50 mg/Kg intravenously D+3, +4 Cyclosporine A: intravenously then orally 3 mg/Kg D+5\~D+100

Group Type: EXPERIMENTAL

Chidamide

Intervention Type: DRUG

20 mg orally, twice weekly from D-7 to D+14

Cyclophosphamide

Intervention Type: DRUG

50 mg/Kg intravenously D+3, +4

cyclosporine A

Intervention Type: DRUG

3 mg/Kg intravenously then orally from D+5 to D+100 if no acute graft-versus-host disease

Interventions

Chidamide

20 mg orally, twice weekly from D-7 to D+14

Intervention Type: DRUG

Cyclophosphamide

50 mg/Kg intravenously D+3, +4

Intervention Type: DRUG

cyclosporine A

3 mg/Kg intravenously then orally from D+5 to D+100 if no acute graft-versus-host disease

Intervention Type: DRUG

Other Intervention Names

HBI-8000; cyclosporine

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.

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sichuan University

OTHER

Sponsor Role: lead

Responsible Party

Jie Ji

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ting Liu, MD

Role: STUDY_CHAIR

West China Hospital

Locations

West China Hospital of Sichuan University

Chengdu, Sichuan, China

West China Hospital of Sichuan University

Chengdu, Sichuan, China

Countries

China

Central Contacts

Jie Ji, MD

Role: CONTACT

jieji@scu.edu.cn

86-28-85422373

Ting Liu, MD PHD

Role: CONTACT

liuting@scu.edu.cn

86-28-85422370

Facility Contacts

Jie Ji, MD

Role: primary

jieji@scu.edu.cn

86-28-85422370

Other Identifiers

HX-GVHD-1

Identifier Type: -

Identifier Source: org_study_id