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Status unknownNCT03336632Updated Jul 18, 2018

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

A Phase 2 interventional study of Chidamide and Cyclophosphamide in Leukemia, Acute and MDS, sponsored by Sichuan University. Status unknown at 2 sites in China. Open to participants aged 16 Years to 65 Years. Per ClinicalTrials.gov, last updated 2018-07-18.

Sponsored by Sichuan University · Phase 2, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Jul 2018), so the status shown — last known as Not yet recruiting — may be out of date.
Phase
Phase 2
Study type
Interventional
Enrollment
50
Allocation
Not applicable
Ages
16 Years to 65 Years
Sex
All
01

Study summary

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

Read the 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.

02

Conditions studied

  • Leukemia, Acute
  • MDS

Keywords

  • PBSCT
  • myeloablative conditioning
  • HDACi
  • chidamide
03

Who can participate

Ages eligible
16 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
50 participants (estimated)

Study arms

  • Experimental
    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

    Drug: Chidamide · Drug: Cyclophosphamide · Drug: cyclosporine A

Interventions

  • DrugChidamide

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

    Also known as: HBI-8000

  • DrugCyclophosphamide

    50 mg/Kg intravenously D+3, +4

  • Drugcyclosporine A

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

    Also known as: cyclosporine

05

What researchers measure

Primary outcomes

  1. aGVHD

    accumulated incidence of aGVHD

    Time frame: 100 day after infusion of PBSCs

Secondary outcomes

  1. GRFS

    GVHD free, relapse free survival

    Time frame: 3 years after recruitment

  2. DFS

    Disease free survival

    Time frame: 3 years after recruitment

  3. OS

    Overall survival

    Time frame: 3 years after recruitment

  4. cGVHD

    accumulated incidence of cGVHD

    Time frame: 2 yeas after infusion of PBSCs

06

Study locations

2 sites
  • West China Hospital of Sichuan University
    Chengdu, Sichuan 610044, China
  • West China Hospital of Sichuan University
    Chengdu, Sichuan 610044, China
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03336632
Lead sponsor
Sichuan University
Responsible party
Jie Ji (MD, Sichuan University) — Principal investigator
First posted
Nov 8, 2017
Start date
Jan 1, 2019 (estimated)
Primary completion
Dec 30, 2020 (estimated)
Completion
Mar 30, 2021 (estimated)
Last update
Jul 18, 2018

Study contacts

Jie Ji, MD
Contact
jieji@scu.edu.cn
86-28-85422373
Ting Liu, MD PHD
Contact
liuting@scu.edu.cn
86-28-85422370
Ting Liu, MD
study chair · West China Hospital

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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