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Sirolimus Combined With Low-dose Warfarin for the Treatment of Refractory PNH

Primary Purpose

Paroxysmal Nocturnal Hemoglobinuria

Status
Unknown status
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
sirolimus
Sponsored by
Peking Union Medical College Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Paroxysmal Nocturnal Hemoglobinuria

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • age 18-70 years
  • diagnosed with PNH and no thrombosis
  • ineffective, relapsed or intolerant to conventional treatment (eg glucocorticoids, • • iron, folic acid, androgen, etc.)
  • not available for hematopoietic stem cell transplantation
  • ECOG≤2
  • agreed to sign the consent forms

Exclusion Criteria:

  • severe heart, liver and kidney dysfunction
  • combined with thrombotic complications
  • people who are pregnant and breastfeeding
  • history of other immunosuppressive agents in recent 3 months
  • Patients who are not eligible to participate in this trial due to any reason based • • • on the consideration of investigator

Sites / Locations

  • Peking union medical college hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Patients cohort

Arm Description

A total of 40 patients with refractory classic PNH will be included and will be intervened by a combined therapy including sirolimus and low-dose warfarin

Outcomes

Primary Outcome Measures

Hemoglobin
Hemoglobin in g/L

Secondary Outcome Measures

Short Form 36 items(SF-36) questionnaire
SF-36 questionnaire in scores

Full Information

First Posted
February 28, 2019
Last Updated
March 6, 2019
Sponsor
Peking Union Medical College Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03866681
Brief Title
Sirolimus Combined With Low-dose Warfarin for the Treatment of Refractory PNH
Official Title
Sirolimus Combined With Low-dose Warfarin for the Treatment of Refractory Classic Paroxysmal Nocturnal Hemoglobinuria ,a Prospective Study
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Unknown status
Study Start Date
April 1, 2019 (Anticipated)
Primary Completion Date
March 1, 2021 (Anticipated)
Study Completion Date
April 1, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking Union Medical College Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Classical paroxysmal nocturnal hemoglobinuria(PNH) is mainly characterized by hemolysis and thrombosis, which reduced patients ' quality of life(QoL) greatly and even lead to death. Glucocorticoids and symptomatic supportive therapy are traditional treatments and the response rate is far from satisfactory. Eculizumab is an effective therapy but it is expensive and not available in China mainland.The investigators aim to explore the efficacy and safety of sirolimus for refractory classic PNH.
Detailed Description
Classical paroxysmal nocturnal hemoglobinuria(PNH) is mainly characterized by hemolysis and thrombosis, which reduced patients ' quality of life(QoL) greatly and even lead to death. There is no ideal therapy except for eculizumab, expensive and not available in China mainland. Glucocorticoids and symptomatic supportive therapy are traditional treatments. The response rate is 30%, far from satisfactory. In recent years, T lymphocyte-mediated destruction of normal hematopoietic stem cells have been reported to involve the pathogenesis of PNH, making immunomodulatory drugs be potential effective treatments. Sirolimus (rapamycin), produced by the bacterium Streptomyces hygroscopicus, is a mammalian target of Rapamycin (mTOR) inhibitor. mTOR is a serine/threonine kinase that regulates cell growth, proliferation, metabolism and survival. It has two interacting complex, mTORC1 and mTORC2. Sirolimus primarily inhibits mTORC1, has been demonstrated for its immunomodulatory effects and ability to improve hematopoietic stem cell function. Recently, sirolimus has been reported to be effective and well tolerated in the treatment of immune-mediated cytopenias, even in multi-immunosuppressants resistant patients. In addition, classical PNH patients have a higher risk of thrombosis especially in refractory ones and it is reasonable to use low-dose warfarin in the management of patients with classic refractory PNH. In this study, it is anticipated to evaluate the effect of sirolimus combined with low-dose warfarin on patients with refractory classic PNH. The adverse effects and QoL on different time points were documented.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Paroxysmal Nocturnal Hemoglobinuria

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Patients cohort
Arm Type
Experimental
Arm Description
A total of 40 patients with refractory classic PNH will be included and will be intervened by a combined therapy including sirolimus and low-dose warfarin
Intervention Type
Drug
Intervention Name(s)
sirolimus
Other Intervention Name(s)
warfarin
Intervention Description
The dose of sirolimus is adjusted according to monitored serum concentration, maintain Rapamycin concentration ranging from 4 to 10ng/ml.Warfarin was administered orally at a dose of 1mg per day for a year,then gradually reduced to stop.
Primary Outcome Measure Information:
Title
Hemoglobin
Description
Hemoglobin in g/L
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Short Form 36 items(SF-36) questionnaire
Description
SF-36 questionnaire in scores
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: age 18-70 years diagnosed with PNH and no thrombosis ineffective, relapsed or intolerant to conventional treatment (eg glucocorticoids, • • iron, folic acid, androgen, etc.) not available for hematopoietic stem cell transplantation ECOG≤2 agreed to sign the consent forms Exclusion Criteria: severe heart, liver and kidney dysfunction combined with thrombotic complications people who are pregnant and breastfeeding history of other immunosuppressive agents in recent 3 months Patients who are not eligible to participate in this trial due to any reason based • • • on the consideration of investigator
Facility Information:
Facility Name
Peking union medical college hospital
City
Beijing
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bing Han, Doctor
Phone
+86-010-69155760
Email
hanbing_li@sina.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Sirolimus Combined With Low-dose Warfarin for the Treatment of Refractory PNH

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