Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

UCMSCs as Front-line Approach of Treatment for Patients With aGVHD (GVHD Cyto-MSC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03847844
Recruitment Status : Recruiting
First Posted : February 20, 2019
Last Update Posted : February 20, 2019
Sponsor:
Collaborators:
Universiti Tunku Abdul Rahman
Ministry of Energy, Science, Technology, Environment and Climate Change, Malaysia
Information provided by (Responsible Party):
Cytopeutics Sdn. Bhd.

Brief Summary:

Background: Graft-versus-host disease (GVHD) is a devastating complication following allogeneic hematopoietic stem cell transplantation (HSCT) mediated by stimulation of antigen presenting cells (APCs) which leads to donor T-lymphocytes activation and target tissue destruction, particularly affecting the skin, gastrointestinal tract, and liver in acute setting. In recent years, researchers have discovered that the application of mesenchymal stromal cells (MSCs) as salvage treatment among steroid refractory GVHD patients improves outcomes without long-term risk association. On the other hand, the use of MSCs concurrently with steroids as front-line treatment for acute GVHD has yet to be researched on. The investigators hypothesize that this approach, as the MSCs will be administered at earlier stage of the disease, will increase survival rate and reduce mortality among aGVHD patients.

Objective: In this study, the investigators aim to determine the efficacy and safety of allogeneic infusion of Cytopeutics® umbilical cord-derived mesenchymal stromal cells (Cyto-MSC) in combination of standard corticosteroid therapy as front-line approach for treatment of grade II-IV acute GVHD patients.

Study design: This is a phase I/II clinical study involving patients who underwent an allogeneic HSCT for malignant or non malignant haematological disorders and developed grade II-IV acute GVHD. A total of 40 eligible patients will be recruited in this study.

For Phase I open labelled study, 5 eligible patients will be recruited to receive Cyto-MSC (5 million UC-MSCs per kg bodyweight) and standard treatment. Meanwhile, for Phase II double blinded placebo controlled study, another 35 eligible patients will be recruited and randomized into 2 study groups where 15 patients will be assigned into Group A to receive Cyto-MSC (5 million UCMSCs per kg bodyweight) and standard treatment, meanwhile another 20 patients will be assigned into Group B to receive Placebo and standard treatment.

Cyto-MSC or Placebo will be administered at Day 1 and Day 4. Another infusion of Cyto-MSC or Placebo will be given at Day 7 if the patient shows no or partial response based on GvHD grading criteria. All patients will be assessed up until 6 months follow-up which include medical history, clinical and physical evaluations, pathology investigations, biomarkers and immune cell subsets analysis, as well as quality of life questionnaires.


Condition or disease Intervention/treatment Phase
Acute-graft-versus-host Disease Biological: Umbilical cord derived mesenchymal stem cell Other: Placebo Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Cytopeutics® Umbilical Cord Mesenchymal Stem Cells (Cyto-MSC) for Patients With Grade II -IV Acute Graft-Versus-Host Disease: A Phase I/II Clinical Study
Actual Study Start Date : February 1, 2019
Estimated Primary Completion Date : October 31, 2021
Estimated Study Completion Date : December 31, 2021


Arm Intervention/treatment
Experimental: Group A
Cyto-MSC (5 million UCMSCs per kg bodyweight) and standard treatment
Biological: Umbilical cord derived mesenchymal stem cell
Umbilical cord derived mesenchymal stem cell
Other Name: Cyto-MSC

Placebo Comparator: Group B
Placebo (normal saline) and standard treatment
Other: Placebo
Normal saline




Primary Outcome Measures :
  1. Rate of Complete Response (CR) at Day 28 [ Time Frame: 28 days ]
  2. Rate of Partial Response (PR) at Day 28 [ Time Frame: 28 days ]
  3. Rate of PR and CR at Day 14 [ Time Frame: 14 days ]
  4. Percentage of patient requiring MMF rescue during treatment [ Time Frame: 6 months ]
  5. Rate of long term complication incidence [ Time Frame: 6 months ]
  6. Rate of chronic clinical response incidence [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Overall survival (OS) rate at 3 months [ Time Frame: 3 months ]
  2. Correlation between response to Cyto-MSC at Day 14 and Day 28 to survival at 90 days [ Time Frame: 90 days ]
  3. Relapse-free survival at 3 months [ Time Frame: 3 months ]
  4. Disease relapse at 3 months [ Time Frame: 3 months ]
  5. Incidence of infection [ Time Frame: 6 months ]
  6. Incidence of CMV reactivation [ Time Frame: 6 months ]
  7. Measurement quality of life of cancer patients by using EORTC QLQ-C30 questionnaire [ Time Frame: 6 months ]
    The final score ranges from 0 (better outcome) to 126 (worse outcome)

  8. Measurement quality of life in bone marrow transplantation by using FACT-BMT questionnaire [ Time Frame: 6 months ]
    The final score ranges from 0 (better outcome) to 164 (worse outcome)

  9. Measurement of health-related quality of life in children and young people by using PEDsQL questionnaire (patients age less than 18 years old) [ Time Frame: 6 months ]
    The final score ranges from 0 (better outcome) to 92 (worse outcome)

  10. Measurement of generic health status among patients by using EQ-5D questionnaire [ Time Frame: 6 months ]
    The final score ranges from 0 (better outcome) to 100 (worse outcome)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient age 16 and above
  • Patient who has undergone an allogeneic haematopoietic stem cell transplantation (HSCT) receiving allograft either from HLA-matched related donor (MRD), HLA-matched unrelated donor (MUD), Unrelated Cord Blood (UCB) or Haploidentical donor and developed grade II-IV acute graft versus host disease (acute GVHD) involving the skin, GI tract and/or liver based on 1994 Consensus Conference on Acute GVHD Grading
  • Patient and/or parent(s) or legal guardian(s) and assent form signed informed consent. Assent form will be obtained for patients aged less than 18 years. Investigators will obtain the permission of the parents or guardians for the participation of the minor in the research, and to solicit assent from the minor

Exclusion Criteria:

  • Patient who has enrolled in another investigational drug trial or stem cell related trial or has completed the aforesaid within (3) months
  • Patient with HIV or syphilis (Patient should be screened for HIV and VDRL up to 6 months prior to study start)
  • Patient with Hepatitis B (HBV) or Hepatitis C (HCV). All patients must be screened for HBV and HCV up to 6 months prior to study start using the routine hepatitis virus laboratory. Patients who are positive for HBsAg or HBcAb will be eligible if they are negative for HBV-DNA, these patients should receive prophylactic antiviral therapy. Patients who are positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA
  • Patient has creatinine clearance of ≤50mL/min or creatinine is ≥200 µmol/L
  • Patient had undergone or on other immune-modulatory treatments such as interferon or Thalidomide over the last 12 months
  • Patient with progressive underlying disease or not in complete remission (CR) at the time of transplant
  • Any other severe co-morbidities which the doctor deems as a contraindication to cell therapy
  • Adults under law protection or without ability to consent
  • The patient has previous history or on-going psychiatric illness
  • Patient has received an HSCT transplant for a solid tumor disease
  • Patient has a known hypersensitivity to dimethyl sulfoxide (DMSO)
  • Patient is a female who is pregnant, lactating, or is planning a pregnancy during study participation, or in the follow-up period

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03847844


Contacts
Layout table for location contacts
Contact: Sze Piaw Chin +60386881098 research@cytopeutics.com
Contact: Mohd Shahrizal Mohd Yusoff +60386881098 research@cytopeutics.com

Locations
Layout table for location information
Malaysia
Hospital Ampang Recruiting
Ampang, Selangor, Malaysia, 68000
Contact: Syed Carlo Edmund    +60102259506    syedcarlo@crc.gov.my   
Principal Investigator: Sen Mui Tan         
Sub-Investigator: Sharifah Shahnaz Syed Abd Kadir         
Sub-Investigator: Kim Wah Ho         
Sub-Investigator: Azizan Sharif         
Sub-Investigator: Tze Shin Leong         
Sponsors and Collaborators
Cytopeutics Sdn. Bhd.
Universiti Tunku Abdul Rahman
Ministry of Energy, Science, Technology, Environment and Climate Change, Malaysia
Investigators
Layout table for investigator information
Principal Investigator: Sen Mui Tan Hospital Ampang

Layout table for additonal information
Responsible Party: Cytopeutics Sdn. Bhd.
ClinicalTrials.gov Identifier: NCT03847844     History of Changes
Other Study ID Numbers: POD0030/CP/R
First Posted: February 20, 2019    Key Record Dates
Last Update Posted: February 20, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Graft vs Host Disease
Immune System Diseases