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Prevention of Acute Graft Versus Host Disease in Patients Undergoing Allogeneic ApoGraft Stem Cell Transplantation

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02828878
Recruitment Status : Unknown
Verified November 2019 by Cellect Biotechnology.
Recruitment status was:  Recruiting
First Posted : July 12, 2016
Last Update Posted : November 26, 2019
Sponsor:
Information provided by (Responsible Party):
Cellect Biotechnology

Tracking Information
First Submitted Date  ICMJE July 4, 2016
First Posted Date  ICMJE July 12, 2016
Last Update Posted Date November 26, 2019
Study Start Date  ICMJE January 2017
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 8, 2017)
Overall incidence, frequency and severity of adverse events (AEs) potentially related to the product during the study [ Time Frame: 180 days from transplantation ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 7, 2016)
Overall incidence, frequency and severity of adverse events (AEs), potentially related to the product during the study. [ Time Frame: 100 days from transplantation ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 8, 2017)
  • Determination of the optimal dose of FasL concentration that facilitates the biological activity of the ApoGraft process [ Time Frame: 180 days from transplantation ]
  • Time of neutrophils engraftment determined by number of days for reaching first of 3 consecutive days with ANC ≥ 500/mm3 [ Time Frame: 28 days from transplantation ]
  • Rate of neutrophils engraftment determined by number of days for reaching first of 3 consecutive days with ANC ≥ 500/mm3 [ Time Frame: 28 days from transplantation ]
  • Time of platelets engraftment determined by number of days for reaching first of 3 consecutive days with platelets ≥ 20,000/mm3 in the absence of platelet administration during the prior 7 days [ Time Frame: 180 days from transplantation ]
  • Rate of platelets engraftment determined by number of days for reaching first of 3 consecutive days with platelets ≥ 20,000/mm3 in the absence of platelet administration during the prior 7 days [ Time Frame: 180 days from transplantation ]
  • Incidence to development of aGvHD [ Time Frame: 180 days from transplantation ]
  • Time to development of aGvHD [ Time Frame: 180 days from transplantation ]
  • Non-relapse mortality [ Time Frame: 180 days from transplantation ]
  • Proportion of patients with disease relapse [ Time Frame: 180 days from transplantation ]
  • Proportion of patients with progression free and overall survival [ Time Frame: 180 days from transplantation ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 7, 2016)
  • Determination of the maximum tolerated dose of ApoGraft in subjects undergoing allogeneic bone marrow transplantation. [ Time Frame: 180 days from transplantation ]
  • Determination of the dose limiting toxicity of ApoGraft in subjects undergoing allogeneic bone marrow transplantation. [ Time Frame: 180 days from transplantation ]
  • Time of engraftment of neutrophils determined by number of days for reaching first of 3 consecutive days with ANC ≥ 500/mm3 without G-CSF support for 3 days. [ Time Frame: 28 days from transplantation ]
  • Rate of engraftment of neutrophils determined by number of days for reaching first of 3 consecutive days with ANC ≥ 500/mm3 without G-CSF support for 3 days. [ Time Frame: 28 days from transplantation ]
  • Time of engraftment of platelets determined by number of days for reaching first of 3 consecutive days with platelets ≥ 20,000/mm3 in the absence of platelet administration during the prior 7 days. [ Time Frame: 40 days from transplantation ]
  • Rate of engraftment of platelets determined by number of days for reaching first of 3 consecutive days with platelets ≥ 20,000/mm3 in the absence of platelet administration during the prior 7 days. [ Time Frame: 40 days from transplantation ]
  • Time of engraftment of ApoGraft product determined by proportion of patients reaching ANC levels ≥ 500/mm3 and platelets ≥ 20,000/mm3 for 3 consecutive days without G-CSF support for 3 days and platelet administration for previous 7 days [ Time Frame: 40 days from transplantation ]
  • Rate of engraftment of ApoGraft product determined by proportion of patients reaching ANC levels ≥ 500/mm3 and platelets ≥ 20,000/mm3 for 3 consecutive days without G-CSF support for 3 days and platelet administration for previous 7 days [ Time Frame: 40 days from transplantation ]
  • Chimerism rate at day 28, 100 and 180. [ Time Frame: 180 days from transplantation ]
  • Incidence of aGvHD at day 100 and 180. [ Time Frame: 180 days from transplantation ]
  • Grade and stage of aGvHD according to NIH criteria 2005; current and maximal score at day 100 and 180. [ Time Frame: 180 days from transplantation ]
  • Time to development of aGVHD [ Time Frame: 180 days from transplantation ]
  • Incidence of cGVHD by day 180 [ Time Frame: 180 days from transplantation ]
  • Grade and stage of cGVHD according to NIH criteria 2005; current and maximal score at day 180. [ Time Frame: 180 days from transplantation ]
  • Time to development of cGVHD [ Time Frame: 180 days from transplantation ]
  • Transplant-related mortality on day 100 and 180. [ Time Frame: 180 days from transplantation ]
  • Proportion of patients with disease relapse at days 100 and 180. [ Time Frame: 180 days from transplantation ]
  • Proportion of patients with overall survival at days 28,100 and 180. [ Time Frame: 180 days from transplantation ]
  • Incidence of infections (bacterial, fungal and viral) during study follow-up. [ Time Frame: 180 days from transplantation ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Prevention of Acute Graft Versus Host Disease in Patients Undergoing Allogeneic ApoGraft Stem Cell Transplantation
Official Title  ICMJE An Open-Label Phase I/II, Pilot, Staggered Four-Cohort Safety and Proof-of-Concept Study of ApoGraft in the Prevention of Acute Graft Versus Host Disease (aGvHD)
Brief Summary Interventional, open label, Phase I/II, Safety and Proof-of-Concept Study, with a follow up period of 180 days after the transplantation of ApoGraft.
Detailed Description

ApoGraft product is a mobilized peripheral blood cell product of a matched Related donor, collected via apheresis, which is exposed to the apoptotic mediator Fas Ligand (CD95L) prior to transplantation (Ex Vivo).

The study is designed to address the aspects of engraftment and Prevention of Acute Graft versus Host Disease (aGvHD) rate and/or severity in 12 Patients

STUDY DESIGN:

This is a phase 1/2, open-label, proof-of-concept, staggered 4-cohort clinical study. Each cohort will include 3 patients with hemato-oncology disorders eligible for allogeneic HLA-matched HSCT. Patients in all cohorts will undergo similar study procedures and evaluation. The cohorts will differ from each other in the amount of apoptotic mediator Fas Ligand (APO010) to which the graft is exposed during incubation prior to ApoGraft transplantation and HSCT, ranging from 10 ng/ml APO010 in Cohort 1, 25 ng/ml APO010 in Cohort 2, 50 ng/ml APO010 in Cohort 3 and 100 ng/ml APO010 in Cohort 4. APO010 is washed-out as part of the ApoGraft process and only trace amounts of APO010 are present in the final ApoGraft product

The study consists of a screening phase (subject and donor clinical assessment and screening tests), transplantation of ApoGraft, and a follow-up period of 180 days during and after hospitalization.

The study will progress from one cohort to the next based on an independent data safety monitoring board (DSMB) review and analysis of safety data

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hematological Malignancies
Intervention  ICMJE Biological: Allogeneic MPBC transplantation from matched related donor
Study Arms  ICMJE Experimental: ApoGraft
ApoGraft is a mobilized peripheral blood cell (MPBC) product derived from peripheral blood. There will be 4 cohorts, each differ in the amount of apoptotic mediator Fas Ligand (APO010) to which the graft is exposed during incubation prior to ApoGraft transplant, ranging from 10 ng/ml APO010 in Cohort 1, 25 ng/ml APO010 in Cohort 2, 50 ng/ml APO010 in Cohort 3, and 100 ng/ml APO010 in Cohort 4
Intervention: Biological: Allogeneic MPBC transplantation from matched related donor
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: July 7, 2016)
12
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2020
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Recipient/patient main inclusion criteria:

  1. Adult male or female subjects, 18-70 years of age.
  2. Subjects are eligible for allogeneic HLA-matched related HSCT for any hematological malignancies for which transplantation is appropriate with corresponding related donor. One of the following hemato-oncology disorders diagnosis is required:

    • Acute myelogenous leukemia (AML) and Acute lymphoblastic leukemia (ALL) in 1st or subsequent complete remission (CR)
    • Non-Hodgkin's disease (NHD) in CR by CT or PET/CT
    • Hodgkin's disease (HD) in 1st or subsequent CR by CT or PET/CT
    • Intermediate, High or Very High Risk Myelodysplastic syndrome (MDS) (IPSS-R criteria)
  3. The donor and recipient must have full match at the HLA A, B, C, DR and DQ loci.
  4. ECOG performance status score 0-1 at time of the screening visit.
  5. Subjects must have adequate organ function as defined in the study protocol
  6. Signed written informed consent to participate in the study.
  7. If female of childbearing potential, agree to use an acceptable method of birth control or be surgically sterile, and have a negative pregnancy test.

Donor main inclusion criteria:

  1. Adult male or female subjects, 18-65 years of age.
  2. Donor criteria according to standard WMDA criteria for donor selection. 3 Must have full match at the HLA A, B, C, DR and DQ loci with the recipient.

4. Signed written informed consent

Recipient/patient main exclusion criteria:

  1. Use of non-myeloabletive conditioning.
  2. Uncontrolled infections including sepsis, pneumonia with hypoxemia, persistent bacteremia, or meningitis within two weeks of the screening visit.
  3. Current known acute or chronic infection with HBV or HCV.
  4. Known human immunodeficiency virus (HIV) infection or AIDS.
  5. Subjects with severe or symptomatic restrictive or obstructive lung disease or respiratory failure requiring ventilator support.
  6. Subjects with other concurrent severe and/or uncontrolled medical condition, which could compromise participation in the study (i.e. active infection, uncontrolled diabetes, uncontrolled hypertension, congestive cardiac failure, unstable angina, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within six months and chronic liver or renal disease.
  7. Any form of substance abuse (including drug or alcohol abuse), psychiatric disorder or any chronic condition susceptible, in the opinion of the investigator, of interfering with the conduct of the study.
  8. Organ allograft or previous history of allogeneic stem cell transplantation.
  9. Pregnancy or lactation.

Donor main exclusion criteria:

  1. HIV, HBV or HCV positive subjects.
  2. Pregnant or lactating women.
  3. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Israel
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02828878
Other Study ID Numbers  ICMJE ApoGraft 01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Cellect Biotechnology
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Cellect Biotechnology
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Tsila Zuckerman, MD Rambam Hospital, Haifa, Israel
PRS Account Cellect Biotechnology
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP