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Graft Versus Host DiseasePhase 1/2NCT00524784

Open-Label Study Designed to Evaluate the Safety and Preliminary Efficacy of ApoCell for the Prevention of Acute GvHD

A Phase 1/2 study testing ApoCell in people with Graft Versus Host Disease and Hematological Malignancies, run by Hadassah Medical Organization at 1 site in Israel.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Bone marrow transplantation (BMT) has revolutionized the treatment of hematopoietic malignancies.Unfortunately, graft versus host disease (GvHD) remains a major toxicity that greatly limits the application and efficacy of BMT.Current standard prophylaxis and therapy for acute GvHD include mainly the use of… Read more about this study

Who is it for?
Ages 18 to 60 years
What is being tested?
ApoCell
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteIsrael
Study dates
Jun 2009to Apr 2016
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Adult male or female subjects, 18-60 years of age, inclusive, at the time of screening visit weighing at least 40 kg.
  • Subjects are eligible for allogeneic sibling HLA-matched HSCT for any disease for which transplantation is appropriate except progressive or poorly controlled malignancies. Only one of the following malignancies should be present:
  • Acute lymphoblastic leukemia or acute myeloid or undifferentiated or biphenotypic, leukemia, in complete remission or beyond but with ≤10% blasts in bone marrow.
  • Acute myeloid leukemia in complete remission if it has evolved from myelodysplastic syndrome (MDS) (there should be documented diagnosis of MDS at least 3 months prior to diagnosis of acute myeloid leukemia).
  • Myelodysplastic syndromes - MDS
  • Therapy related MDS (irrespective of IPSS).
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  • Chronic myeloid leukemia (CML) chronic phase-1 (imatinib failures, imatinib intolerance), or any CML beyond first chronic phase.
  • Multiple Myeloma.
  • The donor and recipient must have at least a 7/8 HLA match at the HLA A, B, C, and DR loci.
  • Life expectancy of at least 6 months at the time of the baseline visit.
  • Karnofsky performance status score ≥ 80% at time of the screening visit.
  • Cardiac left ventricular ejection fraction ≥ 40% in adults within 4 weeks of initiation of conditioning; required if prior anthracycline exposure or history of cardiac disease.
  • Pulmonary function test with DLCO, FEV1 and FVC of ≥ 60%.
  • Oxygen saturation ≥ 90% on room air.
  • Subjects must have normal organ function as defined below:
  • AST (SGOT)/ALT (SGPT) ≤ 2.5 x upper limit of normal (ULN).
  • Serum creatinine <2.5 mg/dL.
  • Serum bilirubin <3 mg/dL.
  • Coagulation markers - PT and PTT within normal limits.
  • Signed written informed consent to participate in the study independently by subject. Subjects requiring a guardian to sign informed consent will not be included.
  • Ability to comply with the requirements of the study.
  • If female, agree to use an acceptable method of birth control or be surgically sterile, and have a negative pregnancy test regardless of child-bearing potential.
  • Male or female donors, 18 - 65 years of age, inclusive.
  • The donor and recipient must have at least a 7/8 HLA match at the HLA A, B, C, and DR loci.
  • Above 40 kg.
  • Not pregnant and negative pregnancy test.
  • Serum creatinine < 2.5 mg/dL.
  • Oxygen saturation ≥ 90% on room air.
  • No severe or symptomatic restrictive or obstructive lung disease or respiratory failure requiring ventilator support.
  • No uncontrolled hypertension or congestive heart failure, active angina pectoris requiring the use of nitrates, or major ventricular arrhythmia or cardiac failure requiring active treatment.
  • Not HIV-1/2 or HTLV I/II seropositive or evidence of acute CMV infection.
  • Not seropositive for Hepatitis B or C.
  • Not positive for syphilis.
  • No known bone marrow disease.
  • No significant organ dysfunction.
  • No acute infectious disease within two weeks of donation.
  • Willingness to donate hematopoietic blood mononuclear cells for the generation of ApoCell more than one time if required and in addition to the donation for the HSCT.
  • Ability to provide written informed consent and comply with study requirements.

Who cannot join

  • Participation in an investigational trial within 30 days of the screening visit.
  • Have progressive or poorly controlled malignancies.
  • T-cell depleted allograft.
  • Uncontrolled infections including sepsis, pneumonia with hypoxemia, persistent bacteremia, or meningitis within two weeks of the screening visit.
  • Current known acute or chronic infection with HBV or HCV.
  • Known human immunodeficiency virus (HIV) infection or AIDS.
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  • Subjects with severe or symptomatic restrictive or obstructive lung disease or respiratory failure requiring ventilator support.
  • 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, chronic liver or renal disease, active upper gastrointestinal tract ulceration).
  • Any chronic or acute condition susceptible of interfering with the evaluation of investigational product effect.
  • 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.
  • Organ allograft or previous history of allogeneic stem cell transplantation.
  • For all women: A positive pregnancy test at screening or breast-feeding.
  • Subjects who are likely to be non-compliant or uncooperative during the study.

Trial locations and contacts

1 site in 1 country.

Israel1 site

  • Department of Bone Marrow Transplantation

    Jerusalem, 91120

Other trials in Israel

About this study

Official title: Phase 1/2a, Multicenter, Open-Label Study Designed to Evaluate the Safety, Tolerability and Preliminary Efficacy of ApoCell Administration, a Donor Apoptotic Cell-Based Product, for the Prevention of Acute Graft Versus Host Disease (GvHD) in Subjects With Hematologic Malignancies Undergoing Allogeneic Sibling HLA-Matched Hematopoietic Stem Cell Transplantation (HSCT)

Bone marrow transplantation (BMT) has revolutionized the treatment of hematopoietic malignancies.Unfortunately, graft versus host disease (GvHD) remains a major toxicity that greatly limits the application and efficacy of BMT.Current standard prophylaxis and therapy for acute GvHD include mainly the use of immunosuppressive drugs that help less than 50% of the patients and are associated with increased infection risk. ApoCell treatment is anticipated to be a prophylactic measure for acute GvHD by inducing tolerance in the donor effector cells, leading to a potentially significant decrease in GVHD.

Read the detailed description

Allogeneic hematopoietic stem-cell transplantation (HSCT) has revolutionized the treatment of hematopoietic malignancies, inherited hematopoietic disorders, aplastic anemia, and other severe diseases. Unfortunately, graft versus host disease (GvHD) remains a major toxicity that greatly limits the application and efficacy of allogeneic HSCT, occurring commonly after the procedure and affecting 30 to 80% of patients. Acute GvHD occurs within 100 days in up to 50% of allogeneic HLA-matched HSCT recipients despite prophylactic immunosuppressive drugs.

The most efficient treatment for GvHD prevention is T cell depletion. However, most clinicians avoid that modality due to the crucial effect of T cells in prevention of tumor relapse. Current standard prophylaxis and therapy for acute GvHD include mainly the use of immunosuppressive drugs that help less than 50% of the patients and are associated with increased infection risk. New strategies of GvHD prophylaxis are examined and this study uses a physiological strategy of antigen presenting cell (APC) tolerance induction that will modulate effector cells either directly or via T regulatory cells.

ApoCell treatment is anticipated to be a prophylactic measure for acute GvHD by inducing tolerance in the donor effector cells, leading to a potentially significant decrease in the immune response of the donor cells against the recipient. The effects of apoptotic cells on preventing GvHD may involve the following mechanisms: inhibit pro-inflammatory cytokine production, promote anti-inflammatory cytokines production, induce tolarogenic APCs, decrease ability to stimulate T-cell responses, delete CD8 T-effector cells, induce regulatory T-cells, and inhibit response to inflammatory cytokines and LPS.

Tolarex Ltd. is proposing a novel cell-based approach of donor apoptotic cells treatment, ApoCell, for a Phase I-IIa study of patients undergoing sibling HSCT with high risk of developing acute GvHD. The ApoCell product is composed of HLA-matched donor mononuclear enriched leukocytes in the form of liquid suspension that will be injected intravenously to the patient 24 hours prior to HSCT. The ApoCell suspension contains at least 55% of early apoptotic cells. The cell suspension is prepared under cGMP conditions with PBS solution within 8 hours prior to intravenous injection and should be stored at 2-8oC until administered.

Being tested
ApoCell
Keywords
GVHD, HSCT, BMT, APOPTOTIC CELLS
Medical subject headings
Graft vs Host Disease, Hematologic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ApoCellBiological

    Three subjects per cohort will be treated with ApoCell according to an escalating schedule of doses starting at a single dose of 35 million apoptotic cells/kg in the first cohort of three subjects. Unless a DLT is experienced by subjects in a given cohort, the dose in the subsequent cohort will be increased by two-fold. The second cohort will receive 70 millions cells/kg, and the third cohort 140 millions cells/kg. The final fourth cohort will receive 210 millions cells/kg.

Study groups in NCT00524784
Study groupRoleWhat they receive
AExperimentalThree subjects per cohort will be treated with ApoCell according to an escalating schedule of doses
Receives: Biological: ApoCell

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Determine the safety profile and tolerability [dose limiting toxicity (DLT)] of ascending doses of ApoCell in subjects undergoing allogeneic sibling HLA-matched HSCT within 180 days post-transplantation.

    Measured: 180 days

Secondary outcomes (1)

  1. *Determine the success rate for HSC engraftment and time to successful engraftment. *Describe the rates and grade of acute GvHD following ApoCell infusion. *Determine the success rate for HSC engraftment and time to successful engraftment. *Determine

    Measured: 180 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Sep 2007 (estimated)
  2. Study startJun 2009
  3. Primary completionDec 2012
  4. Study completionApr 2016 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Prevention
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00524784
Sponsor's protocol ID
TLX-APO-101IL-HMO-CTIL
Status last verified
Jun 2009
First submitted
4 Sep 2007
Last updated
11 Jun 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • Mevorach D, Zuckerman T, Reiner I, Shimoni A, Samuel S, Nagler A, Rowe JM, Or R. Single infusion of donor mononuclear early apoptotic cells as prophylaxis for graft-versus-host disease in myeloablative HLA-matched allogeneic bone marrow transplantation: a phase I/IIa clinical trial. Biol Blood Marrow Transplant. 2014 Jan;20(1):58-65. doi: 10.1016/j.bbmt.2013.10.010. Epub 2013 Oct 15.

    PubMed 24140121

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ApoCell in people with Graft Versus Host Disease and Hematological Malignancies, run by Hadassah Medical Organization at 1 site in Israel.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 38 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 11 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determine the safety profile and tolerability [dose limiting toxicity (DLT)] of ascending doses of ApoCell in subjects undergoing allogeneic sibling HLA-matched HSCT within 180 days post-transplantation. (time frame: 180 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00524784, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2015.

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