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

NCT00524784 | Unknown Phase 1 DMC

• 1 other identifier: TLX-APO-101IL-HMO-CTIL
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Graft Versus Host Disease; Hematological Malignancies

Keywords

GVHD; HSCT; BMT; APOPTOTIC CELLS

Outcome Measures

Primary Outcomes (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.

  180 days

Secondary Outcomes (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

  180 days

Study Arms (1)

A

EXPERIMENTAL

Three subjects per cohort will be treated with ApoCell according to an escalating schedule of doses

Biological: ApoCell

Interventions

ApoCell BIOLOGICAL

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.

A

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).
• 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:

You may not qualify if:

• 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.
• 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.
• 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.

Sponsors & Collaborators

• Hadassah Medical Organization: lead

Study Sites (1)

Department of Bone Marrow Transplantation

Jerusalem, 91120, Israel

Location

Related Publications (1)

• 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.

  PMID: 24140121 DERIVED

MeSH Terms

Conditions

Graft vs Host Disease; Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Immune System Diseases; Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Reuven Or, Professor

  Hadassah Medical Organization

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2007
• First Posted: September 5, 2007
• Study Start: June 1, 2009
• Primary Completion: December 1, 2012
• Study Completion: April 1, 2016
• Last Updated: June 11, 2015

Record last verified: 2009-06

Locations

IL (1)