ApoGraft for the Prevention of Acute Graft Versus Host Disease in Haploidentical Hematopoietic Cell Transplant Recipients

NCT04006652 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 201911131
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Finding a donor remains a challenge for patients in need of an urgent hematopoietic stem cell transplantation (HSCT). The ability to obtain half matched stem cells from any family member represents a significant breakthrough in the field. Haploidentical haplo-HSCT is characterized by the nearly uniform and immediate availability of a donor and the availability of the donor for post-transplant cellular immunotherapy. However, haplo-HSCT has a high risk of Graft versus Host Disease (GvHD) and poor immune reconstitution when GvHD is prevented by all existing methods of vigorous ex vivo or in vivo T-cell depletion. Different treatment approaches are currently being explored to mitigate complications such as graft rejection, severe GvHD, and prolonged immune suppression. Novel experimental utilization of T regulatory cells, alloreactive natural killer (NK) cells, and other T cell subsets hold great promise. Cellect Biotherapeutics' platform technology, ApoGraft, is based on the findings that GvHD can be prevented by Fas receptor mediated selective depletion of T cell subsets, ex vivo. The investigators hypothesize that the use of ApoGrafts for haplo-HSCT will be safe, and reduce rates of GVHD without affecting Graft-versus-Leukemia (GvL).

Conditions

Acute Graft Versus Host Disease; Haploidentical Hematopoietic Stem Cell Transplant

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of ApoGraft as measured by adverse events related to ApoGraft product

  -The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting.

  From day 0 to 1 year post-transplantation of ApoGraft product

Secondary Outcomes (10)

• Cumulative incidence of graft failure

  35 days post haplo-HCT

• Treatment related mortality

  Through 1 year post-transplantation of ApoGraft product

• Time of neutrophil engraftment as determined by number of days for reaching first of 3 consecutive days with ANC ≥ 500/mm3

  35 days post haplo-HCT

• Rate of neutrophil engraftment as determined by number of days for reaching first of 3 consecutive days with ANC ≥ 500/mm3

  35 days post haplo-HCT

• Time of platelet engraftment determined by number of days for reaching first measurement of 3 consecutive measurements with platelets ≥ 20,000/mm3 in the absence of platelet administration during the prior 7 days

  35 days post haplo-HCT

Study Arms (2)

Recipient

EXPERIMENTAL

* Will undergo institutionally standard myeloablative or reduced intensity chemotherapy or chemoradiotherapy which will be administered at the discretion of the treating physician * Recipients will undergo a single fresh ApoGraft transplant as per standard clinical site guidelines

Drug: ApoGraft

Donor

NO INTERVENTION

-Donors will undergo apheresis from peripheral blood after daily G-CSF administration (for up to 5 days prior to Day -1)

Interventions

ApoGraft DRUG

ApoGraft is a cell based product, manufactured with mobilized peripheral blood.

Recipient

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult male or female subjects, 18-70 years of age.
• Availability of an HLA-haploidentical-HSCT related donor with a minimum match of 5/10 at the HLA A, B, C, DR and DQ loci.
• Hematologic malignancy in remission or controlled as below:
• Acute myelogenous leukemia (AML) and Acute lymphoblastic leukemia (ALL) in 1st or subsequent complete remission (CR)
• Non-Hodgkin's Lymphoma (NHL) in CR by CT or PET/CT
• Hodgkin's disease (HD) in 1st or subsequent CR by CT or PET/CT
• Intermediate or high risk Myelodysplastic syndrome (MDS) (IPSS-R criteria)
• ECOG performance status score 0-1 at time of the screening visit
• Cardiac left ventricular ejection fraction ≥ 40% in adults within 90 days of start of lymphodepleting chemotherapy
• Pulmonary function test with DLCO, FEV1 and FVC of ≥ 50% within 90 days of start of lymphodepleting chemotherapy.
• Oxygen saturation ≥ 90% on room air at screening visit.
• Subjects must have adequate organ function as defined below within 2 weeks of Day 0:
• AST (SGOT)/ALT (SGPT) ≤ 2.5 × upper limit of normal (ULN).
• Serum bilirubin \<3 mg/dL.
• Estimated creatinine clearance \>50

You may not qualify if:

• If a matched related donor is available and able to donate
• Participation in an interventional investigational trial within 30 days of Day 0.
• Subject suffering from any active or ongoing malignancy (other than the reason for HSCT) in the last 5 years prior to baseline; excluding basal cell carcinoma, in situ malignancy, low-risk prostate cancer, cervix cancer after curative therapy.
• Uncontrolled infections (bacterial, viral or fungal including sepsis, pneumonia with hypoxemia, persistent bacteremia, or meningitis within two weeks of the screening visit).
• Current known active 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, ventricular arrhythmias, and chronic liver or renal disease)
• History of any of the following within 12 months prior to screening: Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), unstable angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism.
• 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 transplant recipient.
• If female of childbearing potential, agree to use an acceptable method of birth control or be surgically sterile, and have a negative pregnancy test.
• Pregnancy or lactation
• Presence of donor-specific anti-HLA antibodies.
• Must not receive antithymocyte globulin as part of pre-transplant conditioning regimen, plan to receive a T-cell depleted product, or have planned donor leukocyte infusions post-transplant.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Cellect Biotechnology: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study Officials

• Mark Schroeder, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: The first three recipients will be treated in a sequential manner meaning that subjects will be transplanted with ApoGraft only after the engraftment of the previous subject has occurred.

Study Record Dates

• First Submitted: July 1, 2019
• First Posted: July 5, 2019
• Study Start: December 16, 2020
• Primary Completion: December 19, 2022
• Study Completion: December 19, 2022
• Last Updated: May 19, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)