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An Investigational Graft Processing Procedure (ApoGraft) for the Prevention of Acute Graft Versus Host Disease in Patients Undergoing Stem Cell Transplant

Trial Status: Active

This phase I trial studies the side effects of an investigational graft processing procedure (ApoGraft) in preventing acute graft versus host disease in patients undergoing a stem cell transplant. A stem cell is a type of cell found in the blood or bone marrow which helps form more blood cells. The purpose of a stem cell transplant is to use the stem cells from a healthy donor to replace the diseased bone marrow in the recipient. One of the side effects of a stem cell transplant is the development of graft versus host disease (GVHD). GVHD occurs when some of the cells from the donor attack the recipient’s tissues, resulting in mild, moderate, or even life-threatening side effects to the recipient’s skin, stomach, intestine, and liver. A haploidentical (half-matched related) stem cell transplant is a type of transplant that occurs when the person who needs a transplant can’t find a donor who exactly matches their tissue type (either among family members or through a matched unrelated donor). When no matched donor is available, haploidentical donors may be used. The purpose of this study is to see how well using ApoGraft in processing stem cells works to prevent or lessen the effects of GVHD while still effectively treating the disease in patients receiving a haploidentical stem cell transplant.

Inclusion Criteria

  • RECIPIENT INCLUSION:
  • 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 computed tomography (CT) or positron emission tomography (PET)/CT * Hodgkin’s disease (HD) in 1st or subsequent CR by CT or PET/CT * Intermediate or high risk myelodysplastic syndrome (MDS) (revised International Prognostic Scoring System [IPSS-R] criteria)
  • Eastern Cooperative Oncology Group (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 diffusion capacity of the lung for carbon monoxide (DLCO), forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) of >= 50% within 90 days of start of lymphodepleting chemotherapy
  • Oxygen saturation >= 90% on room air at screening visit
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X upper limit of normal (ULN) (within 2 weeks of day 0)
  • Serum bilirubin < 3 mg/dL (within 2 weeks of day 0)
  • Estimated creatinine clearance > 50 (within 2 weeks of day 0)
  • If female of childbearing potential, agree to use an acceptable method of birth control or be surgically sterile, and have a negative pregnancy test
  • Available HLA-haploidentical donor
  • Must be able to receive GvHD prophylaxis with tacrolimus, mycophenolate mofetil, and cyclophosphamide
  • Able to understand and willing to sign an Institutional Review Board (IRB) approved written informed consent document (or that of legally authorized representative, if applicable). Subjects requiring a guardian to sign informed consent will not be included
  • DONOR INCLUSION:
  • Adult male or female subjects, 18-65 years of age
  • Donor criteria according to standard National Marrow Donor Program (NMDP) criteria for donor selection. * Blood-related family member (sibling (full or half), offspring, parent, cousin, niece or nephew, aunt or uncle, or grandparent) * HLA-haploidentical donor/recipient match by at least low-resolution typing per institutional standards * In the investigator’s opinion, donor is in general good health, and medically able to tolerate leukapheresis required for harvesting hematopoietic stem cell (HSC)
  • Fit to receive granulocyte colony-stimulating factor (G-CSF) and donate peripheral blood stem cells
  • Able to sign written informed consent including consent for 2nd donation in the event of graft failure in the recipient

Exclusion Criteria

  • RECIPIENT EXCLUSION:
  • 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 hepatitis B virus (HBV) or hepatitis C virus (HCV)
  • Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (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
  • Pregnancy or lactation
  • Must not have undergone a prior allogeneic donor (related, unrelated, or cord) transplant. Prior autologous transplant is not exclusionary
  • 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
  • Immunosuppressive doses of steroids. Subjects with steroids for adrenal insufficiency will not be excluded
  • DONOR EXCLUSION:
  • HIV, HBV or HCV positive subjects within 30 days prior to day 0
  • Pregnant or lactating women
  • 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
  • Graft donation with less than 0.3% CD34+ cells

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: ACTIVE
Contact: Zhifu Xiang
Phone: 314-454-8304

PRIMARY OBJECTIVE:

I. To assess the safety and tolerability of ApoGraft product administered to subjects with hematologic malignancies undergoing human leukocyte antigen (HLA)-haploidentical allogeneic hematopoietic stem cell transplantation (HSCT).

SECONDARY OBJECTIVE:

I. To assess ApoGraft engraftment, acute graft versus host disease (aGvHD) incidence and transplant-related mortality.

OUTLINE:

Beginning 1 week before transplant, patients receive standard conditioning regimen per physician's direction. Patients receive ApoGraft intravenously (IV) within 4 hours of the completion of ApoGraft production on day 0. Patients then receive standard of care cyclophosphamide on days 3-4, tacrolimus orally (PO) or IV beginning on day 5 for at least 100 days before tapering, and mycophenolate mofetil PO on days 5-35.

At the completion of study treatment, patients are followed up to 1 year.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Siteman Cancer Center at Washington University

Principal Investigator
Zhifu Xiang

  • Primary ID 201911131
  • Secondary IDs NCI-2019-08881
  • Clinicaltrials.gov ID NCT04006652