Trial of AB-110 in Adults With Hematologic Malignancies Undergoing Cord Blood Transplantation

Study Overview
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Brief Summary
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A phase 1b, open label, multi-center trial of AB-110 in adults with hematologic malignancies, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplasia (MDS) undergoing cord blood transplantation. Subjects will receive unmanipulated cord blood (UCB) and AB-110 expanded CD34 enriched hematopoietic progenitor cells (HSPC).

Official Title
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A Phase 1 Open-Label, Multi-Center Trial of AB-110 in Adults With Hematologic Malignancies Undergoing Cord

Conditions
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Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia in Remission, Myelodysplastic Syndromes, Other Acute Leukemias

Intervention / Treatment
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* Biological: Unmanipulated Umbilical Cord Blood (UCB)
* Biological: AB-110


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have received some immunosuppressive chemotherapy in the preceding 3 months. Acute myelogenous leukemia (AML): Complete first remission (CR1) at high risk for relapse Complete second remission (CR2). No documented myelofibrosis at screening marrow biopsy Acute lymphoblastic leukemia (ALL): Complete first remission (CR1) at high risk for relapse Complete second remission (CR2). Other acute leukemias that are of ambiguous lineage or of other types Any acute leukemia with marrow aplasia or without adequate count recovery. Myelodysplastic Syndrome (MDS) Karnofsky score > 70 %. Calculated creatinine clearance > 60 ml/min. Bilirubin < 1.5 mg/dL, ALT < 3 x upper limit of normal Pulmonary function (FVC, FEV1 and corrected DLCO) > 50% predicted. Left ventricular ejection fraction > 50%. Albumin > 3.0 g/dL. Negative antiviral serology: Negative human immunodeficiency virus (HIV) antibody. Negative human T-lymphotropic virus (HTLV)-1 and 2 antibodies. Negative hepatitis B surface antigen (HBsAg) and undetectable hepatitis B virus (HBV) DNA Negative hepatitis C virus (HCV) antibody or negative HCV ribonucleic acid (RNA) For female subjects of childbearing potential: A negative serum pregnancy test Willing to use contraception throughout the study period. Male subjects must be willing to use a recommended method of contraception throughout the study period, and to refrain from sperm donation throughout the study period. Two appropriate CB units identified for the subject. In the judgment of the investigator, participation in the protocol offers an acceptable benefit-to-risk ratio when considering current disease status, medical condition, and the potential benefits and risks of alternative treatments for the subject's cancer. Willingness and ability to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions. Evidence of a signed informed written consent Exclusion Criteria: Pregnancy or breastfeeding. Current active, uncontrolled bacterial, viral, or fungal infection Prior allogeneic or autologous HCT at any time. Active malignancy other than the one for which AB-110 transplant is being performed within 12 months of enrollment. Any identified and available 10/10 HLA-matched related donor or 10/10 HLA-matched unrelated donor. Have evidence of recipient donor specific anti-HLA antibodies. Active central nervous system (CNS) disease at time of screening. Documented allergy to DMSO, mouse or bovine proteins, or iron. Subject has other conditions that in the opinion of the investigator would place the subject at increased risk for toxicity by participation in the study. Psychiatric condition making the patient unlikely to comply with protocol therapy, required tests and follow-up.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>Unmanipulated umbilical cord blood plus AB-110 | Biological: Unmanipulated Umbilical Cord Blood (UCB)<br>* Human leukocyte antigen (HLA) matched umbilical cord blood<br>Biological: AB-110<br>* Expanded cord blood stem cells and engineered human endothelial cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of adverse events grade 4 or grade 5 as assessed by CTCAEv4 |  | 24 hours | 
| Graft failure defined as survival to day 42 without absolute neutrophil count greater than or equal to 500/mm3 |  | 42 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to neutrophil engraftment |  | 42 days | 
| Cumulative incidence of sustained donor-derived neutrophil engraftment |  | 42 days | 
| Cumulative incidence of sustained donor-derived neutrophil engraftment |  | 100 days | 
| Cumulative incidence of sustained donor-derived neutrophil engraftment |  | 180 days | 
| Incidence of engraftment syndrome |  | 28 days | 
| Cumulative incidence of graft failure |  | 43 days | 
| Cumulative incidence of graft failure |  | 180 days | 
| Presence of post-transplant phenotype in hematopoietic cells of donor origin |  | 180 days | 
| Cumulative incidence of grade II - IV acute graft versus host disease (aGVHD) |  | 100 days | 
| Cumulative incidence of grade II - IV acute graft versus host disease (GVHD) |  | 180 days | 
| Cumulative incidence of chronic GVHD |  | 100 days | 
| Cumulative incidence of chronic GVHD |  | 180 days | 
| Time to lymphoid recovery |  | 180 days | 
| Cumulative incidence of transplant related mortality (TRM) |  | 100 days | 
| Cumulative incidence of transplant related mortality (TRM) |  | 180 days | 
| Overall survival (OS) |  | 100 days | 
| Overall survival (OS) |  | 180 days | 
| Disease Free Survival (DFS) |  | 100 days | 
| Disease Free Survival (DFS) |  | 180 days |