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

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

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).

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes; Acute Lymphoblastic Leukemia in Remission; Other Acute Leukemias
• Intervention / Treatment: Biological: Unmanipulated Umbilical Cord Blood (UCB); Biological: AB-110

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center University of Colorado Anschutz Medical Campus
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have received some immunosuppressive chemotherapy in the preceding 3 months.

• Acute myelogenous leukemia (AML):

  1. Complete first remission (CR1) at high risk for relapse
  2. Complete second remission (CR2).
  3. No documented myelofibrosis at screening marrow biopsy

• Acute lymphoblastic leukemia (ALL):

  1. Complete first remission (CR1) at high risk for relapse
  2. 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:

  1. A negative serum pregnancy test
  2. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Other Outcome Measures

Outcome Measure	Time Frame
Overall survival	1 year
Disease free survival	2 years
Overall survival	2 years
Disease free survival	1 year
Late onset acute GVHD	720 days
Chronic GVHD	720 days
Quantitative recovery of T-cells and subsets	1 year
Quantitative recovery of T-cells and subsets	2 years
Transplant Related Mortality	1 year
Transplant Related Mortality	2 years
Recurrence of malignancy	1 year
Recurrence of malignancy	2 years

Collaborators and Investigators

• Sponsor: Angiocrine Bioscience
• Collaborators: California Institute for Regenerative Medicine (CIRM)

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 24, 2018
• Primary Completion (ACTUAL): December 21, 2020
• Study Completion (ACTUAL): January 31, 2022

Study Registration Dates

• First Submitted: March 23, 2018
• First Submitted That Met QC Criteria: March 28, 2018
• First Posted (ACTUAL): March 30, 2018

Study Record Updates

• Last Update Posted (ACTUAL): May 31, 2022
• Last Update Submitted That Met QC Criteria: May 26, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Leukemia, Lymphoid; Myelodysplastic Syndromes; Hematologic Neoplasms; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: AB-110-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No