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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03483324
• Other study ID #: AB-110-001
• Status: Completed
• Phase: Phase 1
• Start date: April 24, 2018
• Est. completion date: January 31, 2022

Study information

• Verified date: May 2022
• Source: Angiocrine Bioscience
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: January 31, 2022
• Est. primary completion date: December 21, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia in Remission
• Acute Myeloid Leukemia
• Hematologic Neoplasms
• Leukemia
• Myelodysplastic Syndromes
• Other Acute Leukemias
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• Unmanipulated Umbilical Cord Blood (UCB)
Human leukocyte antigen (HLA) matched umbilical cord blood
• AB-110
Expanded cord blood stem cells and engineered human endothelial cells

Locations

Country	Name	City	State
United States	University of Colorado Cancer Center University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Angiocrine Bioscience	California Institute for Regenerative Medicine (CIRM)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Late onset acute GVHD		720 days
Other	Chronic GVHD		720 days
Other	Quantitative recovery of T-cells and subsets		1 year
Other	Quantitative recovery of T-cells and subsets		2 years
Other	Transplant Related Mortality		1 year
Other	Transplant Related Mortality		2 years
Other	Recurrence of malignancy		1 year
Other	Recurrence of malignancy		2 years
Other	Overall survival		1 year
Other	Overall survival		2 years
Other	Disease free survival		1 year
Other	Disease free survival		2 years
Primary	Occurrence of adverse events grade 4 or grade 5 as assessed by CTCAEv4		24 hours
Primary	Graft failure defined as survival to day 42 without absolute neutrophil count greater than or equal to 500/mm3		42 days
Secondary	Time to neutrophil engraftment		42 days
Secondary	Cumulative incidence of sustained donor-derived neutrophil engraftment		42 days
Secondary	Cumulative incidence of sustained donor-derived neutrophil engraftment		100 days
Secondary	Cumulative incidence of sustained donor-derived neutrophil engraftment		180 days
Secondary	Incidence of engraftment syndrome		28 days
Secondary	Cumulative incidence of graft failure		43 days
Secondary	Cumulative incidence of graft failure		180 days
Secondary	Presence of post-transplant phenotype in hematopoietic cells of donor origin		180 days
Secondary	Cumulative incidence of grade II - IV acute graft versus host disease (aGVHD)		100 days
Secondary	Cumulative incidence of grade II - IV acute graft versus host disease (GVHD)		180 days
Secondary	Cumulative incidence of chronic GVHD		100 days
Secondary	Cumulative incidence of chronic GVHD		180 days
Secondary	Time to lymphoid recovery		180 days
Secondary	Cumulative incidence of transplant related mortality (TRM)		100 days
Secondary	Cumulative incidence of transplant related mortality (TRM)		180 days
Secondary	Overall survival (OS)		100 days
Secondary	Overall survival (OS)		180 days
Secondary	Disease Free Survival (DFS)		100 days
Secondary	Disease Free Survival (DFS)		180 days