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

Phase 1

Completed

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

• Registration Number: NCT03483324
• Lead Sponsor: Angiocrine Bioscience

Brief 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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-03-23
• Study First Submitted QC: 2018-03-28
• Study First Posted: 2018-03-30
• Study Start: 2018-04-24
• Primary Completion: 2020-12-21
• Study Completion: 2022-01-31
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-26
• Last Update Posted: 2022-05-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental	Unmanipulated Umbilical Cord Blood (UCB)	Unmanipulated umbilical cord blood plus AB-110
Experimental	AB-110	Unmanipulated umbilical cord blood plus AB-110

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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 sustained donor-derived neutrophil engraftment	180 days
Disease Free Survival (DFS)	180 days
Time to neutrophil engraftment	42 days
Incidence of engraftment syndrome	28 days
Cumulative incidence of graft failure	180 days
Cumulative incidence of chronic GVHD	180 days
Cumulative incidence of transplant related mortality (TRM)	180 days
Overall survival (OS)	180 days
Time to lymphoid recovery	180 days

Trial Locations

Locations (3)

City of Hope Comprehensive Cancer Center; 🇺🇸 Duarte, California, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

University of Colorado Cancer Center University of Colorado Anschutz Medical Campus; 🇺🇸 Aurora, Colorado, United States