Clinical trial NCT03483324: Trial of AB-110 in Adults With Hematologic Malignancies Undergoing Cord Blood Transplantation
Official title: A Phase 1 Open-Label, Multi-Center Trial of AB-110 in Adults With Hematologic Malignancies Undergoing Cord
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia in Remission
Myelodysplastic Syndromes
Other Acute Leukemias
Lead sponsor: Angiocrine Bioscience
Sponsor class: INDUSTRY
Collaborators: name: California Institute for Regenerative Medicine (CIRM)
First posted: 2018-03-30
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Occurrence of adverse events grade 4 or grade 5 as assessed by CTCAEv4
timeFrame: 24 hours
measure: Graft failure defined as survival to day 42 without absolute neutrophil count greater than or equal to 500/mm3
timeFrame: 42 days
Secondary outcomes:
measure: Time to neutrophil engraftment
timeFrame: 42 days
measure: Cumulative incidence of sustained donor-derived neutrophil engraftment
timeFrame: 42 days
measure: Cumulative incidence of sustained donor-derived neutrophil engraftment
timeFrame: 100 days
measure: Cumulative incidence of sustained donor-derived neutrophil engraftment
timeFrame: 180 days
measure: Incidence of engraftment syndrome
timeFrame: 28 days
measure: Cumulative incidence of graft failure
timeFrame: 43 days
measure: Cumulative incidence of graft failure
timeFrame: 180 days
measure: Presence of post-transplant phenotype in hematopoietic cells of donor origin
timeFrame: 180 days
measure: Cumulative incidence of grade II - IV acute graft versus host disease (aGVHD)
timeFrame: 100 days
measure: Cumulative incidence of grade II - IV acute graft versus host disease (GVHD)
timeFrame: 180 days
measure: Cumulative incidence of chronic GVHD
timeFrame: 100 days
measure: Cumulative incidence of chronic GVHD
timeFrame: 180 days
measure: Time to lymphoid recovery
timeFrame: 180 days
measure: Cumulative incidence of transplant related mortality (TRM)
timeFrame: 100 days
measure: Cumulative incidence of transplant related mortality (TRM)
timeFrame: 180 days
measure: Overall survival (OS)
timeFrame: 100 days
measure: Overall survival (OS)
timeFrame: 180 days
measure: Disease Free Survival (DFS)
timeFrame: 100 days
measure: Disease Free Survival (DFS)
timeFrame: 180 days
Other outcomes:
measure: Late onset acute GVHD
timeFrame: 720 days
measure: Chronic GVHD
timeFrame: 720 days
measure: Quantitative recovery of T-cells and subsets
timeFrame: 1 year
measure: Quantitative recovery of T-cells and subsets
timeFrame: 2 years
measure: Transplant Related Mortality
timeFrame: 1 year
measure: Transplant Related Mortality
timeFrame: 2 years
measure: Recurrence of malignancy
timeFrame: 1 year
measure: Recurrence of malignancy
timeFrame: 2 years
measure: Overall survival
timeFrame: 1 year
measure: Overall survival
timeFrame: 2 years
measure: Disease free survival
timeFrame: 1 year
measure: Disease free survival
timeFrame: 2 years
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center University of Colorado Anschutz Medical Campus
state: Colorado
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Angiocrine Bioscience
name: Paul Finnegan, MD
role: STUDY_DIRECTOR
References: