Study of Allogeneic Umbilical Cord Blood Infusion for Adults With Ischemic Stroke

NCT03004976 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: Pro00077580
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 6

Brief Summary

The primary objective of this study is to determine the efficacy of a single intravenous infusion of unrelated donor umbilical cord blood (UCB) for improving functional outcomes in patients with ischemic stroke. Eligible subjects will receive an intravenous infusion of UCB or placebo 3-10 days following stroke. Subjects will not receive immunosuppressive or myeloablative medications prior to the infusion. Subjects will be followed for one year post infusion for safety and efficacy. Assessments will examine safety and tolerability of the infusion, change in neurological symptoms, change in quality of life, and emotional and cognitive status. Assessments will occur at 24 hours post infusion, and at 30, 90, 180 and 365 days post infusion.

Conditions

Stroke; Stroke, Acute; Brain Injury, Acute

Keywords

hematopoietic stem cells; umbilical cord blood; stroke; ischemic stroke

Outcome Measures

Primary Outcomes (1)

• Shift in Modified Rankin Scale (mRS)

  The Modified Rankin Score (mRS) is a disability scale with possible scores ranging from 0 to 6, where 6 = death. Since a shift downward in the mRS scale is considered a clinical improvement, shift scores are calculated from baseline to ensure that, for hypothesis testing purposes, larger shift values represent more clinically desirable outcomes.

  baseline to 3 months post infusion

Secondary Outcomes (23)

• Number of Infusion Reactions

  up to 1 year post infusion

• Number of Product-related Infections

  up to 1 year post infusion

• Number of Alloimmunization Events

  up to 1 year post infusion

• Number of Graft vs. Host Disease Events

  up to 1 year post infusion

• Number of Study Related and Unexpected Adverse Events (AEs)

  up to 1 year post infusion

Study Arms (2)

Umbilical Cord Blood

EXPERIMENTAL

A single intravenous infusion of umbilical cord blood within 3-10 days following stroke.

Biological: Umbilical Cord Blood

Placebo

PLACEBO COMPARATOR

A single intravenous infusion of diluent with the same appearance and odor as a cord blood unit within 3-10 days following stroke.

Other: Placebo

Interventions

Umbilical Cord Blood BIOLOGICAL

Umbilical cord blood will be infused intravenously through a peripheral IV line after premedication with diphenhydramine, hydrocortisone, and acetaminophen. Units will be from a public cord blood bank with selection based on blood type, race, and the number of cells in the pre cryopreservation product, targeting a dose range of 0.5 to 5 x 10\^7 TNCC/kg.

Also known as: cord blood, hematopoietic stem cells

Umbilical Cord Blood

Placebo OTHER

The placebo product will be acellular and will consist of tissue culture medium 199 (TC-199 \[pink\]) with 1% dimethyl sulfoxide (DMSO), which are standard components in cellular products. The volume of placebo product will be 50 mL, which is in the range of a typical UCB unit that has been washed and thawed after cryopreservation. Infusion and premedication procedures will be the same as those conducted for the umbilical cord blood arm.

Placebo

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old
• Recent, acute, cortical, hemispheric, ischemic stroke in the MCA (middle cerebral artery) distribution without a clinically significant midline shift as detected by MRI as a DWI (diffusion-weighted imaging) abnormality. If unable to obtain a MRI scan, patients may be included if there is clear evidence of ischemic cortical involvement in the MCA distribution demonstrated by computed tomography and a clinical exam consistent with cortical involvement.
• NIHSS 6-15 (R) and 6-20 (L) at the time of informed consent. Subjects with a \>4-point increase of NIHSS from time of consent (worsening of score) will not be eligible for infusion.
• Subjects must have a platelet count \>100,000/uL, hemoglobin \>8gm/dL, absolute lymphocyte count (ALC) ≥ 1200 for African American patients and ≥1500 for all other racial-ethnic groups, and WBC (white blood cell) count \>2,500/uL OR Historical pre-stroke value of ALC ≥ 1200 for African American and ≥1500 for all other racial-ethnic groups within 6 months of stroke
• And- a post stroke ALC value of ≥ 1000, platelet count \>100,000/uL, hemoglobin \>8gm/dL and WBC \>2,500/uL.
• Subjects who received tPA (Tissue plasminogen Activator) or underwent endovascular reperfusion may be included in the study
• Able to provide consent to study or consent is obtained from the patient's legal representative
• Subjects of childbearing potential must practice effective contraception during the study, and be willing to continue contraception for at least 6 months after intervention so that, in the opinion of the Investigator, they will not become pregnant during the course of the study
• Is a good candidate for the trial, in the opinion of the Investigator
• Agrees to participate in follow-up visits
• ABO/Rh and race matched CBU(s) with a minimum of 0.5 x 10\^7 TNCC/kg based on the pre-cryopreservation TNCC is available for infusion
• Has not had a disease or therapy that would compromise current immune function.
• Has a serum creatinine ≤2 mg/dL OR Glomerular Filtration Rate (GFR) ≥30mL/min

You may not qualify if:

• An individual is ineligible to participate if any of the following apply:
• Medical history of neurological or orthopedic pathology with a deficit as a consequence that results in a modified Rankin Scale \>1 before stroke or has a pre existing cognitive deficit
• Clinically significant and/or symptomatic hemorrhage associated with stroke
• Evidence of significant midline shift as assessed by CT or MRI who are felt to be at high risk for neurological decompensation or need for decompressive hemicraniectomy due to hemispheric edema
• New intracranial hemorrhage, edema, or mass effect that may place patient at increased risk for secondary deterioration when assessed prior to infusion
• Hypotension as defined as the need for IV pressor support of SBP (systolic blood pressure) \<90
• Isolated brain stem stroke
• Pure lacunar stroke
• At time of consent, patients who are mechanically ventilated or, at the investigator's discretion are felt to be likely to need mechanical ventilation are excluded.
• Requires a craniotomy
• Serious psychiatric or neurological disease which could alter evaluation on functional or cognitive scales
• Active systemic infection that is felt, at the discretion of the Investigator, to place the patient at increased risk for participation in this study
• Documentation of human immunodeficiency virus positive (HIV+) status in the medical record
• Active malignancy within 3 years prior to the start of screening excluding skin cancers other than melanoma
• Known hypercoagulable state or coagulopathy deficiencies such as Factor V Leiden, Antiphospholipid Syndrome (APC), Protein C, Protein S, anticardiolipin antibody, phospholipid syndrome or Sickle Cell Disease

Sponsors & Collaborators

• Joanne Kurtzberg, MD: lead
• The Marcus Foundation: collaborator
• Emory University: collaborator
• M.D. Anderson Cancer Center: collaborator

Study Sites (6)

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

University of Florida Health Shands Hospital

Gainesville, Florida, 32610, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30303, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Houston Methodist

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Stroke; Brain Injuries; Ischemic Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Results Point of Contact

• Title: Emily Poehlein, MB
• Organization: Duke University

emily.poehlein@duke.edu

919-668-8473

Study Officials

• Joanne Kurtzberg, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Robertson Clinical and Translational Cell Therapy Program

Study Record Dates

• First Submitted: November 30, 2016
• First Posted: December 29, 2016
• Study Start: March 14, 2017
• Primary Completion: July 17, 2020
• Study Completion: March 27, 2021
• Last Updated: December 6, 2022
• Results First Posted: September 23, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)