Study of Allogeneic Umbilical Cord Blood Infusion for Adults With Ischemic Stroke
Study of Allogeneic Umbilical Cord Blood Infusion for Adults With Ischemic Stroke
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.
This is a multicenter, placebo controlled, randomized, double blinded Phase 2 study in 100
 subjects 18-90 years of age who have sustained a recent ischemic stroke. Potential subjects
 can be screened and consented the day of their stroke (Day 1). Treatment with umbilical cord
 blood (UCB) cells or placebo will be administered intravenously as a single infusion as early
 as 3 days but no later than 10 days after the patient's stroke. UCB units will be selected
 from an accredited U.S. public cord bank based on blood type, race and a targeted cell dose
 ranging between 0.5 to 5 x 10^7 total nucleated cell count (TNCC)/kg. Study subjects will not
 receive immunosuppressive or myeloablative medications prior to infusion of the cord blood or
 placebo.

 All subjects, families and medical staff will be blinded to treatment arm. When a subject is
 randomized to study drug at a clinical site without a cord blood bank, the selected cord
 blood units (CBU) will be shipped frozen overnight to the site. Once selected and available
 on site, each CBU will be thawed, washed, tested, released and infused intravenously using
 common standard operating procedures (SOPs) at all sites. For subjects randomized to placebo,
 a diluent with the same appearance and odor as a CBU will be prepared.

 Patients will have baseline magnetic resonance imaging (MRI) and will be assessed at 1, 3, 6,
 and 12 months for functional outcomes. All patients will receive standard of care therapy
 while enrolled in this study and all subjects will be strongly encouraged to participate in
 rehabilitative therapy.

 The primary objective of the study is to determine, in a randomized, placebo controlled
 trial, the efficacy of a single intravenous (IV) infusion of unrelated donor UCB for
 improving functional outcomes in patients with ischemic stroke. The secondary objectives are
 as follows:

 1. To describe the safety and tolerability of a single IV infusion of unrelated donor UCB
 in patients with ischemic stroke

 2. To evaluate the efficacy of a single IV infusion of unrelated donor UCB for improvement
 of neurological symptoms following ischemic stroke

 3. To evaluate the efficacy of a single IV infusion of unrelated donor UCB for improvement
 in quality of life and emotional and cognitive status in patients with ischemic stroke
Inclusion Criteria:

 1. 18-90 years old

 2. Recent, acute, cortical, hemispheric, ischemic stroke in the MCA distribution without
 a clinically significant midline shift as detected by MRI as a DWI 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.

 3. 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.

 4. 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 >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.

 5. Subjects who received tPA or underwent endovascular reperfusion may be included in the
 study

 6. Able to provide consent to study or consent is obtained from the patient's legal
 representative

 7. 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

 8. Is a good candidate for the trial, in the opinion of the Investigator

 9. Agrees to participate in follow-up visits

 10. 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

 11. Has not had a disease or therapy that would compromise current immune function.

 12. Has a serum creatinine ≤2 mg/dL OR Glomerular Filtration Rate (GFR) ≥30mL/min

 Exclusion Criteria:

 An individual is ineligible to participate if any of the following apply:

 Exclusionary Medical Conditions:

 1. 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

 2. Clinically significant and/or symptomatic hemorrhage associated with stroke

 3. 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

 4. New intracranial hemorrhage, edema, or mass effect that may place patient at increased
 risk for secondary deterioration when assessed prior to infusion

 5. Hypotension as defined as the need for IV pressor support of SBP <90

 6. Isolated brain stem stroke

 7. Pure lacunar stroke

 8. 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.

 9. Requires a craniotomy

 10. Serious psychiatric or neurological disease which could alter evaluation on functional
 or cognitive scales

 11. Active systemic infection that is felt, at the discretion of the Investigator, to
 place the patient at increased risk for participation in this study

 12. Documentation of human immunodeficiency virus positive (HIV+) status in the medical
 record

 13. Active malignancy within 3 years prior to the start of screening excluding skin
 cancers other than melanoma

 14. 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

 15. History of or currently active autoimmune disease, or current immunomodulatory therapy
 or a recipient of immunomodulatory therapy in the past year.

 16. Concurrent illness or condition that in the opinion of the Investigator might
 interfere with treatment or evaluation of safety

 17. Current or recent history of alcohol or drug abuse, or stroke associated with drug
 abuse that Investigator feels may impair therapy or assessments

 18. Pregnant as documented by blood test

 Prohibited Concomitant or Prior Therapies

 1. Patients currently receiving immunosuppressant drugs, not including glucocorticoid
 taper, topical/inhaled glucocorticoids

 2. History of prior transfusion reaction

 3. Currently on dialysis

 4. Recipient of bone marrow or organ transplant

 5. Hepatic insufficiency (bilirubin >2.5mg/dL or transaminases >5x the ULN) Patients with
 Gilberts syndrome are eligible for study enrollment if other liver function tests are
 normal, regardless of bilirubin level

 6. Previous or current treatment with angiogenic growth factors, cytokines, gene or stem
 cell therapy

 7. Participating in another interventional clinical trial of an investigational therapy
 within 30 days of consent.

 Other Exclusion Criteria

 1. Pregnant or lactating women

 2. Unable or unwilling to be evaluated for follow-up visits