Phase 2 Study of Allogeneic Umbilical Cord Blood Infusion for Adults With Ischemic Stroke - CoBIS 2
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Stroke
- Sponsor
- Joanne Kurtzberg, MD
- Enrollment
- 79
- Locations
- 6
- Primary Endpoint
- Shift in Modified Rankin Scale (mRS)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Detailed Description
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
Investigators
Joanne Kurtzberg, MD
Director, Robertson Clinical and Translational Cell Therapy Program
Duke University
Eligibility Criteria
Inclusion Criteria
- •18-90 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
Exclusion Criteria
- •An individual is ineligible to participate if any of the following apply:
- •Exclusionary Medical Conditions:
- •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.
Outcomes
Primary Outcomes
Shift in Modified Rankin Scale (mRS)
Time Frame: baseline to 3 months post infusion
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.
Secondary Outcomes
- Mortality(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)
- Shift in Modified Rankin Scale (mRS) From Baseline to 30 Days Post Infusion(baseline to 30 days post infusion)
- Controlled Oral Word Association Test (COWAT) Score at 90 Days Post Infusion(90 days post infusion)
- Telephone Interview for Cognitive Status (TICS) Total Score at 30 Days Post Infusion(30 days post infusion)
- Oral Symbol Digit Modalities Test (SDMT) Score at 90 Days Post Infusion(90 days post infusion)
- Number of Infusion Reactions(up to 1 year post infusion)
- Number of Product-related Infections(up to 1 year post infusion)
- Number of Participants With Functional Independence(90 days post infusion)
- Barthel Index (BI) Score at 90 Days(90 days post infusion)
- Hopkins Verbal Learning Test-Revised (HVLT-R) Score at 90 Days Post Infusion(90 days post infusion)
- Telephone Interview for Cognitive Status (TICS) Total Score at 1 Year Post Infusion(1 year post infusion)
- Shift in Modified Rankin Scale (mRS) From Baseline to 180 Days Post Infusion(baseline to 180 days post infusion)
- Stroke Impact Scale-16 (SIS-16) Score at 90 Days(90 days post infusion)
- Trail Making Test Score at 90 Days Post Infusion (Trail A)(90 days post infusion)
- Trail Making Test Score at 90 Days Post Infusion (Trail B)(90 days post infusion)
- The National Institutes of Health Stroke Scale (NIHSS) Score at 90 Days(90 days post infusion)
- The European Quality of Life (EQ-5D-3L) Visual Analogue Score (VAS) at 90 Days(90 days post infusion)
- Patient Health Questionnaire Scale (PHQ 8) Score at 90 Days(90 days post infusion)
- Montreal Cognitive Assessment (MoCA) Score at 90 Days Post Infusion(90 days post infusion)
- Short Form 36 Health Survey (SF-36) Scores at 90 Days Post Infusion(90 days post infusion)