Safety Study of MultiStem® in Patients With Acute Leukemia, Chronic Myeloid Leukemia, or Myelodysplasia
January 3, 2012 updated by: Athersys, Inc
A Phase I, Multicenter, Dose-Escalation Trial Evaluating Maximum-Tolerated Dose of Single and Repeated Administration of Allogeneic MultiStem® in Patients With Acute Leukemia, Chronic Myeloid Leukemia, or Myelodysplasia
The purpose of this study is to determine if MultiStem® can safely be given to patients with acute leukemia, chronic myeloid leukemia, or myelodysplasia after they have received hematopoietic stem cell transplantation.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Graft-vs.-Host
Disease (GVHD) is one of the major limitations of allogeneic hematopoietic stem cell transplants (HSCT).
This complication is major cause of morbidity and mortality and is thought to be initiated by activation of donor T-cells through recognition of "foreign" cells resident in the transplant recipient.
Acute GVHD is associated with damage to the liver, skin, gastrointestinal tract and mucosa.
Moderate to severe GVHD Grades II-IV occurs in 30-50% of matched related HSCTs and 50-70% of unrelated donor recipients.
Severe GHVD requires intense immunosuppression involving steroids and additional agents to get it under control, and patients may develop severe infections as a result of such immunosuppression.
An agent or cell therapy that could reduce the incidence and/or severity of GVHD without increasing relapse or infectious risk in HSCT patients would provide substantial benefits.
Study Type
Interventional
Enrollment (Actual)
36
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Leuven, Belgium
- UZ Leuven
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Arizona
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Phoenix, Arizona, United States, 85054
- Mayo Clinic Hospital
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Ohio
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Cleveland, Ohio, United States, 44106
- University Hospitals Case Medical Center
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Oregon
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Portland, Oregon, United States, 97239
- Oregon State University Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- University of Pennsylvania
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Texas
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San Antonio, Texas, United States, 78229
- Texas Transplant Institute
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Patients of either sex aged 18-65 years of age
- Diagnosis of acute myeloid or lymphoblastic leukemia (second or subsequent remission, if not in remission, then <20% bone marrow blasts), chronic myelogenous leukemia resistant to or intolerant of tyrosine kinase inhibitor therapy (accelerated phase, first chronic phase with TKI resistance, or second chronic phase), or myelodysplastic syndrome (intermediate/high or high risk by International Prognostic Scoring System (IPSS), lower risk by IPSS with patient having progressed after prior therapy. Complete remission is defined as the absence of blasts in the peripheral circulation at the time of enrollment and <5% blasts in the marrow within 28 days of enrollment.
- Life expectancy of at least 100 days
- Patients scheduled for allogeneic bone marrow transplant or peripheral blood stem cell transplant (PBST) procedure
- Family-related or unrelated donors
- HLA matching should either be matched related or matched unrelated donors, 6/6 match or 5/6 single allelic mismatch, with provision that the DRB1 is molecularly matched
- Performance status (ECOG ≤2)
- Signed informed consent
Exclusion Criteria:
- Active infection
- Known allergies to bovine or porcine products
- Renal function: Serum creatinine >2 mg/dL or creatinine clearance ≤50 mL/min
- Hepatic function: Screening ALT or AST ≥3x than the upper limit of normal for the laboratory OR total bilirubin ≥2.0 mg/dL (Exception: acceptable if patient is identified with pre-existing condition e.g., Gilbert's disease that will contribute to baseline elevations of bilirubin)
- Pulmonary function: FEV1, FVC, DLCO ≤50% predicted
- Cardiac function: left ventricular ejection fraction ≤50%
- Patient received an investigational agent within 30 days prior to transplant
- The patient is pregnant, has a positive serum BhCG, or is lactating
- Patient on corticosteroids at a dose >0.25 mg/kg/day
- Planned non-myeloablative transplant
- Planned cord blood transplant
- Prior allogeneic myeloablative HSCT
- HIV seropositive, HTLV seropositive, hepatitis B or C seropositive, varicella virus active infection, or syphilis active infection
- Other serious medical or psychiatric illness that, in the investigator's opinion, would not permit the patient to be managed according to the protocol
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Supportive Care
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Single dose Arm
There will be six cohorts of three patients each.
Three escalating doses of MultiStem will be evaluated.
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Patients will receive a single IV infusion of MultiStem® 2 days after HSCT.
Patients will receive either 3 weekly IV infusions or 5 weekly infusions of MultiStem®
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Experimental: Repeat Dose Arm
There will be six cohorts of three patients each.
Four dosing regimens will be evaluated,varying doses at three times weekly or five times weekly.
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Patients will receive a single IV infusion of MultiStem® 2 days after HSCT.
Patients will receive either 3 weekly IV infusions or 5 weekly infusions of MultiStem®
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
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maximum tolerated dose
Time Frame: 30 days
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30 days
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
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incidence of grade III/IV GVHD
Time Frame: 100 days
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100 days
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Hillard Lazarus, MD, Case Western Reserve University
- Principal Investigator: Richard Maziarz, MD, Oregon Health and Science University
- Principal Investigator: Steven Devine, MD, Ohio State University
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
July 1, 2008
Primary Completion (Actual)
October 1, 2011
Study Completion (Actual)
November 1, 2011
Study Registration Dates
First Submitted
May 14, 2008
First Submitted That Met QC Criteria
May 14, 2008
First Posted (Estimate)
May 15, 2008
Study Record Updates
Last Update Posted (Estimate)
January 5, 2012
Last Update Submitted That Met QC Criteria
January 3, 2012
Last Verified
January 1, 2012
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- GVHD-2007-001
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.