Safety Study of MultiStem® in Patients With Acute Leukemia, Chronic Myeloid Leukemia, or Myelodysplasia

This study has been completed.
Sponsor:
Collaborator:
Cato Research
Information provided by (Responsible Party):
Athersys, Inc
ClinicalTrials.gov Identifier:
NCT00677859
First received: May 14, 2008
Last updated: January 3, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Hematologic Malignancies
Biological: MultiStem®
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Athersys, Inc:

Primary Outcome Measures:
  • maximum tolerated dose [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • incidence of grade III/IV GVHD [ Time Frame: 100 days ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: July 2008
Study Completion Date: November 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single dose Arm
There will be six cohorts of three patients each. Three escalating doses of MultiStem will be evaluated.
Biological: MultiStem®
Patients will receive a single IV infusion of MultiStem® 2 days after HSCT.
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.
Biological: MultiStem®
Patients will receive either 3 weekly IV infusions or 5 weekly infusions of MultiStem®

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00677859

Locations
United States, Arizona
Mayo Clinic Hospital
Phoenix, Arizona, United States, 85054
United States, Ohio
University Hospitals Case Medical Center
Cleveland, Ohio, United States, 44106
United States, Oregon
Oregon State University Medical Center
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Texas Transplant Institute
San Antonio, Texas, United States, 78229
Belgium
UZ Leuven
Leuven, Belgium
Sponsors and Collaborators
Athersys, Inc
Cato Research
Investigators
Principal Investigator: Richard Maziarz, MD Oregon Health and Science University
Principal Investigator: Steven Devine, MD Ohio State University
Principal Investigator: Hillard Lazarus, MD Case Western Reserve University
  More Information

No publications provided

Responsible Party: Athersys, Inc
ClinicalTrials.gov Identifier: NCT00677859     History of Changes
Other Study ID Numbers: GVHD-2007-001
Study First Received: May 14, 2008
Last Updated: January 3, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Athersys, Inc:
Leukemia
Graft vs. Host Disease
Hematopoietic Stem Cell Transplant
Bone Marrow Transplant
Myelodysplasia

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Precancerous Conditions

ClinicalTrials.gov processed this record on October 29, 2014