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

Hematologic Malignancies Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00677859
• Other study ID #: GVHD-2007-001
• Status: Completed
• Phase: Phase 1
• First received: May 14, 2008
• Last updated: January 3, 2012
• Start date: July 2008
• Est. completion date: November 2011

Study information

• Verified date: January 2012
• Source: Athersys, Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: November 2011
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Hematologic Malignancies
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Biological:
• MultiStem®
Patients will receive a single IV infusion of MultiStem® 2 days after HSCT.
• MultiStem®
Patients will receive either 3 weekly IV infusions or 5 weekly infusions of MultiStem®

Locations

Country	Name	City	State
Belgium	UZ Leuven	Leuven
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	Oregon State University Medical Center	Portland	Oregon
United States	Texas Transplant Institute	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Athersys, Inc	Cato Research

Countries where clinical trial is conducted

United States,  Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	maximum tolerated dose		30 days	Yes
Secondary	incidence of grade III/IV GVHD		100 days	No