Clinical trial NCT00677859: Safety Study of MultiStem® in Patients With Acute Leukemia, Chronic Myeloid Leukemia, or Myelodysplasia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hematologic Malignancies
Keywords: Leukemia
Graft vs. Host Disease
Hematopoietic Stem Cell Transplant
Bone Marrow Transplant
Myelodysplasia
Lead sponsor: Healios K.K.
Sponsor class: INDUSTRY
Collaborators: name: Cato Research
First posted: 2008-05-15
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief 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.

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 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

Primary outcomes:
measure: maximum tolerated dose
timeFrame: 30 days
Secondary outcomes:
measure: incidence of grade III/IV GVHD
timeFrame: 100 days
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon State University Medical Center
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: San Antonio
country: United States
facility: Texas Transplant Institute
state: Texas
city: Leuven
country: Belgium
facility: UZ Leuven
Study officials:
affiliation: Oregon Health and Science University
name: Richard Maziarz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ohio State University
name: Steven Devine, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Case Western Reserve University
name: Hillard Lazarus, MD
role: PRINCIPAL_INVESTIGATOR
References: