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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Hematologic Malignancies

Intervention / Treatment
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* Biological: MultiStem®
* Biological: MultiStem®


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single dose Arm<br>There will be six cohorts of three patients each. Three escalating doses of MultiStem will be evaluated. | Biological: MultiStem®<br>* Patients will receive a single IV infusion of MultiStem® 2 days after HSCT.<br>|
| Experimental: Repeat Dose Arm<br>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®<br>* Patients will receive either 3 weekly IV infusions or 5 weekly infusions of MultiStem®<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum tolerated dose |  | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of grade III/IV GVHD |  | 100 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leukemia, Graft vs. Host Disease, Hematopoietic Stem Cell Transplant, Bone Marrow Transplant, Myelodysplasia