Dose Escalation Trial of Denileukin Diftitox (Ontak) Post Autologous Transplantation

Study Overview
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Brief Summary
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The primary goal of this study is to determine the feasibility and safety of giving two doses of denileukin diftitox (DD) at days 0 and 21 post autologous stem cell transplantation in a dose escalation fashion. Secondary goals include evaluating the the effect of DD on the number and percentage of T-regs in the peripheral blood post transplant at each dose level, the effect of DD on T cell (CD4/CD8) reconstitution post transplant at each dose level and determining the time to engraftment: absolute neutrophil count (>0.5 x 10^9/L for 3 consecutive days), and platelet (>20X 10^9/L for 3 consecutive days). The hypothesis for the study is based on the ability of DD to deplete T-regs and subsequently enhance the immune reconstitution and reverse post transplant lymphopenia. This may indirectly enhance the efficacy of autologous transplantation and reduce disease relapse.

Official Title
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Phase I Dose Escalation Trial of Denileukin Diftitox (Ontak) Post Autologous Transplantation.

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Denileukin Diftitox (Ontak)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients age > =18 who have been diagnosed with Multiple Myeloma and are scheduled for autologous peripheral blood hematopoietic stem cell transplant (AHSCT) will be screened for eligibility. Patients must fulfill all of the following inclusion criteria to be eligible for this study: Diagnosis of Multiple Myeloma Age >=18 and no more than 70 years. Able to understand and sign a consent form. Can collect peripheral blood stem cells with a CD34+ cell dose of at least 5.0 x 106/kg. The CD34 molecule is a Cluster of Differentiation molecule present on hematopoietic stem cells. Conditioning regimen to be high dose Melphalan at a dose of 200mg/m2. Karnofsky Performance Score (KPS) >60 or ECOG (Eastern Cooperative Oncology Group) performance status <=2 Kidney function:Creatinine <2.0 mg/dl or creatinine clearance >50 ml/min Heart function: Ejection fraction >45% Liver function tests :Serum bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) less than 3 X upper limit of normal Lung function tests: Forced Vital Capacity (FVC), Forced Expiratory Volume in One Second (FEV1) or Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) >45% predicted Exclusion Criteria: Age <18 years or > 70 years Previous exposure to denileukin diftitox. Patients with documented uncontrolled central nervous system (CNS) disease. Previous AHSCT. Significant organ dysfunction deemed to be inappropriate for autologous transplantation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Denileukin Diftitox (Ontak)<br>Denileukin Diftitox (Ontak) administered Post Autologous Transplantation. | Drug: Denileukin Diftitox (Ontak)<br>* After receiving their stem cell transplant on Day 0, participants will receive study agent via a 30 minute infusion. Participants will also receive a 30 minute infusion of study agent on Day 21. Follow-up visits for clinical assessment, blood draws for routine clinical laboratory studies and for immuno-correlative studies will also take place on days 42, 90, 180 and 360.<br>* Other names: Ontak®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess Toxicities of Giving Two Doses of Ontak at Days 0 and 21 Post Autologous Stem Cell Transplantation in a Dose Escalation Fashion. | After drug infusion, participants will be closely monitored for at least 4 hours for side effects | Up to 21 days post transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Evaluate the Effect of Ontak on the Number and Percentage of Regulatory T Cells in the Peripheral Blood Post Transplant at Each Dose Level. |  | days 0 and 21 post autologous stem cell transplantation | 
| To Evaluate the Effect of Ontak on T Cell CD4/CD8 Reconstitution Post Transplant at Each Dose. |  | days 0 and 21 post autologous stem cell transplantation | 
| To Evaluate the Effect of Ontak on Engraftment of Neutrophils and Platelets Post Transplant at Each Dose. | During hospitalization stay (approximately 2 weeks), participants will receive injections of G-CSF on a daily basis starting on Day 6 and ending when white blood cells have engrafted. Participants usually remain hospitalized until engraftment. | days 0 and 21 post autologous stem cell transplantation |