Dose Escalation Trial of Denileukin Diftitox (Ontak) Post Autologous Transplantation
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma
Intervention: Denileukin Diftitox (Ontak)
Intervention description: 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.
Intervention MeSH terms: Denileukin diftitox
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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:

          1. Diagnosis of Multiple Myeloma

          2. Age >=18 and no more than 70 years.

          3. Able to understand and sign a consent form.

          4. 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.

          5. Conditioning regimen to be high dose Melphalan at a dose of 200mg/m2.

          6. Karnofsky Performance Score (KPS) >60 or ECOG (Eastern Cooperative Oncology Group)
             performance status <=2

          7. Kidney function:Creatinine <2.0 mg/dl or creatinine clearance >50 ml/min

          8. Heart function: Ejection fraction >45%

          9. Liver function tests :Serum bilirubin, alanine aminotransferase (ALT), aspartate
             aminotransferase (AST) less than 3 X upper limit of normal

         10. 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:

          1. Age <18 years or > 70 years

          2. Previous exposure to denileukin diftitox.

          3. Patients with documented uncontrolled central nervous system (CNS) disease.

          4. Previous AHSCT.

          5. Significant organ dysfunction deemed to be inappropriate for autologous
             transplantation.