Clinical trial NCT01251952: Dose Escalation Trial of Denileukin Diftitox (Ontak) Post Autologous Transplantation
Official title: Phase I Dose Escalation Trial of Denileukin Diftitox (Ontak) Post Autologous Transplantation.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Multiple Myeloma
Lead sponsor: Barbara Ann Karmanos Cancer Institute
Sponsor class: OTHER
Collaborators: name: Eisai Inc.
First posted: 2010-12-02
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Assess Toxicities of Giving Two Doses of Ontak at Days 0 and 21 Post Autologous Stem Cell Transplantation in a Dose Escalation Fashion.
timeFrame: Up to 21 days post transplant
Secondary outcomes:
measure: 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.
timeFrame: days 0 and 21 post autologous stem cell transplantation
measure: To Evaluate the Effect of Ontak on T Cell CD4/CD8 Reconstitution Post Transplant at Each Dose.
timeFrame: days 0 and 21 post autologous stem cell transplantation
measure: To Evaluate the Effect of Ontak on Engraftment of Neutrophils and Platelets Post Transplant at Each Dose.
timeFrame: days 0 and 21 post autologous stem cell transplantation
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
Study officials:
affiliation: Barbara Ann Karmanos Cancer Institute
name: Zaid Al-Kadhimi, M.D.
role: PRINCIPAL_INVESTIGATOR
References: