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

Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01251952
• Other study ID #: WSU 2010-039
• Status: Terminated
• Phase: Phase 1
• First received: November 30, 2010
• Last updated: October 25, 2013
• Start date: November 2010
• Est. completion date: May 2013

Study information

• Verified date: October 2013
• Source: Barbara Ann Karmanos Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: May 2013
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma

Intervention

Drug:
• Denileukin Diftitox (Ontak)
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.

Locations

Country	Name	City	State
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Barbara Ann Karmanos Cancer Institute	Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No