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

Phase 1

Terminated

• Conditions: Multiple Myeloma
• Interventions: Drug: Denileukin Diftitox (Ontak)

• Registration Number: NCT01251952
• Lead Sponsor: Barbara Ann Karmanos Cancer Institute

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-11
• Study First Submitted: 2010-11-30
• Study First Submitted QC: 2010-11-30
• Study First Posted: 2010-12-02
• Primary Completion: 2011-07
• Study Completion: 2013-05
• Results First Submitted: 2013-10-25
• Results First Submitted QC: 2013-10-25
• Results First Posted: 2013-12-16
• Status Verified: 2017-05
• Last Update Submitted: 2017-05-26
• Last Update Posted: 2017-06-20

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

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

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Denileukin Diftitox (Ontak)	Denileukin Diftitox (Ontak)	Denileukin Diftitox (Ontak) administered Post Autologous Transplantation.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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 Engraftment of Neutrophils and Platelets Post Transplant at Each Dose.	days 0 and 21 post autologous stem cell transplantation	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.
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

Trial Locations

Locations (1)

Barbara Ann Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States