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

May 26, 2017 updated by: Zaid Al-Kadhimi, Barbara Ann Karmanos Cancer Institute

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

2

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Michigan
      • Detroit, Michigan, United States, 48201-1379
        • Barbara Ann Karmanos Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Denileukin Diftitox (Ontak)
Denileukin Diftitox (Ontak) administered Post Autologous Transplantation.

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.

Other Names:
  • Ontak®

What is the study measuring?

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.
Time Frame: Up to 21 days post transplant
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.
Time Frame: days 0 and 21 post autologous stem cell transplantation
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.
Time Frame: days 0 and 21 post autologous stem cell transplantation
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.
Time Frame: 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.
days 0 and 21 post autologous stem cell transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2010

Primary Completion (Actual)

July 1, 2011

Study Completion (Actual)

May 1, 2013

Study Registration Dates

First Submitted

November 30, 2010

First Submitted That Met QC Criteria

November 30, 2010

First Posted (Estimate)

December 2, 2010

Study Record Updates

Last Update Posted (Actual)

June 20, 2017

Last Update Submitted That Met QC Criteria

May 26, 2017

Last Verified

May 1, 2017

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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