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

Primary Purpose

Multiple Myeloma

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Denileukin Diftitox (Ontak)
Sponsored by
Barbara Ann Karmanos Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Barbara Ann Karmanos Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Denileukin Diftitox (Ontak)

Arm Description

Denileukin Diftitox (Ontak) administered Post Autologous Transplantation.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
To Evaluate the Effect of Ontak on T Cell CD4/CD8 Reconstitution Post Transplant at Each Dose.
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.

Full Information

First Posted
November 30, 2010
Last Updated
May 26, 2017
Sponsor
Barbara Ann Karmanos Cancer Institute
Collaborators
Eisai Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01251952
Brief Title
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

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Terminated
Why Stopped
Drug unavailable
Study Start Date
November 2010 (undefined)
Primary Completion Date
July 2011 (Actual)
Study Completion Date
May 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Barbara Ann Karmanos Cancer Institute
Collaborators
Eisai Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Denileukin Diftitox (Ontak)
Arm Type
Experimental
Arm Description
Denileukin Diftitox (Ontak) administered Post Autologous Transplantation.
Intervention Type
Drug
Intervention Name(s)
Denileukin Diftitox (Ontak)
Other Intervention Name(s)
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.
Primary Outcome Measure Information:
Title
Assess Toxicities of Giving Two Doses of Ontak at Days 0 and 21 Post Autologous Stem Cell Transplantation in a Dose Escalation Fashion.
Description
After drug infusion, participants will be closely monitored for at least 4 hours for side effects
Time Frame
Up to 21 days post transplant
Secondary Outcome Measure Information:
Title
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
Title
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
Title
To Evaluate the Effect of Ontak on Engraftment of Neutrophils and Platelets Post Transplant at Each Dose.
Description
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.
Time Frame
days 0 and 21 post autologous stem cell transplantation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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: Diagnosis of Multiple Myeloma Age >=18 and no more than 70 years. Able to understand and sign a consent form. 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. Conditioning regimen to be high dose Melphalan at a dose of 200mg/m2. Karnofsky Performance Score (KPS) >60 or ECOG (Eastern Cooperative Oncology Group) performance status <=2 Kidney function:Creatinine <2.0 mg/dl or creatinine clearance >50 ml/min Heart function: Ejection fraction >45% Liver function tests :Serum bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) less than 3 X upper limit of normal 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: Age <18 years or > 70 years Previous exposure to denileukin diftitox. Patients with documented uncontrolled central nervous system (CNS) disease. Previous AHSCT. Significant organ dysfunction deemed to be inappropriate for autologous transplantation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zaid Al-Kadhimi, M.D.
Organizational Affiliation
Barbara Ann Karmanos Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Barbara Ann Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201-1379
Country
United States

12. IPD Sharing Statement

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

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