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

This study has been terminated.
(Drug unavailable)
Eisai Inc.
Information provided by (Responsible Party):
Zaid Al-Kadhimi, Barbara Ann Karmanos Cancer Institute Identifier:
First received: November 30, 2010
Last updated: October 25, 2013
Last verified: October 2013

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.

Condition Intervention Phase
Multiple Myeloma
Drug: Denileukin Diftitox (Ontak)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Dose Escalation Trial of Denileukin Diftitox (Ontak) Post Autologous Transplantation.

Resource links provided by NLM:

Further study details as provided by Barbara Ann Karmanos Cancer Institute:

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. [ Time Frame: Up to 21 days post transplant ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: days 0 and 21 post autologous stem cell transplantation ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    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.

Enrollment: 2
Study Start Date: November 2010
Study Completion Date: May 2013
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Denileukin Diftitox (Ontak)
Denileukin Diftitox (Ontak) administered Post Autologous Transplantation.
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.

Other Name: Ontak®


Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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.
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Please refer to this study by its identifier: NCT01251952

United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
Eisai Inc.
Principal Investigator: Zaid Al-Kadhimi, M.D. Barbara Ann Karmanos Cancer Institute
  More Information

Responsible Party: Zaid Al-Kadhimi, Principal Investigator, Barbara Ann Karmanos Cancer Institute Identifier: NCT01251952     History of Changes
Other Study ID Numbers: WSU 2010-039 
Study First Received: November 30, 2010
Results First Received: October 25, 2013
Last Updated: October 25, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Multiple Myeloma
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Neoplasms, Plasma Cell
Vascular Diseases
Denileukin diftitox
Analgesics, Non-Narcotic
Antineoplastic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Sensory System Agents processed this record on May 26, 2016