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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Eisai Inc.
Information provided by:
Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT01251952
First received: November 30, 2010
Last updated: August 6, 2012
Last verified: August 2012
History of Changes
  Purpose

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:

U.S. FDA Resources

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.


Estimated Enrollment: 33
Study Start Date: November 2010
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: June 2013 (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®

  Eligibility

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

  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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01251952

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

No publications provided

Responsible Party: Zaid Al-Kadhimi, M.D., Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT01251952     History of Changes
Other Study ID Numbers: WSU 2010-039
Study First Received: November 30, 2010
Last Updated: August 6, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
 Immune System Diseases
Denileukin diftitox
Interleukin-2
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on May 23, 2013